Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for Hospitalized Adult Patients With COVID-19
Sponsor
Regeneron Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT04426695
Collaborator
(none)
2,252
123
4
16.4
18.3
1.1
Study Details
Study Description
Brief Summary
The primary objectives are:
Pooled Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)
-
To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2
-
To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
Phase 1/2 (Cohort 1)
-
To exclude futility of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
-
To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
2252 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Phase 1/Phase 2/Phase 3Phase 1/Phase 2/Phase 3
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19
Actual Study Start Date
:
Jun 11, 2020
Actual Primary Completion Date
:
May 7, 2021
Actual Study Completion Date
:
Oct 22, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: On Low-Flow Oxygen Cohort 1 (C1): O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device |
Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo
Placebo IV Single Dose
|
| Experimental: With COVID-19 symptoms but not requiring supplemental O2 Cohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen |
Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo
Placebo IV Single Dose
|
| Experimental: High O2 No Mechanical Ventilation Cohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation |
Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo
Placebo IV Single Dose
|
| Experimental: On Mechanical Ventilation Cohort 3 (C3): On mechanical ventilation |
Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
Drug: Placebo
Placebo IV Single Dose
|
Outcome Measures
Primary Outcome Measures
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Based on Seronegative mFAS [Day 1 to Day 7]
Time-weighted average daily change from Day 1 to Day 7 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on High Viral Load mFAS [Day 6 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Seronegative mFAS [Day 6 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Overall mFAS [Day 6 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on High Viral Load mFAS [Day 1 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS [Day 1 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Overall mFAS [Day 1 to Day 29]
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.
- Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events [Up to Day 169]
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the observation period.
- Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 [Up to Day 4]
Infusion-related reactions are defined as any relevant adverse event that occurs during the infusion or up to day 4. The severity of adverse events (including test findings classified as adverse events) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
- Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 [Up to Day 29]
Hypersensitivity reactions are defined as any relevant adverse event that occurs during the infusion or up to study day 29. The severity of adverse events (including test findings classified as adverse events) were graded according to NCI-CTCAE.
- Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS [Up to Day 29]
Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS [Up to Day 29]
Cumulative incidence percentage was estimated using Kaplan-Meier method.
Secondary Outcome Measures
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [by Day 29]
Percentage of participants who went on mechanical ventilation by Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants who went on mechanical ventilation at Day 29 based on Seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on High Viral Load mFAS [Day 6 to Day 29]
Percentage of participants who died from Day 6 through Day 29 based on high viral load mFAS were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS [Day 6 to Day 29]
Percentage of participants who died from Day 6 through Day 29 Based on seronegative mFAS in pooled analysis phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on High Viral Load mFAS [Day 1 to Day 29]
Percentage of participants who died from Day 1 through Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS [Day 1 to Day 29]
Percentage of participants who died from Day 1 through Day 29 based on seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS [by Day 29]
Percentage of participants who were discharged by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants who were discharged by Day 29 based on seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS [Up to Day 29]
Percentage of participants who died or were readmitted to hospital over time based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)were reported. Readmission to hospital was based on investigator report.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants who died or were readmitted to hospital at Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Readmission to hospital was based on investigator report.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on High Viral Load mFAS [by Day 29]
Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on Seronegative mFAS [by Day 29]
Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A)were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [by Day 29]
Number of participants with cumulative incidence of mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants with cumulative incidence of mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [by Day 29]
Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on High Viral Load mFAS [Up to Day 56]
Time to discharge from hospital based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS [Up to Day 56]
Time to discharge from hospital based on Seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Treatment-Emergent Serious Adverse Events [Up to Day 169]
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 [Up to Day 4]
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 [Up to Day 29]
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS [Day 6 to Day 29]
Percentage of participants who died from Day 6 through Day 29 in phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS [Day 1 to Day 29]
Percentage of participants who died from Day 1 through Day 29 in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants who were discharged in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS [Up to Day 29]
Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) by Day 29 were reported. Readmission to hospital was based on investigator report.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death up to Day 29 Based on Seronegative mFAS [Up to Day 29]
Percentage of participants with cumulative incidence of death in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) up to Day 29 from randomization were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants with cumulative incidence of mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS [by Day 29]
Percentage of participants with cumulative incidence of death or mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS [Up to Day 56]
Time to discharge from hospital up to Day 56 was reported.
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 11 Based on Seronegative mFAS [Day 1 to Day 11]
TWA change from baseline in viral load up to Day 11 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 11, was measured by RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 29 [Day 1 to Day 29]
TWA change from baseline in viral load up to Day 29 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 29, was measured by quantitative RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time [Days 3, 5, 7, 9, 11, 13, 15, 22 and 29]
Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Percent Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time [Days 3, 5, 7, 9, 11, 13, 15, 22 and 29]
Percent change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [by Day 29]
Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 to Day 29 Based on High Viral Load mFAS [Day 6 to Day 29]
Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 to Day 29 Based on High Viral Load mFAS [Day 1 to Day 29]
Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS [by Day 29]
Percentage of participants who were discharged in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS [Up to Day 29]
Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) over time were reported. Readmission to hospital was based on investigator report.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death Over Time Based on High Viral Load mFAS [Up to Day 29]
Cumulative Incidence of Death Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation Over Time Based on High Viral Load mFAS [Up to Day 29]
Cumulative Incidence of Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation Over Time Based on High Viral Load mFAS [Up to Day 29]
Cumulative Incidence of Death or Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS [Up to Day 56]
Time to Discharge in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Over Time Based on Seronegative mFAS [Up to Day 29]
Time-weighted average daily change over time up to Day 29 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Change From Baseline as Measured by RT-qPCR in NP Swabs Over Time Based on Seronegative mFAS [Days 3, 5, 7, 9, 11, 13, 15, 22 and 29]
Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on Seronegative mFAS [Through Day 29]
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [Through Day 29]
- Phase 1 [Cohort 1]: Area Under the Concentration-Time Curve From Time 0 to 28 Days Post-dose (AUC0-28) [Up to Day 28]
- Concentration at the End of Infusion (Ceoi) [Day 1]
- Concentration at Day 28 (C28) [Day 28]
- Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 [Through Day 169]
- Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 [Through Day 169]
- Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10933 [Through Day 57]
- Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10987 [Through Day 57]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization and no alternative explanation for current clinical condition. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable.
-
Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤10 days before randomization
-
Hospitalized for ≤72 hours with at least 1 of the following at randomization; patients meeting more than one criterion will be categorized in the most severely affected category:
-
Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen
-
Cohort 1: Maintains O2 saturation >93% on low-flow oxygen as defined in the protocol
-
Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
-
Cohort 3: On mechanical ventilation
Key Exclusion Criteria:
-
Phase 1 Only: Patients maintaining O2 saturation >94% on room air
-
In the opinion of the investigator, unlikely to survive for >48 hours from screening
-
Receiving extracorporeal membrane oxygenation (ECMO)
-
Has new-onset stroke or seizure disorder during hospitalization
-
Initiated on renal replacement therapy due to COVID-19
NOTE: Other protocol defined inclusion / exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regeneron Study Site | Birmingham | Alabama | United States | 35249 |
| 2 | Regeneron Study Site | Chandler | Arizona | United States | 85224 |
| 3 | Regeneron Study Site | Phoenix | Arizona | United States | 85006 |
| 4 | Regeneron Study Site 1 | Tucson | Arizona | United States | 85724 |
| 5 | Regeneron Study Site | Long Beach | California | United States | 90806 |
| 6 | Regeneron Study Site | Mission Hills | California | United States | 91345 |
| 7 | Regeneron Study Site | Sacramento | California | United States | 95817 |
| 8 | Regeneron Study Site | Santa Monica | California | United States | 90404 |
| 9 | Regeneron Study Site | Stanford | California | United States | 94305 |
| 10 | Regeneron Study Site | Aurora | Colorado | United States | 80045 |
| 11 | Regeneron Study Site | Boca Raton | Florida | United States | 33486 |
| 12 | Regeneron Study Site | Fort Pierce | Florida | United States | 34982 |
| 13 | Regeneron Study Site | Gainesville | Florida | United States | 32610 |
| 14 | Regeneron Study Site | Orlando | Florida | United States | 32803 |
| 15 | Regeneron Study Site | Pensacola | Florida | United States | 32504 |
| 16 | Regeneron Study Site | Sarasota | Florida | United States | 34239 |
| 17 | Regeneron Study Site | Tampa | Florida | United States | 33612 |
| 18 | Regeneron Study Site | Atlanta | Georgia | United States | 30309 |
| 19 | Regeneron Study Site | Atlanta | Georgia | United States | 30322 |
| 20 | Regeneron Study Site | Augusta | Georgia | United States | 30912 |
| 21 | Regeneron Study Site | Marietta | Georgia | United States | 30060 |
| 22 | Regeneron Study Site | Chicago | Illinois | United States | 60611 |
| 23 | Regeneron Study Site | Chicago | Illinois | United States | 60612 |
| 24 | Regeneron Study Site | Glenview | Illinois | United States | 60026 |
