Sarilumab COVID-19
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT04327388
Collaborator
Regeneron Pharmaceuticals (Industry)
420
47
3
5.2
8.9
1.7
Study Details
Study Description
Brief Summary
Primary Objective:
To evaluate the clinical efficacy of sarilumab relative to the control arm in adult participants hospitalized with severe or critical Coronavirus Disease 2019 (COVID-19).
Secondary Objectives:
-
Evaluate the 28-day survival rate.
-
Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity.
-
Evaluate changes in the National Early Warning Score 2.
-
Evaluate the duration of predefined symptoms and signs (if applicable).
-
Evaluate the duration of supplemental oxygen dependency (if applicable).
-
Evaluate the incidence of new mechanical ventilation use during the study.
-
Evaluate the duration of new mechanical ventilation use during the Study.
-
Evaluate the proportion of participants requiring rescue medication during the 28-day period.
-
Evaluate need for admission into intensive care unit.
-
Evaluate duration of hospitalization (days).
-
The secondary safety objectives of the study were to evaluate the safety of sarilumab through hospitalization (up to Day 29 if participant was still hospitalized) compared to the control arm as assessed by incidence of:
-
Serious adverse events.
-
Major or opportunistic bacterial or fungal infections in participants with grade 4 neutropenia.
-
Grade greater than or equal to (>=) 2 infusion related reactions.
-
Grade >=2 hypersensitivity reactions.
-
Increase in alanine transaminase (ALT) >=3X upper limit of normal (ULN) (for participants with normal baseline) or greater than 3X ULN AND at least 2-fold increase from baseline value (for participants with abnormal baseline).
-
Major or opportunistic bacterial or fungal infections.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
An individual participant would complete the study approximately 60 days from screening to follow-up on day 60 ±7 days.
Study Design
Study Type:
Interventional
Actual Enrollment
:
420 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19
Actual Study Start Date
:
Mar 28, 2020
Actual Primary Completion Date
:
Jul 31, 2020
Actual Study Completion Date
:
Sep 2, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sarilumab 200 mg Sarilumab 200 milligrams (mg), single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in fraction of inspired oxygen (FiO2) requirement or Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction. |
Drug: Sarilumab SAR153191
Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
Other Names:
|
| Experimental: Sarilumab 400 mg Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
Drug: Sarilumab SAR153191
Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
Other Names:
|
| Placebo Comparator: Placebo Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
Drug: Placebo
Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points [Baseline to Day 29]
Time to improvement of greater than or equal (>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of >=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.
Secondary Outcome Measures
- Percentage of Participants Who Were Alive at Day 29 [Day 29]
Percentage of participants who were alive at Day 29 were reported in this outcome measure.
- Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29 [Baseline, Days 4, 7, 15, 21, and 29]
Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity. Percentage of participants With >=1 point improvement in clinical status from Baseline at Days 4, 7, 15, 21, and 29 (assessed using the 7-point ordinal scale) were reported.
- Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score [Baseline, Days 4, 7, 15, 21, and 29]
Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity.
- Time to Resolution of Fever [Baseline to Day 29]
Resolution of fever was defined as body temperature less than or equal to (<=) 36.6 degree Celsius (°C) (axilla), or <=37.2°C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics/until discharge, whichever was sooner. Time to resolution of fever (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever) - date of first dose + 1. Kaplan-Meier method was used for estimation.
- Time to Resolution of Fever and Improvement in Oxygenation [Baseline to Day 29]
Time to resolution of fever was defined as body temperature <=36.6°C (axilla), or <=37.2 °C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge, whichever was sooner. Improvement in oxygenation was defined as oxygen saturation (SpO2)/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to resolution of fever and improvement in oxygenation (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever and improvement in oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.
- Number of Days With Fever [Baseline to Day 29]
Fever was defined as body temperature greater than (>) 37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period. Number of days with fever were reported. Least square (LS) mean and standard error (SE) were estimated using the analysis of covariance (ANCOVA) model with treatment group and randomization strata as fixed effects.
- Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29 [Baseline, Days 4, 7, 15, 21, and 29]
NEWS2: used to standardize assessment of acute-illness severity, track clinical condition of participants and to alert clinical teams to participant deterioration. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. Percentage of participants in following clinical risk categories were reported: low risk (score 0 to 4); low to medium risk (score of 3 in any individual parameter); medium risk (score 5 to 6); high risk (score 7 to 19).
- Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours [Baseline to Day 29]
Time to NEWS2 <2 and maintained for 24 hours: time (in days) from 1st dose of study drug until 1st occurrence of NEWS score of <2 (maintained for 24 hours); calculated as: date of 1st occurrence/episode of event (NEWS score of <2) - date of 1st dose + 1. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (score of 0 or 1 was allocated) and level of consciousness (score of 0 or 3 was allocated), where 0=normal health condition to 3=worst health condition; higher score=more severity. All scores were summed to get an aggregate score which ranged from 0 to 19, with higher scores=more severity/higher risk. Kaplan-Meier method was used for analysis.
- Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2 [Baseline, Days 4, 7, 15, 21, and 29]
The NEWS2 was used to standardize the assessment of acute-illness severity, track the clinical condition of participants, and to alert clinical teams to participant deterioration. NEWS2 score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. LS means and SE were estimated using ANCOVA model with treatment group and randomization strata as fixed effects, and baseline NEWS2 score as a covariate.
- Time-to-improvement in Oxygenation [Baseline to Day 29]
Time-to-improvement in oxygenation was defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to improvement in oxygenation was calculated as: date of first occurrence/episode of the event (oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.
- Percentage of Participants Alive Off Supplemental Oxygen at Day 29 [Day 29]
Supplemental oxygen was defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
- Percentage of Days With Hypoxemia [Baseline to Day 29]
Hypoxemia (low level of oxygen in the blood) was defined as SpO2 <93% on room air, or required supplemental oxygen, or mechanical ventilatory support. Days meeting the criteria for hypoxemia since the first study dose were counted and the percentage of days with hypoxemia were calculated as:100*number of days with the hypoxemia divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
- Percentage of Days With Supplemental Oxygen Use [Baseline to Day 29]
Supplemental oxygen (oxygen therapy) was defined as oxygen administration using oxygen delivery device (e.g. nasal cannula, simple face mask, non-rebreather mask, high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, extracorporeal life support, etc.). Days meeting the criteria for supplemental oxygen use since the first study dose were counted and the percentage of days with supplemental oxygen use were calculated as:100*number of days with the supplemental oxygen use divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29) . LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
- Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute [Baseline to Day 29]
Resting respiratory rate was measured in terms of number of breaths per minute (bpm) while a person is at rest. Only the days with respiratory rate >24 breath per minute since the first dose were counted and percentage of days with respiratory rate > 24 bpm were calculated as:100*number of days with respiratory rate >24 bpm divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
- Time to Oxygen Saturation >= 94% on Room Air [Baseline to Day 29]
Time to oxygen saturation >=94% on room air was defined as the time (in days) from first dose of study drug until the time of first occurrence of oxygen saturation >=94% and it was calculated as: Date of first occurrence/episode of the event (oxygen saturation >=94%) - date of first dose + 1.Kaplan-Meier method was used for estimation.
- Mean Number of Ventilator Free Days [Baseline to Day 29]
Mean number of ventilator free days in participants were reported.
- Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula [Baseline to Day 29]
Percentage of participants With initiation of mechanical ventilation or non-invasive ventilation, or use of high flow nasal cannula were reported in this outcome measure.
- Percentage of Participants Who Required Rescue Medication [Baseline to Day 28]
Rescue medications were defined as the immunosuppressive (methylprednisolone, dexamethasone and prednisone) therapies. During the course of the study, participant who required rescue therapy was based on the judgement of the study physician.
- Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study [Baseline to Day 29]
Percentage of participants who needed ICU care until Day 29 were reported for those not in an ICU at baseline.
- Number of Days of Hospitalization Among Survivors (Alive Participants) [At Day 60]
Number of days of hospitalization among alive participants were counted at Day 60 since the first dose. LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
- Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [Baseline up to 60 days]
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Treatment-emergent AEs (TEAEs) were the AEs that developed or worsened or became serious during the TEAE period (from the time of first dose of study drug to the last dose of study drug + 60 days). SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event.
- Number of Participants With Major or Opportunistic Bacterial or Fungal Infections [Baseline up to 60 days]
Major or opportunistic bacterial or fungal infections was considered as an adverse event of special interest (AESI: defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).
- Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection [Baseline up to 60 days]
Grade 4 neutropenia was defined as participants with absolute neutrophil count (ANC) <500 per cubic millimeter (mm^3). Grade 4 neutropenia with concurrent invasive infection was defined as infections and infestations (in participants with Grade 4 neutropenia) within 1 week of ANC <500/mm^3 and was considered as an AESI (defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).
- Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation [Baseline up to 60 days]
Grade >=2 (moderate) infusion related reactions (defined as any TEAE signs or symptoms experienced by participants who received study medication within 24 hours of the start of infusion) and Grade >=2 (moderate) hypersensitivity reactions (anaphylactic reaction, hypersensitivity or angioedema and moderate reactions) were considered as AESI which was defined as an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Gastrointestinal Perforation was defined as formation of a hole through the stomach, large bowel or small intestine.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets [Baseline up to 60 days]
Criteria for PCSA: Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (male) and <=95 g/L (female); greater than or equal to (>=) 185 g/L (male) and >=165 g/L (female); and decrease from baseline >=20 g/L. Leukocytes: <3.0*10^9/Liters (L) (Non-Black) or <2.0*10^9/L (black); >=16.0*10^9/L. Platelets: < 100*10^9/L; >=700*10^9/L.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters [Baseline up to 60 days]
Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline; >= 100% change from baseline.
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters [Baseline up to 60 days]
Alanine Aminotransferase (ALT): >3 upper limit of normal (ULN); >5 ULN; >10 ULN and >20 ULN. Bilirubin: >1.5 ULN; >2 ULN.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria :
Participants must be >=18 years of age. Participants must be hospitalized for less than or equal to 7 days with evidence of pneumonia and have one of the following disease categories: severe disease or critical disease.
Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.
Exclusion criteria:
Unlikely to survive after 48 hours from screening or unlikely to remain at the investigational site beyond 48 hours. Participants with multi organ dysfunction or requiring extracorporeal life support or renal replacement therapy were excluded.
Presence of neutropenia less than 2000/cubic millimeter (mmˆ3), aspartate transaminase or ALT greater than 5X ULN, platelets less than 50,000/mmˆ3.
Prior immunosuppressive therapies. Use of systemic chronic corticosteroids for non-COVID-19 related condition. Known or suspected history of tuberculosis. Suspected or known active systemic bacterial or fungal infections.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 0320001 | Caba | Argentina | 1430 | |
| 2 | Investigational Site Number 0320003 | Caba | Argentina | C1180AAX | |
| 3 | Investigational Site Number 0320004 | Caba | Argentina | C1426AAM | |
| 4 | Investigational Site Number 0760003 | Porto Alegre | Brazil | 90110-270 | |
| 5 | Investigational Site Number 0760001 | Sao Paulo | Brazil | 01327-001 | |
| 6 | Investigational Site Number 0760002 | Sao Paulo | Brazil | 04231-030 | |