| 25 | Regeneron Study Site | Urbana | Illinois | United States | 61801 |
| 26 | Regeneron Study Site | Indianapolis | Indiana | United States | 46260 |
| 27 | Regeneron Study Site | Iowa City | Iowa | United States | 52242 |
| 28 | Regeneron Study Site | Louisville | Kentucky | United States | 40202 |
| 29 | Regeneron Study Site | Louisville | Kentucky | United States | 40217 |
| 30 | Regeneron Study Site | New Orleans | Louisiana | United States | 70112 |
| 31 | Regeneron Study Site | New Orleans | Louisiana | United States | 70122 |
| 32 | Regeneron Study Site | Baltimore | Maryland | United States | 21201 |
| 33 | Regeneron Study Site | Boston | Massachusetts | United States | 02111 |
| 34 | Regeneron Study Site | Boston | Massachusetts | United States | 02115 |
| 35 | Regeneron Study Site | Boston | Massachusetts | United States | 02118 |
| 36 | Regeneron Study Site | Grand Rapids | Michigan | United States | 49503 |
| 37 | Regeneron Study Site | Royal Oak | Michigan | United States | 48073 |
| 38 | Regeneron Study Site | Rochester | Minnesota | United States | 55905 |
| 39 | Regeneron Study Site | Chesterfield | Missouri | United States | 63017 |
| 40 | Regeneron Study Site | Saint Louis | Missouri | United States | 63104 |
| 41 | Regeneron Study Site | Saint Louis | Missouri | United States | 63110 |
| 42 | Regeneron Study Site | Omaha | Nebraska | United States | 68198-5400 |
| 43 | Regeneron Study Site | Las Vegas | Nevada | United States | 89109 |
| 44 | Regeneron Study Site | Englewood | New Jersey | United States | 07631 |
| 45 | Regeneron Study Site | Hackensack | New Jersey | United States | 07601 |
| 46 | Regeneron Study Site | Morristown | New Jersey | United States | 07960 |
| 47 | Regeneron Study Site | Neptune | New Jersey | United States | 07753 |
| 48 | Regeneron Study Site | Pennington | New Jersey | United States | 08534 |
| 49 | Regeneron Study Site | Summit | New Jersey | United States | 07901 |
| 50 | Regeneron Study Site | Teaneck | New Jersey | United States | 07666 |
| 51 | Regeneron Study Site | Albuquerque | New Mexico | United States | 87108 |
| 52 | Regeneron Study Site | Bronx | New York | United States | 10451 |
| 53 | Regeneron Study Site | Bronx | New York | United States | 10461 |
| 54 | Regeneron Study Site | Brooklyn | New York | United States | 11219 |
| 55 | Regeneron Study Site | Buffalo | New York | United States | 14203 |
| 56 | Regeneron Study Site 1 | Buffalo | New York | United States | 14215 |
| 57 | Regeneron Study Site 2 | Buffalo | New York | United States | 14215 |
| 58 | Regeneron Study Site | Jamaica | New York | United States | 11432 |
| 59 | Regeneron Study Site | New York | New York | United States | 10003 |
| 60 | Regeneron Study Site | New York | New York | United States | 10019 |
| 61 | Regeneron Study Site | New York | New York | United States | 10025 |
| 62 | Regeneron Study Site | New York | New York | United States | 10029 |
| 63 | Regeneron Study Site | New York | New York | United States | 10032 |
| 64 | Regeneron Study Site | New York | New York | United States | 10037 |
| 65 | Regeneron Study Site | Rochester | New York | United States | 14642 |
| 66 | Regeneron Study Site | Syracuse | New York | United States | 13210 |
| 67 | Regeneron Study Site | West Islip | New York | United States | 11795 |
| 68 | Regeneron Study Site | White Plains | New York | United States | 10601 |
| 69 | Regeneron Study Site | Chapel Hill | North Carolina | United States | 27599 |
| 70 | Regeneron Study Site | Greensboro | North Carolina | United States | 27408 |
| 71 | Regeneron Study Site | Columbus | Ohio | United States | 43210 |
| 72 | Regeneron Study Site | Columbus | Ohio | United States | 43215 |
| 73 | Regeneron Study Site | Dayton | Ohio | United States | 45409 |
| 74 | Regeneron Study Site | Portland | Oregon | United States | 97213 |
| 75 | Regeneron Study Site | Portland | Oregon | United States | 97239 |
| 76 | Regeneron Study Site | Philadelphia | Pennsylvania | United States | 19140 |
| 77 | Regeneron Study Site | Providence | Rhode Island | United States | 02903 |
| 78 | Regeneron Study Site | Providence | Rhode Island | United States | 02906 |
| 79 | Regeneron Study Site | Sioux Falls | South Dakota | United States | 57108 |
| 80 | Regeneron Study Site 1 | Amarillo | Texas | United States | 79106 |
| 81 | Regeneron Study Site 2 | Amarillo | Texas | United States | 79106 |
| 82 | Regeneron Study Site | Dallas | Texas | United States | 75235 |
| 83 | Regeneron Study Site | Dallas | Texas | United States | 75246 |
| 84 | Regeneron Study Site | Dallas | Texas | United States | 75390 |
| 85 | Regeneron Study Site | Houston | Texas | United States | 77004 |
| 86 | Regeneron Study Site | Houston | Texas | United States | 77024 |
| 87 | Regeneron Study Site | Houston | Texas | United States | 77030 |
| 88 | Regeneron Study Site | Lubbock | Texas | United States | 79410 |
| 89 | Regeneron Study Site | Sugar Land | Texas | United States | 77479 |
| 90 | Regeneron Study Site | Tyler | Texas | United States | 75701 |
| 91 | Regeneron Study Site | Murray | Utah | United States | 84107 |
| 92 | Regeneron Study Site | Salt Lake City | Utah | United States | 84143 |
| 93 | Regeneron Study Site | Richmond | Virginia | United States | 23298 |
| 94 | Regeneron Study Site | Everett | Washington | United States | 98201 |
| 95 | Regeneron Study Site 1 | Seattle | Washington | United States | 98122 |
| 96 | Regeneron Study Site | Madison | Wisconsin | United States | 53792 |
| 97 | Regeneron Study Site | Salvador | Bahia | Brazil | 40170-130 |
| 98 | Regeneron Study Site | Fortaleza | Ceara | Brazil | 60160-230 |
| 99 | Regeneron Study Site | Curitiba | Paraná | Brazil | 80810-040 |
| 100 | Regeneron Study Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 |
| 101 | Regeneron Study Site | Passo Fundo | RS | Brazil | 99010-170 |
| 102 | Regeneron Study Site | Chapeco | Santa Catarina | Brazil | 89801-355 |
| 103 | Regeneron Study Site | Criciuma | Santa Catarina | Brazil | 88811-508 |
| 104 | Regeneron Study Site | Botucatu | Sao Paolo | Brazil | 18618-686 |
| 105 | Regeneron Study Site | Campinas | Sao Paolo | Brazil | 13060-080 |
| 106 | Regeneron Study Site | São Paulo | Brazil | 02401- 400 | |
| 107 | Regeneron Study Site | São Paulo | Brazil | 04012-909 | |
| 108 | Regeneron Study Site | São Paulo | Brazil | 05403-010 | |
| 109 | Regeneron Study Site 1 | Las Condes | Santiago De Chile | Chile | 7591047 |
| 110 | Regeneron Study Site 2 | Las Condes | Santiago De Chile | Chile | 7591047 |
| 111 | Regeneron Study Site | Vitacura | Santiago De Chile | Chile | 7650568 |
| 112 | Regeneron Study Site | Santiago de Chile | Chile | 7500691 | |
| 113 | Regeneron Study Site | Guadalajara | Jalisco | Mexico | 44340 |
| 114 | Regeneron Study Site | Monterrey | Nuevo Leon | Mexico | 64718 |
| 115 | Regeneron Study Site | Culiacán | Sinaloa | Mexico | 80020 |
| 116 | Regeneron Study Site | Culiacan | Mexico | 80230 | |
| 117 | Regeneron Study Site | Monterrey | Mexico | 64060 | |
| 118 | Regeneron Study Site 1 | Mérida | Mexico | 97000 | |
| 119 | Regeneron Study Site 2 | Mérida | Mexico | 97000 | |
| 120 | Regeneron Study Site | Veracruz | Mexico | 91700 | |
| 121 | Regeneron Study Site | Zapopan | Mexico | 45170 | |
| 122 | Regeneron Study Site | Chisinau | Moldova, Republic of | MD-2025 | |
| 123 | Regeneron Study Site | Bucuresti | Romania | 021105 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04426695
Other Study ID Numbers:
- R10933-10987-COV-2066
- 2020-002537-15
First Posted:
Jun 11, 2020
Last Update Posted:
Jul 25, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Regeneron Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 2324 participants were screened and 2203 participants randomized and treated, 49 participants were randomized but not treated, and 72 discontinued at the screening phase. Reasons for discontinuation at screening phase: 54 - Screen Failure, 10 - Subject Decision, 1- Sponsor Request, 7- Other. |
| Arm/Group Title | Phase 1: Cohort 1 (Placebo) | Phase 1: Cohort 1 (R10933+R10987 2400 mg IV) | Phase 1: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 1 (Placebo) | Phase 2: Cohort 1 (R10933+R10987 2400 mg | Phase 2: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 3: Cohort 1 (Placebo) | Phase 3: Cohort 1 (R10933+R10987 2400 mg) | Phase 3: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 1A (Placebo) | Phase 2: Cohort 1A (R10933+R10987 2400 mg IV) | Phase 2: Cohort 1A (R10933+R10987 8000 mg IV) | Phase 2: Cohort 2 (Placebo) | Phase 2: Cohort 2 (R10933+R10987 2400 mg IV) | Phase 2: Cohort 2 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 3 (Placebo) | Phase 2: Cohort 3 (R10933+R10987 2400 mg IV) | Phase 2: Cohort 3 (R10933+R10987 8000 mg IV) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 milligrams (mg) intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 milligrams (mg) intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 milligrams (mg) intravenously on Day 1 in Phase 3 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 3 (Cohort 1) | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 3). |
| Period Title: Overall Study | ||||||||||||||||||
| STARTED | 21 | 19 | 20 | 208 | 211 | 210 | 251 | 252 | 252 | 201 | 205 | 203 | 52 | 58 | 54 | 12 | 12 | 11 |
| Treated | 18 | 18 | 20 | 204 | 206 | 205 | 247 | 246 | 246 | 198 | 202 | 197 | 51 | 56 | 54 | 12 | 12 | 11 |
| COMPLETED | 13 | 12 | 16 | 146 | 153 | 148 | 186 | 195 | 189 | 157 | 165 | 166 | 33 | 28 | 31 | 5 | 4 | 7 |
| NOT COMPLETED | 8 | 7 | 4 | 62 | 58 | 62 | 65 | 57 | 63 | 44 | 40 | 37 | 19 | 30 | 23 | 7 | 8 | 4 |
Baseline Characteristics
| Arm/Group Title | Phase 1: Cohort 1 (Placebo) | Phase 1: Cohort 1 (R10933+R10987 2400 mg IV) | Phase 1: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 1 (Placebo) | Phase 2: Cohort 1 (R10933+R10987 2400 mg IV) | Phase 2: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 3: Cohort 1 (Placebo) | Phase 3: Cohort 1 (R10933+R10987 2400 mg IV) | Phase 3: Cohort 1 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 1A (Placebo) | Phase 2: Cohort 1A (R10933+R10987 2400 mg IV) | Phase 2: Cohort 1A (R10933+R10987 8000 mg IV) | Phase 2: Cohort 2 (Placebo) | Phase 2: Cohort 2 (R10933+R10987 2400 mg IV) | Phase 2: Cohort 2 (R10933+R10987 8000 mg IV) | Phase 2: Cohort 3 (Placebo) | Phase 2: Cohort 3 (R10933+R10987 2400 mg IV) | Phase 2: Cohort 3 (R10933+R10987 8000 mg IV) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 1 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 1 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 1 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1) | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1). | Phase 1: Cohort 1 (R10933+R10987 2400 mg IV)Edit Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 3 (Cohort 1) | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Total of all reporting groups |
| Overall Participants | 18 | 18 | 20 | 204 | 206 | 205 | 247 | 246 | 246 | 198 | 202 | 197 | 51 | 56 | 54 | 12 | 12 | 11 | 2203 |
| Age, Customized (Count of Participants) | |||||||||||||||||||
| Age: 18- <40 years |
1
5.6%
|
1
5.6%
|
2
10%
|
26
12.7%
|
16
7.8%
|
17
8.3%
|
29
11.7%
|
28
11.4%
|
14
5.7%
|
22
11.1%
|
20
9.9%
|
20
10.2%
|
4
7.8%
|
4
7.1%
|
6
11.1%
|
0
0%
|
1
8.3%
|
1
9.1%
|
212
9.6%
|
| Age: 40- <65 years |
9
50%
|
8
44.4%
|
10
50%
|
82
40.2%
|
99
48.1%
|
96
46.8%
|
105
42.5%
|
119
48.4%
|
127
51.6%
|
82
41.4%
|
101
50%
|
91
46.2%
|
30
58.8%
|
23
41.1%
|
24
44.4%
|
6
50%
|
4
33.3%
|
5
45.5%
|
1021
46.3%
|
| Age: >=65 years |
8
44.4%
|
9
50%
|
8
40%
|
96
47.1%
|
91
44.2%
|
92
44.9%
|
113
45.7%
|
99
40.2%
|
105
42.7%
|
94
47.5%
|
81
40.1%
|
86
43.7%
|
17
33.3%
|
29
51.8%
|
24
44.4%
|
6
50%
|
7
58.3%
|
5
45.5%
|
970
44%
|
| Sex: Female, Male (Count of Participants) | |||||||||||||||||||
| Female |
8
44.4%
|
8
44.4%
|
10
50%
|
90
44.1%
|
98
47.6%
|
98
47.8%
|
113
45.7%
|
112
45.5%
|
115
46.7%
|
91
46%
|
87
43.1%
|
89
45.2%
|
17
33.3%
|
20
35.7%
|
20
37%
|
8
66.7%
|
4
33.3%
|
2
18.2%
|
990
44.9%
|
| Male |
10
55.6%
|
10
55.6%
|
10
50%
|
114
55.9%
|
108
52.4%
|
107
52.2%
|
134
54.3%
|
134
54.5%
|
131
53.3%
|
107
54%
|
115
56.9%
|
108
54.8%
|
34
66.7%
|
36
64.3%
|
34
63%
|
4
33.3%
|
8
66.7%
|
9
81.8%
|
1213
55.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||||||||||
| Hispanic or Latino |
12
66.7%
|
7
38.9%
|
10
50%
|
49
24%
|
50
24.3%
|
52
25.4%
|
92
37.2%
|
94
38.2%
|
82
33.3%
|
38
19.2%
|
53
26.2%
|
40
20.3%
|
13
25.5%
|
22
39.3%
|
18
33.3%
|
6
50%
|
5
41.7%
|
4
36.4%
|
647
29.4%
|
| Not Hispanic or Latino |
6
33.3%
|
11
61.1%
|
10
50%
|
144
70.6%
|
148
71.8%
|
146
71.2%
|
146
59.1%
|
140
56.9%
|
155
63%
|
148
74.7%
|
138
68.3%
|
143
72.6%
|
35
68.6%
|
33
58.9%
|
30
55.6%
|
6
50%
|
7
58.3%
|
7
63.6%
|
1453
66%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
11
5.4%
|
8
3.9%
|
7
3.4%
|
9
3.6%
|
12
4.9%
|
9
3.7%
|
12
6.1%
|
11
5.4%
|
14
7.1%
|
3
5.9%
|
1
1.8%
|
6
11.1%
|
0
0%
|
0
0%
|
0
0%
|
103
4.7%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
0.5%
|
1
0.5%
|
2
1%
|
9
3.6%
|
9
3.7%
|
13