| 7 | Investigational Site Number 0760004 | São José Do Rio Preto | Brazil | 15090-000 | |
| 8 | Investigational Site Number 0760005 | São Paulo | Brazil | 04321-120 | |
| 9 | Investigational Site Number 1240001 | Montreal | Canada | H2X3E4 | |
| 10 | Investigational Site Number 1240005 | Montreal | Canada | H4A 3J1 | |
| 11 | Investigational Site Number 1240004 | Toronto | Canada | M4N3M5 | |
| 12 | Investigational Site Number 1240002 | Toronto | Canada | M5G 2N2 | |
| 13 | Investigational Site Number 1240003 | Vancouver | Canada | V5Z 1M9 | |
| 14 | Investigational Site Number 1520003 | Santiago | Chile | 750-0691 | |
| 15 | Investigational Site Number 1520002 | Santiago | Chile | 80004005 | |
| 16 | Investigational Site Number 1520004 | Santiago | Chile | ||
| 17 | Investigational Site Number 1520001 | Talca | Chile | 3460001 | |
| 18 | Investigational Site Number 2500001 | Bordeaux Cedex | France | 33076 | |
| 19 | Investigational Site Number 2500007 | Clamart | France | 92140 | |
| 20 | Investigational Site Number 2500006 | La Roche Sur Yon Cedex 9 | France | 85925 | |
| 21 | Investigational Site Number 2500002 | Nantes | France | 44093 | |
| 22 | Investigational Site Number 2500005 | Paris Cedex 18 | France | 75877 | |
| 23 | Investigational Site Number 2500003 | Strasbourg | France | 67098 | |
| 24 | Investigational Site Number 2500004 | Suresnes | France | 92151 | |
| 25 | Investigational Site Number 2760002 | Essen | Germany | 45147 | |
| 26 | Investigational Site Number 2760004 | Köln | Germany | 50937 | |
| 27 | Investigational Site Number 2760001 | Münster | Germany | 48149 | |
| 28 | Investigational site number 3760003 | Ashdod | Israel | 7747629 | |
| 29 | Investigational Site Number 3760002 | Jerusalem | Israel | 91120 | |
| 30 | Investigational Site Number 3760001 | Ramat Gan | Israel | 52662 | |
| 31 | Investigational Site Number 3800005 | Milano | Italy | 20122 | |
| 32 | Investigational Site Number 3800001 | Milano | Italy | 20132 | |
| 33 | Investigational Site Number 3800002 | Milano | Italy | 20157 | |
| 34 | Investigational Site Number 3800003 | Modena | Italy | 41100 | |
| 35 | Investigational Site Number 3800004 | Parma | Italy | 43100 | |
| 36 | Investigational Site Number 3800006 | Rozzano | Italy | 20089 | |
| 37 | Investigational Site Number 3920002 | Fuchu-Shi | Japan | ||
| 38 | Investigational Site Number 3920003 | Iruma-Gun | Japan | ||
| 39 | Investigational Site Number 3920001 | Kamakura-Shi | Japan | ||
| 40 | Investigational Site Number 6430003 | Moscow | Russian Federation | 111539 | |
| 41 | Investigational Site Number 6430002 | Moscow | Russian Federation | 123182 | |
| 42 | Investigational Site Number 6430001 | Moscow | Russian Federation | 129301 | |
| 43 | Investigational Site Number 7240003 | Barcelona | Spain | 08035 | |
| 44 | Investigational Site Number 7240004 | Barcelona | Spain | 08036 | |
| 45 | Investigational Site Number 7240002 | Madrid | Spain | 28007 | |
| 46 | Investigational Site Number 7240005 | Madrid | Spain | 28034 | |
| 47 | Investigational Site Number 7240001 | Madrid | Spain | 28046 |
Sponsors and Collaborators
- Sanofi
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT04327388
Other Study ID Numbers:
- EFC16844
- 2020-001162-12
- U1111-1249-6021
First Posted:
Mar 31, 2020
Last Update Posted:
Mar 17, 2022
Last Verified:
Mar 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
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study was conducted at 46 active centers in 11 countries. A total of 431 participants were screened between 28 March 2020 and 02 July 2020, of which 10 participants were screen failures and 1 participant was randomized twice and thus excluded. Therefore, a total of 420 participants were randomized in the study treatment by the interactive response technology (IRT) (2:2:1 ratio) to receive sarilumab 200 milligrams (mg)/400 mg and placebo. Screen failures were mainly due to exclusion criteria met. |
|---|---|
| Pre-assignment Detail | Randomization was stratified by severity of illness (severe disease, critical disease) and use of systemic corticosteroids (Yes/No). |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in fraction of inspired oxygen (FiO2) requirement or Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Period Title: Overall Study | |||
| STARTED | 161 | 173 | 86 |
| Treated | 159 | 173 | 84 |
| Participants Who Received Second Dose | 13 | 11 | 5 |
| COMPLETED | 141 | 153 | 75 |
| NOT COMPLETED | 20 | 20 | 11 |
Baseline Characteristics
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Total of all reporting groups |
| Overall Participants | 161 | 173 | 86 | 420 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
58.3
(13.7)
|
58.0
(14.1)
|
59.9
(14.8)
|
58.5
(14.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
52
32.3%
|
74
42.8%
|
30
34.9%
|
156
37.1%
|
| Male |
109
67.7%
|
99
57.2%
|
56
65.1%
|
264
62.9%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
2
1.2%
|
2
1.2%
|
1
1.2%
|
5
1.2%
|
| Asian |
5
3.1%
|
9
5.2%
|
6
7%
|
20
4.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
1.2%
|
1
0.2%
|
| Black or African American |
3
1.9%
|
5
2.9%
|
1
1.2%
|
9
2.1%
|
| White |
128
79.5%
|
128
74%
|
69
80.2%
|
325
77.4%
|
| More than one race |
0
0%
|
3
1.7%
|
0
0%
|
3
0.7%
|
| Unknown or Not Reported |
23
14.3%
|
26
15%
|
8
9.3%
|
57
13.6%
|
| Clinical Status: 7-point ordinal scale (Count of Participants) | ||||
| Scale Score 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Scale Score 2 |
17
10.6%
|
24
13.9%
|
10
11.6%
|
51
12.1%
|
| Scale Score 3 |
28
17.4%
|
21
12.1%
|
11
12.8%
|
60
14.3%
|
| Scale Score 4 |
113
70.2%
|
128
74%
|
65
75.6%
|
306
72.9%
|
| Scale Score 5 |
3
1.9%
|
0
0%
|
0
0%
|
3
0.7%
|
| Scale Score 6 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Scale Score 7 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points |
|---|---|
| Description | Time to improvement of greater than or equal (>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of >=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on modified intention-to-treat (mITT) population which included all participants who were treated with study medication and were analyzed according to the initial treatment assigned to the participant (as randomized). |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
10.0
|
10.0
|
12.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sarilumab 200 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9561 |
| Comments | ||
| Method | Log-rank test | |
| Comments | Analyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.026 | |
| Confidence Interval |
(2-Sided) 95% 0.751 to 1.402 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio for estimation of treatment effect of each sarilumab dose versus placebo was assessed by cox proportional hazard model stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sarilumab 400 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3376 |
| Comments | ||
| Method | Log-rank test | |
| Comments | Analyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.135 | |
| Confidence Interval |
(2-Sided) 95% 0.835 to 1.543 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Hazard ratio for estimation of treatment effect of each sarilumab dose versus placebo was assessed by cox proportional hazard model stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
| Title | Percentage of Participants Who Were Alive at Day 29 |
|---|---|
| Description | Percentage of participants who were alive at Day 29 were reported in this outcome measure. |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Number [percentage of participants] |
89.9
55.8%
|
91.9
53.1%
|
91.7
106.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sarilumab 200 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6280 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | By Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -9.27 to 5.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sarilumab 400 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8478 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | By Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT. | |
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -6.93 to 7.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29 |
|---|---|