5.3%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
36
1.6%
|
| Asian |
0
0%
|
2
11.1%
|
0
0%
|
6
2.9%
|
7
3.4%
|
6
2.9%
|
6
2.4%
|
10
4.1%
|
9
3.7%
|
11
5.6%
|
8
4%
|
6
3%
|
2
3.9%
|
2
3.6%
|
1
1.9%
|
1
8.3%
|
1
8.3%
|
0
0%
|
78
3.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
2
1%
|
1
0.5%
|
1
0.5%
|
0
0%
|
1
0.4%
|
1
0.4%
|
0
0%
|
0
0%
|
1
0.5%
|
1
2%
|
1
1.8%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
10
0.5%
|
| Black or African American |
3
16.7%
|
2
11.1%
|
8
40%
|
34
16.7%
|
21
10.2%
|
33
16.1%
|
26
10.5%
|
32
13%
|
25
10.2%
|
27
13.6%
|
32
15.8%
|
25
12.7%
|
7
13.7%
|
6
10.7%
|
9
16.7%
|
1
8.3%
|
1
8.3%
|
3
27.3%
|
295
13.4%
|
| White |
12
66.7%
|
11
61.1%
|
11
55%
|
136
66.7%
|
146
70.9%
|
134
65.4%
|
159
64.4%
|
151
61.4%
|
158
64.2%
|
111
56.1%
|
116
57.4%
|
131
66.5%
|
33
64.7%
|
39
69.6%
|
36
66.7%
|
8
66.7%
|
9
75%
|
5
45.5%
|
1406
63.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
3
16.7%
|
3
16.7%
|
1
5%
|
25
12.3%
|
30
14.6%
|
29
14.1%
|
47
19%
|
43
17.5%
|
40
16.3%
|
49
24.7%
|
46
22.8%
|
34
17.3%
|
7
13.7%
|
8
14.3%
|
8
14.8%
|
1
8.3%
|
1
8.3%
|
3
27.3%
|
378
17.2%
|
Outcome Measures
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Based on Seronegative mFAS |
|---|---|
| Description | Time-weighted average daily change from Day 1 to Day 7 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. |
| Time Frame | Day 1 to Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative modified full analysis set (mFAS) was defined as all participants in mFAS with documented seronegative status at the baseline. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 131 | 150 | 160 | 310 |
| Least Squares Mean (Standard Error) [log10 copies/milliliter (mL)] |
-1.03
(0.10)
|
-1.28
(0.09)
|
-1.34
(0.09)
|
-1.31
(0.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0663 |
| Comments | P-value for change from baseline on log scale for each treatment group was based on the Analysis of covariance (ANCOVA) model with treatment group. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 0.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0204 |
| Comments | P-value for change from baseline on log scale for each treatment group was based on the Analysis of covariance (ANCOVA) model with treatment group. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
() 95% -0.57 to 0.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0172 |
| Comments | P-value for change from baseline on log scale for each treatment group was based on the Analysis of covariance (ANCOVA) model with treatment group. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to -0.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 211 | 220 | 225 | 445 |
| Number (95% Confidence Interval) [Percentage of Participants] |
13.3
73.9%
|
7.3
40.6%
|
12.4
62%
|
9.9
4.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0431 |
| Comments | P-value was derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7975 |
| Comments | P-value was derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2048 |
| Comments | P-value was derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 147 | 162 | 179 | 341 |
| Number (95% Confidence Interval) [Percentage of Participants] |
15.0
83.3%
|
4.9
27.2%
|
10.6
53%
|
7.9
3.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0039 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2415 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0195 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Overall mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mFAS included all FAS participants with a positive SARS-CoV-2 RT-qPCR conducted in the central laboratory in NP swab samples at randomization. Analysis based on treatment allocated (as randomized). "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 367 | 387 | 383 | 770 |
| Number (95% Confidence Interval) [Percentage of Participants] |
10.6
58.9%
|
5.4
30%
|
10.7
53.5%
|
8.1
4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0085 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9902 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1486 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Number (95% Confidence Interval) [Percentage of Participants] |
18.8
104.4%
|
10.0
55.6%
|
14.4
72%
|
12.2
6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0092 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2210 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0249 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Number (95% Confidence Interval) [Percentage of Participants] |
19.4
107.8%
|
8.1
45%
|
12.2
61%
|
10.3
5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0045 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0714 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0061 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Overall mFAS |
|---|---|
| Description | Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mFAS included all FAS participants with a positive SARS-CoV-2 RT-qPCR conducted in the central laboratory in NP swab samples at randomization. Analysis based on treatment allocated (as randomized). "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 393 | 406 | 398 | 804 |
| Number (95% Confidence Interval) [Percentage of Participants] |
14.8
82.2%
|
7.9
43.9%
|
12.6
63%
|
10.2
5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0023 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3544 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | To control alpha at a strict 0.05 level, this endpoint was tested hierarchically, with the virologic endpoint tested first. All hierarchical testing was done using the combined dose group. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0212 |
| Comments | P-value was derived CMH test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < = 5 or n(1-p) <= 5 in any treatment group, p-value was based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events |
|---|---|
| Description | Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the observation period. |
| Time Frame | Up to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mFAS included all FAS participants with a positive SARS-CoV-2 RT-qPCR conducted in the central laboratory in NP swab samples at randomization. Analysis based on treatment allocated (as randomized). "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 222 | 224 | 225 | 449 |
| Count of Participants [Participants] |
54
300%
|
45
250%
|
47
235%
|
92
45.1%
|
| Title | Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 |
|---|---|
| Description | Infusion-related reactions are defined as any relevant adverse event that occurs during the infusion or up to day 4. The severity of adverse events (including test findings classified as adverse events) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). |
| Time Frame | Up to Day 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mFAS included all FAS participants with a positive SARS-CoV-2 RT-qPCR conducted in the central laboratory in NP swab samples at randomization. Analysis based on treatment allocated (as randomized). "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 222 | 224 | 225 | 449 |
| Count of Participants [Participants] |
3
16.7%
|
2
11.1%
|
6
30%
|
8
3.9%
|
| Title | Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 |
|---|---|
| Description | Hypersensitivity reactions are defined as any relevant adverse event that occurs during the infusion or up to study day 29. The severity of adverse events (including test findings classified as adverse events) were graded according to NCI-CTCAE. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mFAS included all FAS participants with a positive SARS-CoV-2 RT-qPCR conducted in the central laboratory in NP swab samples at randomization. Analysis based on treatment allocated (as randomized). "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 222 | 224 | 225 | 449 |
| Count of Participants [Participants] |
1
5.6%
|
2
11.1%
|
2
10%
|
4
2%
|
| Title | Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS |
|---|---|
| Description | Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seronegative modified full analysis set (mFAS) was defined as all participants in mFAS with documented seronegative status at the baseline. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 32 | 46 | 41 | 87 |
| Number (80% Confidence Interval) [Cumulative Incidence Percentage] |
23.0
|
15.1
|
20.3
|
17.6
|
| Title | Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS |
|---|---|
| Description | Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 50 | 53 | 58 | 111 |
| Number (80% Confidence Interval) [Cumulative Incidence Percentage] |
20.7
|
18.9
|
11.6
|
15.3
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who went on mechanical ventilation by Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Number (95% Confidence Interval) [Percentage of Participants] |
11.4
63.3%
|
6.1
33.9%
|
8.5
42.5%
|
7.3
3.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0575 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3133 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0849 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who went on mechanical ventilation at Day 29 based on Seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Number (95% Confidence Interval) [Percentage of Participants] |
10.0
55.6%
|
5.8
32.2%
|
7.4
37%
|
6.7
3.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2167 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4123 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2206 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died from Day 6 through Day 29 based on high viral load mFAS were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 222 | 226 | 228 | 454 |
| Number (95% Confidence Interval) [Percentage of Participants] |
13.1
72.8%
|
7.1
39.4%
|
10.1
50.5%
|
8.6
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0383 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3296 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0766 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died from Day 6 through Day 29 Based on seronegative mFAS in pooled analysis phase 3 (cohort 1) and phase 2 (cohort 1A) were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 153 | 167 | 181 | 348 |
| Number (95% Confidence Interval) [Percentage of Participants] |
13.7
76.1%
|
4.8
26.7%
|
7.2
36%
|
6.0
2.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0070 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0507 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0051 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died from Day 1 through Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Number (95% Confidence Interval) [Percentage of participants] |
14.4
80%
|
7.4
41.1%
|
11.0
55%
|
9.2
4.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0174 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2900 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0454 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died from Day 1 through Day 29 based on seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Number (95% Confidence Interval) [Percentage of Participants] |
15.0
83.3%
|
5.2
28.9%
|
8.0
40%
|
6.7
3.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0040 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0413 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0032 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who were discharged by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Number (95% Confidence Interval) [Percentage of Participants] |
80.3
446.1%
|
89.2
495.6%
|
86.9
434.5%
|
88.0
43.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0105 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0622 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0088 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who were discharged by Day 29 based on seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Number (95% Confidence Interval) [Percentage of Participants] |
81.3
451.7%
|
90.1
500.6%
|
89.9
449.5%
|
90.0
44.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0275 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0223 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0072 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died or were readmitted to hospital over time based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)were reported. Readmission to hospital was based on investigator report. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Number (95% Confidence Interval) [Percentage of Participants] |
21.0
116.7%
|
15.2
84.4%
|
17.4
87%
|
16.3
8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1032 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3350 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1314 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died or were readmitted to hospital at Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Readmission to hospital was based on investigator report. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Number (95% Confidence Interval) [Percentage of Participants] |
24.4
135.6%
|
11.6
64.4%
|
12.8
64%
|
12.2
6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00024 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0054 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 181 | 201 | 190 | 391 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
14.9
|
7.7
|
11.7
|
9.7
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A)were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 121 | 148 | 160 | 308 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
15.8
|
5.6
|
8.4
|
7.0
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Number of participants with cumulative incidence of mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 170 | 194 | 183 | 377 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
11.8
|
6.3
|
9.1
|
7.7
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 114 | 143 | 152 | 295 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
10.6
|
6.0
|
7.9
|
7.0
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 170 | 194 | 183 | 377 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
19.1
|
10.2
|
15.0
|
12.7
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 114 | 143 | 152 | 295 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
20.1
|
8.4
|
12.7
|
10.7
|
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on High Viral Load mFAS |
|---|---|
| Description | Time to discharge from hospital based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported. |
| Time Frame | Up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load > 10^6 copies per mL. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 229 | 231 | 236 | 467 |
| Median (95% Confidence Interval) [Days] |
5.0
|
4.0
|
4.0
|
4.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0533 |
| Comments | P-value based on stratified log-rank test with the type of background standard-of-care and baseline serostatus as stratification factors. | |
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0411 |
| Comments | P-value based on stratified log-rank test with the type of background standard-of-care and baseline serostatus as stratification factors. | |
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0229 |
| Comments | P-value based on stratified log-rank test with the type of background standard-of-care and baseline serostatus as stratification factors. | |
| Method | Log Rank | |
| Comments | ||
| Title | Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS |
|---|---|
| Description | Time to discharge from hospital based on Seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported. |
| Time Frame | Up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of matching placebo intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 3 (Cohort 1) and participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 in Phase 2 (Cohort 1A). |
| Measure Participants | 160 | 172 | 188 | 360 |
| Median (95% Confidence Interval) [Days] |
4.5
|
4.0
|
4.0
|
4.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0218 |
| Comments | ||
| Method | Stratified Log Rank Test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0156 |
| Comments | ||
| Method | Stratified Log Rank Test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0067 |
| Comments | ||
| Method | Stratified Log Rank Test | |
| Comments | ||
| Title | Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Treatment-Emergent Serious Adverse Events |
|---|---|
| Description | |
| Time Frame | Up to Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| all FAS participants. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled Placebo | Pooled R10933+R10987 2400 mg IV | Pooled R10933+R10987 8000 mg IV | Pooled Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single dose of R10933+R10987 2400 mg intravenously on Day 1 | Participants received a single dose of R10933+R10987 8000 mg intravenously on Day 1. | Participants received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 730 | 740 | 733 | 1473 |
| Count of Participants [Participants] |
203
1127.8%
|
177
983.3%
|
181
905%
|
358
175.5%
|
| Title | Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 |
|---|---|
| Description | |
| Time Frame | Up to Day 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| all FAS participants. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled Placebo | Pooled R10933+R10987 2400 mg IV | Pooled R10933+R10987 8000 mg IV | Pooled Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single dose of R10933+R10987 2400 mg intravenously on Day 1 | Participants received a single dose of R10933+R10987 8000 mg intravenously on Day 1 | Participants received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 730 | 740 | 733 | 1473 |
| Count of Participants [Participants] |
6
33.3%
|
11
61.1%
|
15
75%
|
26
12.7%
|
| Title | Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 |
|---|---|
| Description | |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| all FAS participants. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported. |
| Arm/Group Title | Pooled Placebo | Pooled R10933+R10987 2400 mg IV | Pooled R10933+R10987 8000 mg IV | Pooled Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single dose of R10933+R10987 2400 mg intravenously on Day 1 | Participants received a single dose of R10933+R10987 8000 mg intravenously on Day 1 | Participants received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 730 | 740 | 733 | 1473 |
| Count of Participants [Participants] |
2
11.1%
|
5
27.8%
|
7
35%
|
12
5.9%
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Number (95% Confidence Interval) [Percentage of Participants] |
17.1
95%
|
8.8
48.9%
|
17.1
85.5%
|
13.0
6.4%
|
4.4
2.1%
|
3.3
1.6%
|
0.0
0%
|
1.5
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2162 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8783 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5583 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7189 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0429 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2103 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died from Day 6 through Day 29 in phase 3 (cohort 1) and phase 2 (cohort 1A) were reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 67 | 79 | 80 | 159 | 86 | 88 | 101 | 189 |
| Number (95% Confidence Interval) [Percentage of Participants] |
19.4
107.8%
|
6.3
35%
|
10.0
50%
|
8.2
4%
|
9.3
4.5%
|
3.4
1.7%
|
5.0
2%
|
4.2
1.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0223 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1256 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0230 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1298 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2642 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0970 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died from Day 1 through Day 29 in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Number (95% Confidence Interval) [Percentage of Participants] |
22.9
127.2%
|
7.5
41.7%
|
11.0
55%
|
9.3
4.6%
|
8.9
4.3%
|
3.3
1.6%
|
5.7
2.3%
|
4.5
1.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0147 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0669 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0094 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1306 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3576 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1476 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who were discharged in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Number (95% Confidence Interval) [Percentage of Participants] |
70.0
388.9%
|
85.0
472.2%
|
84.1
420.5%
|
84.6
41.5%
|
90.0
43.7%
|
94.6
46.1%
|
94.3
38.2%
|
94.4
38.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0481 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0535 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0199 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2784 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2510 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1702 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) by Day 29 were reported. Readmission to hospital was based on investigator report. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Number (95% Confidence Interval) [Percentage of Participants] |
27.1
150.6%
|
13.8
76.7%
|
14.6
73%
|
14.2
7%
|
22.2
10.8%
|
9.8
4.8%
|
11.3
4.6%
|
10.6
4.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0500 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0663 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0229 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0208 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0388 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0092 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death up to Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of death in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) up to Day 29 from randomization were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2: Cohort 1A Combined R10933+R10987 |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 (2400 mg or 8000 mg) intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 51 | 70 | 70 | 140 | 70 | 78 | 90 | 168 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
23.6
|
7.8
|
11.4
|
9.6
|
9.6
|
3.6
|
5.9
|
4.8
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 46 | 66 | 62 | 128 | 68 | 77 | 90 | 167 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
18.2
|
8.9
|
17.6
|
13.4
|
4.7
|
3.5
|
0.0
|
1.7
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | Percentage of participants with cumulative incidence of death or mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 46 | 66 | 62 | 128 | 68 | 77 | 90 | 167 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
30.4
|
12.7
|
21.2
|
17.0
|
11.8
|
4.7
|
5.9
|
5.4
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS |
|---|---|
| Description | Time to discharge from hospital up to Day 56 was reported. |
| Time Frame | Up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 86 | 99 | 198 |
| Median (95% Confidence Interval) [Days] |
8.5
|
5.0
|
6.0
|
6.0
|
4.0
|
3.0
|
3.0
|
3.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0370 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1596 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0444 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1802 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0407 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0523 |
| Comments | ||
| Method | stratified log-rank test | |
| Comments | ||
| Title | Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 11 Based on Seronegative mFAS |
|---|---|
| Description | TWA change from baseline in viral load up to Day 11 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 11, was measured by RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load. |
| Time Frame | Day 1 to Day 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 59 | 76 | 78 | 154 | 80 | 79 | 88 | 167 |
| Least Squares Mean (Standard Error) [log10 copies/mL] |
-1.52
(0.17)
|
-2.03
(0.15)
|
-1.95
(0.15)
|
-2.00
(0.10)
|
-1.28
(0.14)
|
-1.88
(0.14)
|
-2.01
(0.14)
|
-1.95
(0.10)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0245 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0554 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0179 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0035 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 29 |
|---|---|
| Description | TWA change from baseline in viral load up to Day 29 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 29, was measured by quantitative RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 64 | 77 | 79 | 156 | 84 | 82 | 93 | 175 |
| Least Squares Mean (Standard Error) [log10 copies/mL] |
-2.72
(0.22)
|
-3.68
(0.20)
|
-3.69
(0.20)
|
-3.69
(0.14)
|
-2.66
(0.21)
|
-3.31
(0.21)
|
-3.58
(0.20)
|
-3.45
(0.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0250 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0012 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0014 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time |
|---|---|
| Description | Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load. |
| Time Frame | Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. "Number of Participants Analyzed" = participants with measurements at baseline. "Number Analyzed" = participants with measurements for both baseline and the specific study day. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Change at Day 3 |
-1.10
(0.22)
|
-0.90
(0.19)
|
-0.93
(0.19)
|
-0.92
(0.14)
|
-0.85
(0.21)
|
-1.03
(0.20)
|
-1.41
(0.19)
|
-1.23
(0.14)
|
| Change at Day 5 |
-1.97
(0.27)
|
-2.28
(0.23)
|
-1.91
(0.25)
|
-2.11
(0.17)
|
-1.55
(0.25)
|
-2.21
(0.26)
|
-2.24
(0.24)
|
-2.21
(0.18)
|
| Change at Day 7 |
-1.97
(0.30)
|
-2.92
(0.26)
|
-3.22
(0.25)
|
-3.09
(0.18)
|
-2.29
(0.26)
|
-3.06
(0.25)
|
-3.49
(0.24)
|
-3.27
(0.17)
|
| Change at Day 9 |
-2.56
(0.32)
|
-3.89
(0.27)
|
-4.16
(0.27)
|
-4.03
(0.19)
|
-2.90
(0.28)
|