| Description | Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity. Percentage of participants With >=1 point improvement in clinical status from Baseline at Days 4, 7, 15, 21, and 29 (assessed using the 7-point ordinal scale) were reported. |
| Time Frame | Baseline, Days 4, 7, 15, 21, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Day 4 |
25.2
15.7%
|
25.4
14.7%
|
23.8
27.7%
|
| Day 7 |
51.6
32%
|
48.6
28.1%
|
42.9
49.9%
|
| Day 15 |
74.8
46.5%
|
76.9
44.5%
|
71.4
83%
|
| Day 21 |
80.5
50%
|
81.5
47.1%
|
85.7
99.7%
|
| Day 29 |
84.9
52.7%
|
84.4
48.8%
|
88.1
102.4%
|
| Title | Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score |
|---|---|
| Description | Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity. |
| Time Frame | Baseline, Days 4, 7, 15, 21, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Day 4 |
0.1
(0.9)
|
0.1
(1.0)
|
0.2
(0.9)
|
| Day 7 |
0.7
(1.5)
|
0.7
(1.6)
|
0.7
(1.4)
|
| Day 15 |
1.9
(1.8)
|
2.0
(1.9)
|
1.7
(1.8)
|
| Day 21 |
2.3
(1.9)
|
2.3
(1.9)
|
2.5
(1.7)
|
| Day 29 |
2.5
(1.9)
|
2.5
(1.9)
|
2.7
(1.6)
|
| Title | Time to Resolution of Fever |
|---|---|
| Description | Resolution of fever was defined as body temperature less than or equal to (<=) 36.6 degree Celsius (°C) (axilla), or <=37.2°C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics/until discharge, whichever was sooner. Time to resolution of fever (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever) - date of first dose + 1. Kaplan-Meier method was used for estimation. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
8.0
|
9.0
|
7.0
|
| Title | Time to Resolution of Fever and Improvement in Oxygenation |
|---|---|
| Description | Time to resolution of fever was defined as body temperature <=36.6°C (axilla), or <=37.2 °C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge, whichever was sooner. Improvement in oxygenation was defined as oxygen saturation (SpO2)/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to resolution of fever and improvement in oxygenation (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever and improvement in oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
9.0
|
10.0
|
8.0
|
| Title | Number of Days With Fever |
|---|---|
| Description | Fever was defined as body temperature greater than (>) 37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period. Number of days with fever were reported. Least square (LS) mean and standard error (SE) were estimated using the analysis of covariance (ANCOVA) model with treatment group and randomization strata as fixed effects. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 143 | 159 | 77 |
| Least Squares Mean (Standard Error) [days] |
1.2
(0.23)
|
1.3
(0.21)
|
1.8
(0.30)
|
| Title | Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29 |
|---|---|
| Description | NEWS2: used to standardize assessment of acute-illness severity, track clinical condition of participants and to alert clinical teams to participant deterioration. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. Percentage of participants in following clinical risk categories were reported: low risk (score 0 to 4); low to medium risk (score of 3 in any individual parameter); medium risk (score 5 to 6); high risk (score 7 to 19). |
| Time Frame | Baseline, Days 4, 7, 15, 21, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 169 | 84 |
| Baseline: Low |
28.8
17.9%
|
22.1
12.8%
|
34.2
39.8%
|
| Baseline: Low to Medium |
0
0%
|
0
0%
|
0
0%
|
| Baseline: Medium |
34.2
21.2%
|
37.4
21.6%
|
27.8
32.3%
|
| Baseline: High |
37.0
23%
|
40.5
23.4%
|
38.0
44.2%
|
| Day 4: Low |
52.8
32.8%
|
56.2
32.5%
|
40.5
47.1%
|
| Day 4: Low to Medium |
0.6
0.4%
|
1.2
0.7%
|
0
0%
|
| Day 4: Medium |
19.5
12.1%
|
16.6
9.6%
|
28.6
33.3%
|
| Day 4: High |
27.0
16.8%
|
26.0
15%
|
31.0
36%
|
| Day 7: Low |
57.0
35.4%
|
60.8
35.1%
|
51.4
59.8%
|
| Day 7: Low to Medium |
0
0%
|
2.1
1.2%
|
0
0%
|
| Day 7: Medium |
20.0
12.4%
|
10.5
6.1%
|
20.3
23.6%
|
| Day 7: High |
23.0
14.3%
|
26.6
15.4%
|
28.4
33%
|
| Day 15: Low |
52.5
32.6%
|
52.2
30.2%
|
61.1
71%
|
| Day 15: Low to Medium |
0
0%
|
1.5
0.9%
|
2.8
3.3%
|
| Day 15: Medium |
21.3
13.2%
|
19.4
11.2%
|
13.9
16.2%
|
| Day 15: High |
26.2
16.3%
|
26.9
15.5%
|
22.2
25.8%
|
| Day 21: Low |
44.8
27.8%
|
50.0
28.9%
|
66.7
77.6%
|
| Day 21: Low to Medium |