-3.75
(0.26)
|
-3.85
(0.24)
|
-3.80
(0.18)
|
| Change at Day 11 |
-3.22
(0.35)
|
-4.23
(0.29)
|
-4.57
(0.30)
|
-4.41
(0.21)
|
-3.88
(0.32)
|
-4.76
(0.30)
|
-4.34
(0.27)
|
-4.52
(0.2)
|
| Change at Day 13 |
-3.76
(0.35)
|
-5.18
(0.30)
|
-5.00
(0.29)
|
-5.10
(0.21)
|
-4.22
(0.31)
|
-4.56
(0.29)
|
-5.05
(0.27)
|
-4.82
(0.20)
|
| Change at Day 15 |
-4.42
(0.32)
|
-5.41
(0.28)
|
-5.25
(0.27)
|
-5.34
(0.19)
|
-4.14
(0.28)
|
-5.03
(0.27)
|
-5.23
(0.25)
|
-5.14
(0.18)
|
| Change at Day 22 |
-5.29
(0.30)
|
-5.74
(0.24)
|
-5.95
(0.24)
|
-5.85
(0.17)
|
-5.37
(0.30)
|
-5.75
(0.29)
|
-5.77
(0.25)
|
-5.75
(0.19)
|
| Change at Day 29 |
-5.90
(0.24)
|
-6.46
(0.18)
|
-6.60
(0.18)
|
-6.54
(0.13)
|
-5.77
(0.27)
|
-6.34
(0.26)
|
-6.36
(0.23)
|
-6.35
(0.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0623 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0203 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0193 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1206 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0911 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | Difference vs. Placebo by Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0645 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Title | Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Percent Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time |
|---|---|
| Description | Percent change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load. |
| Time Frame | Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The seronegative mFAS was defined as all participants in mFAS with documented seronegative status at the baseline. Number of Participants Analyzed" = participants with measurements at baseline. "Number Analyzed" = participants with measurements for both baseline and the specific study day. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 70 | 80 | 82 | 162 | 90 | 92 | 106 | 198 |
| Percent change at Day 3 |
-92.04
|
-87.52
|
-88.15
|
-87.94
|
-85.92
|
-90.65
|
-96.15
|
-94.15
|
| Percent change at Day 5 |
-98.92
|
-99.48
|
-98.76
|
-99.23
|
-97.18
|
-99.38
|
-99.42
|
-99.39
|
| Percent change at Day 7 |
-98.92
|
-99.88
|
-99.94
|
-99.92
|
-99.49
|
-99.91
|
-99.97
|
-99.95
|
| Percent change at Day 9 |
-99.72
|
-99.99
|
-99.99
|
-99.99
|
-99.87
|
-99.98
|
-99.99
|
-99.98
|
| Percent change at Day 11 |
-99.94
|
-99.99
|
-100.00
|
-100.00
|
-99.99
|
-100.00
|
-100.00
|
-100.00
|
| Percent change at Day 13 |
-99.98
|
-100.00
|
-100.00
|
-100.00
|
-99.99
|
-100.00
|
-100.00
|
-100.00
|
| Percent change at Day 15 |
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-99.99
|
-100.00
|
-100.00
|
-100.00
|
| Percent change at Day 22 |
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
| Percent change at Day 29 |
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
-100.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0623 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0203 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0193 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1206 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0911 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | Percent Difference vs. Placebo at Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0645 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 126 | 129 | 118 | 247 | 103 | 102 | 118 | 220 |
| Number (95% Confidence Interval) [Percentage of Participants] |
17.5
97.2%
|
8.5
47.2%
|
16.9
84.5%
|
12.6
6.2%
|
3.9
1.9%
|
2.9
1.4%
|
0.0
0%
|
1.4
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0481 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9880 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2498 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0457 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2153 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 to Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | Day 6 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 122 | 128 | 115 | 243 | 100 | 98 | 113 | 211 |
| Number (95% Confidence Interval) [Percentage of Participants] |
18.0
100%
|
10.2
56.7%
|
15.7
78.5%
|
12.8
6.3%
|
7.0
3.4%
|
3.1
1.5%
|
4.4
1.8%
|
3.8
1.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0811 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6701 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2006 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3313 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5542 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2214 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 to Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | Day 1 to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 126 | 129 | 118 | 247 | 103 | 102 | 118 | 220 |
| Number (95% Confidence Interval) [Percentage of Participants] |
20.6
114.4%
|
10.9
60.6%
|
16.9
84.5%
|
13.8
6.8%
|
6.8
3.3%
|
2.9
1.4%
|
5.1
2.1%
|
4.1
1.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0389 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5208 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1079 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3315 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5797 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3036 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who were discharged in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported. |
| Time Frame | by Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 126 | 129 | 118 | 247 | 103 | 102 | 118 | 220 |
| Number (95% Confidence Interval) [Percentage of Participants] |
72.2
401.1%
|
83.7
465%
|
78.8
394%
|
81.4
39.9%
|
90.3
43.8%
|
96.1
46.9%
|
94.9
38.4%
|
95.5
38.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0364 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2795 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0588 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0364 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2795 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0588 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS |
|---|---|
| Description | Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) over time were reported. Readmission to hospital was based on investigator report. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 126 | 129 | 118 | 247 | 103 | 102 | 118 | 220 |
| Number (95% Confidence Interval) [Percentage of Participants] |
24.6
136.7%
|
18.6
103.3%
|
22.9
114.5%
|
20.6
10.1%
|
16.5
8%
|
10.8
5.3%
|
11.9
4.8%
|
11.4
4.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (2400mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2635 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): R10933+R10987 (8000mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8013 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Placebo, Pooled (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4160 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2194 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3240 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Phase 2: Cohort 1A (Placebo), Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1981 |
| Comments | P-value is derived Cochran-Mantel-Haenszel (CMH) test stratified by the type of background standard-of-care (antiviral therapies and non-antiviral therapies). If np < =5 or n(1-p) <= 5 in any treatment group, p-value is based on Fisher Exact Test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death Over Time Based on High Viral Load mFAS |
|---|---|
| Description | Cumulative Incidence of Death Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 96 | 110 | 90 | 200 | 85 | 91 | 100 | 191 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
21.1
|
11.2
|
17.9
|
14.3
|
7.2
|
3.1
|
5.3
|
4.3
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation Over Time Based on High Viral Load mFAS |
|---|---|
| Description | Cumulative Incidence of Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 87 | 104 | 83 | 187 | 83 | 90 | 100 | 190 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
18.1
|
8.8
|
18.0
|
13.1
|
4.0
|
3.1
|
0.0
|
1.5
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation Over Time Based on High Viral Load mFAS |
|---|---|
| Description | Cumulative Incidence of Death or Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 87 | 104 | 83 | 187 | 83 | 90 | 100 | 190 |
| Number (95% Confidence Interval) [Cumulative Incidence Percentage] |
27.2
|
15.0
|
24.4
|
19.5
|
9.1
|
4.1
|
5.3
|
4.8
|
| Title | Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS |
|---|---|
| Description | Time to Discharge in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. |
| Time Frame | Up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]. |
| Arm/Group Title | Phase 3: Cohort 1 (Placebo) | Phase 3 (Cohort 1): R10933+R10987 (2400 mg IV) | Phase 3 (Cohort 1): R10933+R10987 (8000 mg IV) | Phase 3 (Cohort 1): Combined R10933+R10987 IV | Phase 2: Cohort 1A (Placebo) | Phase 2 (Cohort 1A): R10933+R10987 (2400 mg IV) | Phase 2 (Cohort 1A): R10933+R10987 (8000 mg IV) | Phase 2 (Cohort 1A): Combined R10933+R10987 IV |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1. | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Cohort 1A. | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg or 8000 mg intravenously on Day 1 in Cohort 1A. |
| Measure Participants | 126 | 129 | 118 | 247 | 103 | 102 | 118 | 220 |
| Median (95% Confidence Interval) [days] |
7.0
|
7.0
|
7.0
|
7.0
|
4.0
|
3.0
|
3.0
|
3.0
|
| Title | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Over Time Based on Seronegative mFAS |
|---|---|
| Description | Time-weighted average daily change over time up to Day 29 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples. |
| Time Frame | Up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seronegative modified full analysis set (mFAS) = all participants in mFAS with documented seroneg status at baseline. "Number of Participants Analyzed" = participants with measurements at baseline. "Number Analyzed" = participants with measurements at both baseline and specific study day. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected/reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 Combined IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 68 | 79 | 70 | 149 |
| Time-weighted average change from baseline from Day 1 to Day 3 |
-0.33
(0.11)
|
-0.40
(0.11)
|
-0.60
(0.12)
|
-0.50
(0.08)
|
| Time-weighted average change from baseline from Day 1 to Day 5 |
-0.55
(0.14)
|
-0.86
(0.14)
|
-0.92
(0.14)
|
-0.89
(0.10)
|
| Time-weighted average change from baseline from Day 1 to Day 7 |
-0.70
(0.14)
|
-1.23
(0.14)
|
-1.23
(0.14)
|
-1.23
(0.10)
|
| Time-weighted average change from baseline from Day 1 to Day 9 |
-0.93
(0.16)
|
-1.47
(0.15)
|
-1.58
(0.16)
|
-1.52
(0.11)
|
| Time-weighted average change from baseline from Day 1 to Day 11 |
-1.12
(0.16)
|
-1.72
(0.16)
|
-1.78
(0.17)
|
-1.75
(0.12)
|
| Time-weighted average change from baseline from Day 1 to Day 13 |
-1.33
(0.18)
|
-1.96
(0.17)
|
-1.95
(0.18)
|
-1.96
(0.12)
|
| Time-weighted average change from baseline from Day 1 to Day 15 |
-1.50
(0.19)
|
-2.19
(0.18)
|
-2.16
(0.19)
|
-2.18
(0.13)
|
| Time-weighted average change from baseline from Day 1 to Day 22 |
-1.89
(0.22)
|
-2.62
(0.21)
|
-2.64
(0.22)
|
-2.63
(0.15)
|
| Time-weighted average change from baseline from Day 1 to Day 29 |
-2.35
(0.24)
|
-2.98
(0.23)
|
-2.95
(0.24)
|
-2.97
(0.17)
|
| Title | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Change From Baseline as Measured by RT-qPCR in NP Swabs Over Time Based on Seronegative mFAS |
|---|---|
| Description | Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load. |
| Time Frame | Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seronegative modified full analysis set (mFAS) = all participants in mFAS with documented seroneg status at baseline. "Number of Participants Analyzed" = participants with measurements at baseline. "Number Analyzed" = participants with measurements at both baseline and specific study day. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected/reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 Combined IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg and 8000 mg) intravenously on Day 1 |
| Measure Participants | 68 | 79 | 70 | 149 |
| Time-weighted average change from baseline from Day 1 to Day 3 |
-0.66
(0.22)
|
-0.81
(0.21)
|
-1.08
(0.23)
|
-0.94
(0.16)
|
| Time-weighted average change from baseline from Day 1 to Day 5 |
-1.18
(0.26)
|
-2.08
(0.26)
|
-2.28
(0.27)
|
-2.18
(0.19)
|
| Time-weighted average change from baseline from Day 1 to Day 7 |
-1.62
(0.30)
|
-2.76
(0.27)
|
-2.56
(0.29)
|
-2.67
(0.20)
|
| Time-weighted average change from baseline from Day 1 to Day 9 |
-2.68
(0.34)
|
-3.24
(0.31)
|
-3.16
(0.32)
|
-3.20
(0.22)
|
| Time-weighted average change from baseline from Day 1 to Day 11 |
-3.55
(0.39)
|
-3.74
(0.38)
|
-3.94
(0.37)
|
-3.87
(0.26)
|
| Time-weighted average change from baseline from Day 1 to Day 13 |
-3.04
(0.38)
|
-5.01
(0.35)
|
-4.25
(0.39)
|
-4.68
(0.26)
|
| Time-weighted average change from baseline from Day 1 to Day 15 |
-4.60
(0.39)
|
-4.67
(0.35)
|
-5.01
(0.36)
|
-4.84
(0.25)
|
| Time-weighted average change from baseline from Day 1 to Day 22 |
-5.89
(0.37)
|
-5.21
(0.31)
|
-5.25
(0.32)
|
-5.23
(0.22)
|
| Time-weighted average change from baseline from Day 1 to Day 29 |
-6.01
(0.32)
|
-6.04
(0.27)
|
-6.16
(0.28)
|
-6.10
(0.20)
|
| Title | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on Seronegative mFAS |
|---|---|
| Description | |
| Time Frame | Through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seronegative modified full analysis set (mFAS) was defined as all participants in mFAS with documented seronegative status at the baseline. As prespecified in protocol, pooled analysis of placebo and combined R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of 2400mg or 8000 mg R10933+R10987 intravenously on Day 1 |
| Measure Participants | 52 | 62 | 59 | 121 |
| Number (80% Confidence Interval) [Percentage of Participants] |
26.9
149.4%
|
17.7
98.3%
|
22.0
110%
|
19.8
9.7%
|
| Title | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on High Viral Load mFAS |
|---|---|
| Description | |
| Time Frame | Through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The High Viral Load mFAS was defined as all participants in mFAS with baseline SARS-CoV-2 viral load greater than (>) 10^6 copies per milliliter (mL). Here "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. As prespecified in protocol, separate analysis for placebo and R10933+R10987 IV (2400 mg and 8000 mg combined doses) were collected and reported for Phase 1 [Cohort 1] and Phase 2 [Cohort 1]. |
| Arm/Group Title | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Placebo | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (2400 mg IV) | Pooled (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): R10933+R10987 (8000 mg IV) | Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Combined R10933+R10987 IV |
|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching R10933+R10987 intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (2400 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 (8000 mg) intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of 2400mg or 8000 mg R10933+R10987 intravenously on Day 1 |
| Measure Participants | 78 | 77 | 80 | 157 |
| Number (80% Confidence Interval) [Percentage of Participants] |
23.1
128.3%
|
23.4
130%
|
13.8
69%
|
18.5
9.1%
|
| Title | Phase 1 [Cohort 1]: Area Under the Concentration-Time Curve From Time 0 to 28 Days Post-dose (AUC0-28) |
|---|---|
| Description | |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in Phase 1 (Cohort 1) who received any study drug of casirivimab and imdevimab and who had at least 1 non-missing drug concentration measurement following the first dose of study drug |
| Arm/Group Title | Phase 1 [Cohort 1]: R10983+10987 2400mg IV | Phase 1 [Cohort 1]: R10983+10987 8000mg IV |
|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 |
| Measure Participants | 16 | 20 |
| AUC0-28 of Casirivimab |
3026
(719)
|
9678
(3362)
|
| AUC0-28 of Imdevimab |
2582
(581)
|
8680
(2930)
|
| Title | Concentration at the End of Infusion (Ceoi) |
|---|---|
| Description | |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received any study drug of casirivimab and imdevimab |
| Arm/Group Title | Phase 1 [Cohort 1]: R10983+10987 2400mg IV | Phase 1 [Cohort 1]: R10983+10987 8000mg IV | Phase 2 (Cohort 1A): R10933+R10987 2400mg IV | Phase 2 (Cohort 1A): R10933+R10987 8000mg IV | Phase 2 (Cohort 1): R10933+R10987 2400mg IV | Phase 2 (Cohort 1): R10933+R10987 8000mg IV | Phase 2 (Cohort 2): R10933+R10987 2400mg IV | Phase 2 (Cohort 2): R10933+R10987 8000mg IV | Phase 2 (Cohort 3): R10933+R10987 2400mg IV | Phase 2 (Cohort 3): R10933+R10987 8000mg IV | Phase 3 (Cohort 1): R10933+R10987 2400mg IV | Phase 3 (Cohort 1): R10933+R10987 8000mg IV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 3 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 3 (Cohort 1). |
| Measure Participants | 16 | 20 | 167 | 155 | 181 | 178 | 55 | 50 | 10 | 11 | 214 | 207 |
| Ceoi of Casirivimab |
231
(110)
|
776
(372)
|
272
(124)
|
847
(300)
|
288
(86.8)
|
848
(261)
|
286
(93.5)
|
921
(262)
|
284
(69.3)
|
708
(128)
|
307
(153)
|
908
(338)
|
| Ceoi of Imdevimab |
243
(117)
|
795
(371)
|
283
(127)
|
868
(298)
|
300
(87.3)
|
880
(268)
|
302
(94.0)
|
946
(244)
|
290
(81.7)
|
738
(124)
|
312
(157)
|
945
(351)
|
| Title | Concentration at Day 28 (C28) |
|---|---|
| Description | |
| Time Frame | Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received any study drug of casirivimab and imdevimab and who had at least 1 non-missing drug concentration measurement following the first dose of study drug |
| Arm/Group Title | Phase 1 [Cohort 1]: R10983+10987 2400mg IV | Phase 1 [Cohort 1]: R10983+10987 8000mg IV | Phase 2 (Cohort 1A): R10933+R10987 2400mg IV | Phase 2 (Cohort 1A): R10933+R10987 8000mg IV | Phase 2 (Cohort 1): R10933+R10987 2400mg IV | Phase 2 (Cohort 1): R10933+R10987 8000mg IV | Phase 2 (Cohort 2): R10933+R10987 2400mg IV | Phase 2 (Cohort 2): R10933+R10987 8000mg IV | Phase 2 (Cohort 3): R10933+R10987 2400mg IV | Phase 2 (Cohort 3): R10933+R10987 8000mg IV | Phase 3 (Cohort 1): R10933+R10987 2400mg IV | Phase 3 (Cohort 1): R10933+R10987 8000mg IV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 1 (Cohort 1) | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 3 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 3 (Cohort 1). |
| Measure Participants | 9 | 9 | 91 | 96 | 91 | 93 | 25 | 26 | 3 | 5 | 149 | 146 |
| C28 of Casirivimab |
50.7
(19.5)
|
166
(108)
|
64.8
(35.9)
|
174
(65.1)
|
50.0
(20.4)
|
144
(89.8)
|
26.4
(18.5)
|
79.4
(61.4)
|
9.06
(2.64)
|
67.8
(31.1)
|
49.1
(40.4)
|
140
(66.1)
|
| C28 of Imdevimab |
36.1
(16.1)
|
131
(84.1)
|
54.7
(37.6)
|
150
(62.9)
|
39.8
(18.9)
|
113
(68.8)
|
18.7
(14.7)
|
60.0
(53.9)
|
5.25
(4.12)
|
52.4
(24.7)
|
40.8
(48.3)
|
114
(62.6)
|
| Title | Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 |
|---|---|
| Description | |
| Time Frame | Through Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ADA analysis set includes all treated participants from all phases/cohorts who received any amount of study drug and had at least one non-missing antibody variables result following the first dose of study drug or placebo. |
| Arm/Group Title | Pooled Placebo | Pooled R10933+R10987 2400mg IV | Pooled REGN10933+REGN10987 8000mg IV |
|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single 2400mg intravenous dose of R10933+R10987 | Participants received a single 8000 mg intravenous dose of R10933+R10987 |
| Measure Participants | 503 | 504 | 497 |
| Count of Participants [Participants] |
489
2716.7%
|
471
2616.7%
|
484
2420%
|
| Title | Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 |
|---|---|
| Description | |
| Time Frame | Through Day 169 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ADA analysis set includes all treated participants from all phases/cohorts who received any amount of study drug and had at least one non-missing antibody variables result following the first dose of study drug or placebo. |
| Arm/Group Title | Pooled Placebo | Pooled R10933+R10987 2400mg IV | Pooled REGN10933+REGN10987 8000mg IV |
|---|---|---|---|
| Arm/Group Description | Participants received a single intravenous dose of placebo matching R10933+R10987 | Participants received a single 2400mg dose of R10933+R10987 intravenously on Day 1 | Participants received a single 8000 mg dose of R10933+R10987 intravenously on Day 1 |
| Measure Participants | 503 | 504 | 497 |
| Count of Participants [Participants] |
467
2594.4%
|
444
2466.7%
|
463
2315%
|
| Title | Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10933 |
|---|---|
| Description | |
| Time Frame | Through Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| NAb analysis set includes all Phase 2/3 treated participants who received any study drug, had at least one non-missing antibody result following the first dose of study drug, and either tested negative at all ADA sampling times or tested positive for ADA with at least one non-missing NAb result after first dose of the study drug. |
| Arm/Group Title | Pooled (Phase 2/3) Placebo | Pooled (Phase 2/3) R10933+R10987 2400mg IV | Pooled (Phase 2/3) REGN10933+REGN10987 8000mg IV |
|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single 2400mg intravenous dose of R10933+R10987 | Participants received a single 8000 mg intravenous dose of R10933+R10987 |
| Measure Participants | 503 | 504 | 497 |
| Anti-drug Antibody (ADA) Negative |
489
2716.7%
|
471
2616.7%
|
484
2420%
|
| Neutralizing antibody (NAb) Positive |
1
5.6%
|
1
5.6%
|
1
5%
|
| Title | Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10987 |
|---|---|
| Description | |
| Time Frame | Through Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| NAb analysis set includes all Phase 2/3 treated participants who received any study drug, had at least one non-missing antibody result following the first dose of study drug, and either tested negative at all ADA sampling times or tested positive for ADA with at least one non-missing NAb result after first dose of the study drug. |
| Arm/Group Title | Pooled (Phase 2/3) Placebo | Pooled (Phase 2/3) R10933+R10987 2400mg IV | Pooled (Phase 2/3) REGN10933+REGN10987 8000mg IV |
|---|---|---|---|
| Arm/Group Description | Participants received single dose of placebo matching to R10933+R10987 intravenously on Day 1 | Participants received a single 2400mg intravenous dose of R10933+R10987 | Participants received a single 8000 mg intravenous dose of R10933+R10987 |
| Measure Participants | 503 | 504 | 497 |
| Anti-drug Antibody (ADA) Negative |
467
2594.4%
|
444
2466.7%
|
463
2315%
|
| Neutralizing antibody (NAb) Positive |
9
50%
|
10
55.6%
|
4
20%
|
Adverse Events
| Time Frame | From first dose of study drug to Day 169 | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||||||||||
| Arm/Group Title | Phase 1 Cohort 1: Placebo IV | Phase 1 Cohort 1: R10933+R10987 2400mg IV | Phase 1 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 1A: Placebo IV | Phase 2 Cohort 1A: R10933+R10987 2400mg IV | Phase 2 Cohort 1A: R10933+R10987 8000mg IV | Phase 2 Cohort 1: Placebo IV | Phase 2 Cohort 1: R10933+R10987 2400mg IV | Phase 2 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 2: Placebo IV | Phase 2 Cohort 2: R10933+R10987 2400mg IV | Phase 2 Cohort 2: R10933+R10987 8000mg IV | Phase 2 Cohort 3: Placebo IV | Phase 2 Cohort 3: R10933+R10987 2400mg IV | Phase 2 Cohort 3: R10933+R10987 8000mg IV | Phase 3 Cohort 1: Placebo IV | Phase 3 Cohort 1: R10933+R10987 2400mg IV | Phase 3 Cohort 1: R10933+R10987 8000mg IV | ||||||||||||||||||
| Arm/Group Description | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 milligrams (mg) intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 1 (Cohort 1). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with COVID-19 symptoms but not requiring supplemental oxygen received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1A). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 1). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on high-flow oxygen therapy but not on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 2). | Participants on mechanical ventilation received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants on mechanical ventilation received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 2 (Cohort 3). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of placebo matching to R10933+R10987 intravenously on Day 1 in Phase 3 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 2400 mg intravenously on Day 1 in Phase 3 (Cohort 1). | Participants with O2 saturation > 93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device received single dose of R10933+R10987 8000 mg intravenously on Day 1 in Phase 3 (Cohort 1). | ||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||
| Phase 1 Cohort 1: Placebo IV | Phase 1 Cohort 1: R10933+R10987 2400mg IV | Phase 1 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 1A: Placebo IV | Phase 2 Cohort 1A: R10933+R10987 2400mg IV | Phase 2 Cohort 1A: R10933+R10987 8000mg IV | Phase 2 Cohort 1: Placebo IV | Phase 2 Cohort 1: R10933+R10987 2400mg IV | Phase 2 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 2: Placebo IV | Phase 2 Cohort 2: R10933+R10987 2400mg IV | Phase 2 Cohort 2: R10933+R10987 8000mg IV | Phase 2 Cohort 3: Placebo IV | Phase 2 Cohort 3: R10933+R10987 2400mg IV | Phase 2 Cohort 3: R10933+R10987 8000mg IV | Phase 3 Cohort 1: Placebo IV | Phase 3 Cohort 1: R10933+R10987 2400mg IV | Phase 3 Cohort 1: R10933+R10987 8000mg IV | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/18 (11.1%) | 0/18 (0%) | 1/20 (5%) | 15/198 (7.6%) | 8/202 (4%) | 7/197 (3.6%) | 28/204 (13.7%) | 25/206 (12.1%) | 21/205 (10.2%) | 13/51 (25.5%) | 25/56 (44.6%) | 19/54 (35.2%) | 7/12 (58.3%) | 8/12 (66.7%) | 4/11 (36.4%) | 42/247 (17%) | 24/246 (9.8%) | 37/246 (15%) | ||||||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||||||||||