13.8
8.6%
|
0
0%
|
0
0%
|
| Day 21: Medium |
24.1
15%
|
21.1
12.2%
|
8.3
9.7%
|
| Day 21: High |
17.2
10.7%
|
28.9
16.7%
|
25.0
29.1%
|
| Day 29: Low |
57.1
35.5%
|
27.8
16.1%
|
60.0
69.8%
|
| Day 29: Low to Medium |
0
0%
|
0
0%
|
0
0%
|
| Day 29: Medium |
14.3
8.9%
|
27.8
16.1%
|
20.0
23.3%
|
| Day 29: High |
28.6
17.8%
|
44.4
25.7%
|
20.0
23.3%
|
| Title | Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours |
|---|---|
| Description | Time to NEWS2 <2 and maintained for 24 hours: time (in days) from 1st dose of study drug until 1st occurrence of NEWS score of <2 (maintained for 24 hours); calculated as: date of 1st occurrence/episode of event (NEWS score of <2) - date of 1st dose + 1. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (score of 0 or 1 was allocated) and level of consciousness (score of 0 or 3 was allocated), where 0=normal health condition to 3=worst health condition; higher score=more severity. All scores were summed to get an aggregate score which ranged from 0 to 19, with higher scores=more severity/higher risk. Kaplan-Meier method was used for analysis. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
9.0
|
9.0
|
11.0
|
| Title | Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2 |
|---|---|
| Description | The NEWS2 was used to standardize the assessment of acute-illness severity, track the clinical condition of participants, and to alert clinical teams to participant deterioration. NEWS2 score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. LS means and SE were estimated using ANCOVA model with treatment group and randomization strata as fixed effects, and baseline NEWS2 score as a covariate. |
| Time Frame | Baseline, Days 4, 7, 15, 21, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 146 | 159 | 79 |
| Day 4 |
-1.07
(0.212)
|
-1.25
(0.198)
|
-0.36
(0.274)
|
| Day 7 |
-1.63
(0.265)
|
-1.47
(0.245)
|
-0.83
(0.338)
|
| Day 15 |
-2.10
(0.508)
|
-1.83
(0.467)
|
-2.36
(0.641)
|
| Day 21 |
-3.02
(0.769)
|
-2.24
(0.676)
|
-2.96
(1.090)
|
| Day 29 |
-2.57
(0.936)
|
-1.27
(0.884)
|
-3.64
(1.508)
|
| Title | Time-to-improvement in Oxygenation |
|---|---|
| Description | Time-to-improvement in oxygenation was defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to improvement in oxygenation was calculated as: date of first occurrence/episode of the event (oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
6.0
|
6.0
|
7.0
|
| Title | Percentage of Participants Alive Off Supplemental Oxygen at Day 29 |
|---|---|
| Description | Supplemental oxygen was defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device. |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Number [percentage of participants] |
84.9
52.7%
|
83.8
48.4%
|
86.9
101%
|
| Title | Percentage of Days With Hypoxemia |
|---|---|
| Description | Hypoxemia (low level of oxygen in the blood) was defined as SpO2 <93% on room air, or required supplemental oxygen, or mechanical ventilatory support. Days meeting the criteria for hypoxemia since the first study dose were counted and the percentage of days with hypoxemia were calculated as:100*number of days with the hypoxemia divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Least Squares Mean (Standard Error) [percentage of days] |
73.01
(2.063)
|
75.10
(1.941)
|
76.32
(2.724)
|
| Title | Percentage of Days With Supplemental Oxygen Use |
|---|---|
| Description | Supplemental oxygen (oxygen therapy) was defined as oxygen administration using oxygen delivery device (e.g. nasal cannula, simple face mask, non-rebreather mask, high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, extracorporeal life support, etc.). Days meeting the criteria for supplemental oxygen use since the first study dose were counted and the percentage of days with supplemental oxygen use were calculated as:100*number of days with the supplemental oxygen use divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29) . LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Least Squares Mean (Standard Error) [percentage of days] |
70.57
(2.082)
|
73.30
(1.959)
|
73.23
(2.748)
|
| Title | Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute |
|---|---|