| Phase 1 Cohort 1: Placebo IV | Phase 1 Cohort 1: R10933+R10987 2400mg IV | Phase 1 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 1A: Placebo IV | Phase 2 Cohort 1A: R10933+R10987 2400mg IV | Phase 2 Cohort 1A: R10933+R10987 8000mg IV | Phase 2 Cohort 1: Placebo IV | Phase 2 Cohort 1: R10933+R10987 2400mg IV | Phase 2 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 2: Placebo IV | Phase 2 Cohort 2: R10933+R10987 2400mg IV | Phase 2 Cohort 2: R10933+R10987 8000mg IV | Phase 2 Cohort 3: Placebo IV | Phase 2 Cohort 3: R10933+R10987 2400mg IV | Phase 2 Cohort 3: R10933+R10987 8000mg IV | Phase 3 Cohort 1: Placebo IV | Phase 3 Cohort 1: R10933+R10987 2400mg IV | Phase 3 Cohort 1: R10933+R10987 8000mg IV | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/18 (16.7%) | 3/18 (16.7%) | 2/20 (10%) | 43/198 (21.7%) | 29/202 (14.4%) | 32/197 (16.2%) | 63/204 (30.9%) | 47/206 (22.8%) | 47/205 (22.9%) | 20/51 (39.2%) | 31/56 (55.4%) | 26/54 (48.1%) | 9/12 (75%) | 11/12 (91.7%) | 5/11 (45.5%) | 65/247 (26.3%) | 56/246 (22.8%) | 69/246 (28%) | ||||||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||
| Anaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 2/247 (0.8%) | 4 | 2/246 (0.8%) | 2 | 0/246 (0%) | 0 |
| Febrile neutropenia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypercoagulation | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Sickle cell anaemia with crisis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Thrombocytopenia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||
| Acute coronary syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Acute left ventricular failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Acute myocardial infarction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 2/246 (0.8%) | 2 |
| Angina pectoris | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Atrial fibrillation | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/198 (0.5%) | 2 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 3/204 (1.5%) | 3 | 1/206 (0.5%) | 1 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Atrial flutter | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Atrial tachycardia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Bradycardia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cardiac arrest | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 1/204 (0.5%) | 1 | 3/206 (1.5%) | 3 | 1/205 (0.5%) | 1 | 2/51 (3.9%) | 3 | 2/56 (3.6%) | 5 | 3/54 (5.6%) | 4 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 1/11 (9.1%) | 1 | 2/247 (0.8%) | 2 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Cardiac failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 0/246 (0%) | 0 | 2/246 (0.8%) | 2 |
| Cardiac failure acute | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Cardiac failure chronic | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Cardiac failure congestive | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 2/246 (0.8%) | 2 |
| Cardio-respiratory arrest | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 3/247 (1.2%) | 4 | 3/246 (1.2%) | 3 | 2/246 (0.8%) | 2 |
| Cardiogenic shock | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Chronic left ventricular failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Myocardial infarction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Myocarditis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Pulseless electrical activity | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 2 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Tachycardia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 2/206 (1%) | 2 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Ventricular tachycardia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||
| Vertigo positional | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||||||||||||||
| Blindness unilateral | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||
| Abdominal distension | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Abdominal pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Abdominal pain upper | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Dysphagia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Haematemesis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Haematochezia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Ileus | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Impaired gastric emptying | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 2 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Intestinal ischaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Intestinal obstruction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Mallory-Weiss syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pancreatitis acute | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Rectal haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Retroperitoneal haematoma | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Retroperitoneal haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Small intestinal obstruction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||||||||||||||
| Asthenia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 2/202 (1%) | 2 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 2/246 (0.8%) | 2 | 0/246 (0%) | 0 |
| Chest pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 2/246 (0.8%) | 4 | 2/246 (0.8%) | 2 |
| Chills | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 2/12 (16.7%) | 2 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Death | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 2/202 (1%) | 2 | 0/197 (0%) | 0 | 3/204 (1.5%) | 3 | 1/206 (0.5%) | 1 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 2/246 (0.8%) | 2 | 0/246 (0%) | 0 |
| Fatigue | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Generalised oedema | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Multiple organ dysfunction syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 1/206 (0.5%) | 1 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 1/54 (1.9%) | 1 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 3/247 (1.2%) | 3 | 1/246 (0.4%) | 1 | 6/246 (2.4%) | 6 |
| Non-cardiac chest pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Sudden cardiac death | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Systemic inflammatory response syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||
| Acute hepatic failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cholelithiasis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hepatic cirrhosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Ischaemic hepatitis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||||||||||||||
| Anaphylactic reaction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypersensitivity | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Lung transplant rejection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||||||||||||||
| COVID-19 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 | 7/198 (3.5%) | 7 | 0/202 (0%) | 0 | 6/197 (3%) | 6 | 6/204 (2.9%) | 6 | 4/206 (1.9%) | 4 | 7/205 (3.4%) | 7 | 4/51 (7.8%) | 4 | 7/56 (12.5%) | 7 | 8/54 (14.8%) | 10 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 2/11 (18.2%) | 2 | 10/247 (4%) | 10 | 5/246 (2%) | 5 | 8/246 (3.3%) | 9 |
| Appendicitis perforated | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Arthritis bacterial | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Aspergillus infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Burkholderia cepacia complex infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| COVID-19 pneumonia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 4/198 (2%) | 4 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 2/206 (1%) | 2 | 1/205 (0.5%) | 1 | 3/51 (5.9%) | 3 | 2/56 (3.6%) | 2 | 3/54 (5.6%) | 3 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 5/247 (2%) | 5 | 3/246 (1.2%) | 3 | 7/246 (2.8%) | 7 |
| Candida infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Candida sepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cellulitis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Cytomegalovirus infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Device related bacteraemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 2 |
| Emphysematous cholecystitis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Encephalitis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Enterococcal infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Escherichia urinary tract infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Fungaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Herpes simplex | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Herpes zoster | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Ophthalmic herpes zoster | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Osteomyelitis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Osteomyelitis fungal | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Perirectal abscess | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumococcal infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Pneumonia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 5/204 (2.5%) | 5 | 0/206 (0%) | 0 | 3/205 (1.5%) | 3 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 0/246 (0%) | 0 | 3/246 (1.2%) | 4 |
| Pneumonia bacterial | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 3/204 (1.5%) | 3 | 4/206 (1.9%) | 4 | 2/205 (1%) | 2 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumonia klebsiella | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumonia serratia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumonia staphylococcal | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Post procedural infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pseudomonal sepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pulmonary sepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 3/247 (1.2%) | 3 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pyelonephritis acute | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Scrotal abscess | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Sepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 4/204 (2%) | 4 | 1/206 (0.5%) | 1 | 3/205 (1.5%) | 3 | 1/51 (2%) | 1 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Septic shock | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 3/204 (1.5%) | 3 | 2/206 (1%) | 2 | 1/205 (0.5%) | 1 | 2/51 (3.9%) | 2 | 2/56 (3.6%) | 2 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 6/247 (2.4%) | 7 | 2/246 (0.8%) | 2 | 5/246 (2%) | 6 |
| Serratia infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Staphylococcal bacteraemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Staphylococcal infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 2/51 (3.9%) | 2 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Staphylococcal sepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Superinfection bacterial | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Urinary tract candidiasis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Urinary tract infection | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 2/197 (1%) | 2 | 2/204 (1%) | 2 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Urinary tract infection enterococcal | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Urosepsis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Viral cardiomyopathy | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Viral myocarditis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||
| Acetabulum fracture | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Brain herniation | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Endotracheal intubation complication | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Fall | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 2/202 (1%) | 2 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 2/246 (0.8%) | 2 |
| Gastrointestinal stoma complication | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Head injury | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Pancreatic leak | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Post procedural complication | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Post procedural haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Rib fracture | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Stomal hernia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Subdural haematoma | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Toxicity to various agents | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||||||||||||||
| Blood glucose increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| ECG signs of myocardial ischaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Fibrin D dimer increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 2 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Haemoglobin decreased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Hepatic enzyme increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Inflammatory marker increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| International normalised ratio increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Klebsiella test positive | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Mean arterial pressure increased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Oxygen saturation decreased | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 2 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||
| Acidosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Calciphylaxis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Decreased appetite | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Dehydration | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Failure to thrive | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hyperglycaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hyperkalaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypernatraemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypervolaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypoglycaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Hypokalaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypophosphataemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Metabolic acidosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Type 2 diabetes mellitus | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||
| Arthralgia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Compartment syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Muscular weakness | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Myalgia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Neck pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||
| Appendix cancer | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Chronic myelomonocytic leukaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Colon cancer | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||
| Cerebral haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cerebral infarction | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Cerebrovascular accident | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Dementia Alzheimer's type | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Depressed level of consciousness | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Dizziness | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Encephalopathy | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 2/206 (1%) | 2 | 2/205 (1%) | 2 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Haemorrhage intracranial | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Hydrocephalus | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Hypoaesthesia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Ischaemic stroke | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Metabolic encephalopathy | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 2/246 (0.8%) | 2 | 0/246 (0%) | 0 |
| Multiple sclerosis relapse | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Seizure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Syncope | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 3/204 (1.5%) | 3 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Toxic encephalopathy | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Transverse sinus thrombosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Unresponsive to stimuli | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Product Issues | ||||||||||||||||||||||||||||||||||||
| Device occlusion | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||
| Anxiety | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Confusional state | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Delirium | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Mental status changes | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 0/202 (0%) | 0 | 2/197 (1%) | 2 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 3/246 (1.2%) | 3 | 0/246 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||
| Acute kidney injury | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 1/198 (0.5%) | 1 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 2/206 (1%) | 2 | 3/205 (1.5%) | 3 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 4/54 (7.4%) | 4 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 4/247 (1.6%) | 4 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| End stage renal disease | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Haematuria | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Renal failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Renal impairment | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Renal tubular injury | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Ureterolithiasis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||
| Dyspnoea | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 2/198 (1%) | 2 | 0/202 (0%) | 0 | 3/197 (1.5%) | 3 | 2/204 (1%) | 2 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 3/246 (1.2%) | 3 | 3/246 (1.2%) | 4 |
| Hypoxia | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 3/198 (1.5%) | 3 | 1/202 (0.5%) | 1 | 1/197 (0.5%) | 1 | 7/204 (3.4%) | 9 | 3/206 (1.5%) | 3 | 7/205 (3.4%) | 7 | 1/51 (2%) | 1 | 1/56 (1.8%) | 1 | 2/54 (3.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 8/247 (3.2%) | 9 | 8/246 (3.3%) | 8 | 5/246 (2%) | 6 |
| Pneumonitis | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Acute respiratory distress syndrome | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 1/206 (0.5%) | 1 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 4/56 (7.1%) | 4 | 2/54 (3.7%) | 2 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 3/246 (1.2%) | 3 | 2/246 (0.8%) | 2 |
| Acute respiratory failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 5/198 (2.5%) | 5 | 2/202 (1%) | 2 | 2/197 (1%) | 2 | 6/204 (2.9%) | 6 | 10/206 (4.9%) | 10 | 5/205 (2.4%) | 5 | 0/51 (0%) | 0 | 7/56 (12.5%) | 7 | 3/54 (5.6%) | 3 | 2/12 (16.7%) | 2 | 1/12 (8.3%) | 1 | 1/11 (9.1%) | 1 | 11/247 (4.5%) | 12 | 6/246 (2.4%) | 6 | 5/246 (2%) | 6 |
| Alveolar lung disease | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 2 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Aspiration | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Asthma | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Atelectasis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Chronic obstructive pulmonary disease | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 2/246 (0.8%) | 3 |
| Dyspnoea exertional | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Haemoptysis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Idiopathic pulmonary fibrosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Laryngeal stenosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Organising pneumonia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pleural effusion | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pleuritic pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumomediastinum | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumonia aspiration | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pneumothorax | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 2/56 (3.6%) | 2 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Pneumothorax spontaneous | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 2 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pulmonary artery thrombosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pulmonary embolism | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 2/202 (1%) | 2 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 5/206 (2.4%) | 5 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 2/247 (0.8%) | 2 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Pulmonary oedema | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Respiratory arrest | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Respiratory distress | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 1/56 (1.8%) | 1 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Respiratory failure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 2/202 (1%) | 3 | 0/197 (0%) | 0 | 9/204 (4.4%) | 10 | 4/206 (1.9%) | 4 | 6/205 (2.9%) | 8 | 5/51 (9.8%) | 6 | 4/56 (7.1%) | 4 | 5/54 (9.3%) | 6 | 1/12 (8.3%) | 1 | 3/12 (25%) | 3 | 0/11 (0%) | 0 | 7/247 (2.8%) | 8 | 7/246 (2.8%) | 7 | 5/246 (2%) | 5 |
| Tachypnoea | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||
| Decubitus ulcer | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Pruritus | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Subcutaneous emphysema | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 1/56 (1.8%) | 1 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||||||||||||||||||||||||||
| Ileostomy closure | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||||||||||
| Arteriosclerosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Deep vein thrombosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Distributive shock | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Embolism venous | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Haematoma | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Haemorrhage | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypertensive urgency | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 1/197 (0.5%) | 1 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Hypotension | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 2/204 (1%) | 2 | 2/206 (1%) | 2 | 2/205 (1%) | 2 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Hypovolaemic shock | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Orthostatic hypotension | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 1/246 (0.4%) | 1 | 0/246 (0%) | 0 |
| Peripheral artery occlusion | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 1/205 (0.5%) | 1 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Shock | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 1/198 (0.5%) | 1 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 1/51 (2%) | 1 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Shock haemorrhagic | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 1/202 (0.5%) | 1 | 0/197 (0%) | 0 | 1/204 (0.5%) | 1 | 1/206 (0.5%) | 1 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Venous thrombosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 1/247 (0.4%) | 1 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Venous thrombosis limb | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||
| Phase 1 Cohort 1: Placebo IV | Phase 1 Cohort 1: R10933+R10987 2400mg IV | Phase 1 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 1A: Placebo IV | Phase 2 Cohort 1A: R10933+R10987 2400mg IV | Phase 2 Cohort 1A: R10933+R10987 8000mg IV | Phase 2 Cohort 1: Placebo IV | Phase 2 Cohort 1: R10933+R10987 2400mg IV | Phase 2 Cohort 1: R10933+R10987 8000mg IV | Phase 2 Cohort 2: Placebo IV | Phase 2 Cohort 2: R10933+R10987 2400mg IV | Phase 2 Cohort 2: R10933+R10987 8000mg IV | Phase 2 Cohort 3: Placebo IV | Phase 2 Cohort 3: R10933+R10987 2400mg IV | Phase 2 Cohort 3: R10933+R10987 8000mg IV | Phase 3 Cohort 1: Placebo IV | Phase 3 Cohort 1: R10933+R10987 2400mg IV | Phase 3 Cohort 1: R10933+R10987 8000mg IV | |||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/18 (0%) | 1/20 (5%) | 0/198 (0%) | 0/202 (0%) | 0/197 (0%) | 0/204 (0%) | 0/206 (0%) | 0/205 (0%) | 0/51 (0%) | 0/56 (0%) | 0/54 (0%) | 0/12 (0%) | 1/12 (8.3%) | 1/11 (9.1%) | 0/247 (0%) | 1/246 (0.4%) | 2/246 (0.8%) | ||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||
| COVID-19 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Enterocolitis infectious | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Urinary tract infection | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 1/246 (0.4%) | 1 | 1/246 (0.4%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||
| Hyperglycaemia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||
| Peroneal nerve palsy | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/11 (9.1%) | 1 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||
| Delirium | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 1/246 (0.4%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||
| Drug eruption | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||||||||||||||
| Haematoma | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/20 (0%) | 0 | 0/198 (0%) | 0 | 0/202 (0%) | 0 | 0/197 (0%) | 0 | 0/204 (0%) | 0 | 0/206 (0%) | 0 | 0/205 (0%) | 0 | 0/51 (0%) | 0 | 0/56 (0%) | 0 | 0/54 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 0/11 (0%) | 0 | 0/247 (0%) | 0 | 0/246 (0%) | 0 | 0/246 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Clinical Trial Management |
|---|---|
| Organization | Regeneron Pharmaceuticals, Inc |
| Phone | 844-734-6643 |
| clinicaltrials@regeneron.com |
Responsible Party:
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04426695
Other Study ID Numbers:
- R10933-10987-COV-2066
- 2020-002537-15
First Posted:
Jun 11, 2020
Last Update Posted:
Jul 25, 2022
Last Verified:
Jun 1, 2022