| Description | Resting respiratory rate was measured in terms of number of breaths per minute (bpm) while a person is at rest. Only the days with respiratory rate >24 breath per minute since the first dose were counted and percentage of days with respiratory rate > 24 bpm were calculated as:100*number of days with respiratory rate >24 bpm divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Hence, overall number of participants analyzed = participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 150 | 164 | 78 |
| Least Squares Mean (Standard Error) [percentage of days] |
14.74
(1.582)
|
14.58
(1.485)
|
15.74
(2.105)
|
| Title | Time to Oxygen Saturation >= 94% on Room Air |
|---|---|
| Description | Time to oxygen saturation >=94% on room air was defined as the time (in days) from first dose of study drug until the time of first occurrence of oxygen saturation >=94% and it was calculated as: Date of first occurrence/episode of the event (oxygen saturation >=94%) - date of first dose + 1.Kaplan-Meier method was used for estimation. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Median (95% Confidence Interval) [days] |
8.0
|
8.0
|
8.0
|
| Title | Mean Number of Ventilator Free Days |
|---|---|
| Description | Mean number of ventilator free days in participants were reported. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Mean (Standard Deviation) [days] |
23.8
(9.4)
|
24.0
(8.8)
|
24.9
(8.6)
|
| Title | Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula |
|---|---|
| Description | Percentage of participants With initiation of mechanical ventilation or non-invasive ventilation, or use of high flow nasal cannula were reported in this outcome measure. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 127 | 141 | 68 |
| Number [percentage of participants] |
20.5
12.7%
|
23.4
13.5%
|
19.1
22.2%
|
| Title | Percentage of Participants Who Required Rescue Medication |
|---|---|
| Description | Rescue medications were defined as the immunosuppressive (methylprednisolone, dexamethasone and prednisone) therapies. During the course of the study, participant who required rescue therapy was based on the judgement of the study physician. |
| Time Frame | Baseline to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Number [percentage of participants] |
13.8
8.6%
|
15.0
8.7%
|
22.6
26.3%
|
| Title | Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study |
|---|---|
| Description | Percentage of participants who needed ICU care until Day 29 were reported for those not in an ICU at baseline. |
| Time Frame | Baseline to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 98 | 114 | 56 |
| Number [percentage of participants] |
11.2
7%
|
14.9
8.6%
|
12.5
14.5%
|
| Title | Number of Days of Hospitalization Among Survivors (Alive Participants) |
|---|---|
| Description | Number of days of hospitalization among alive participants were counted at Day 60 since the first dose. LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects. |
| Time Frame | At Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 142 | 155 | 75 |
| Least Squares Mean (Standard Error) [days] |
15.6
(0.96)
|
16.1
(0.91)
|
15.9
(1.27)
|
| Title | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) |
|---|---|
| Description | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Treatment-emergent AEs (TEAEs) were the AEs that developed or worsened or became serious during the TEAE period (from the time of first dose of study drug to the last dose of study drug + 60 days). SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population which included all randomized participants who were treated with the study medication and were analyzed according to the actual treatment received. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Count of Participants [Participants] |
42
26.1%
|
51
29.5%
|
20
23.3%
|
| Title | Number of Participants With Major or Opportunistic Bacterial or Fungal Infections |
|---|---|
| Description | Major or opportunistic bacterial or fungal infections was considered as an adverse event of special interest (AESI: defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required). |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Count of Participants [Participants] |
8
5%
|
15
8.7%
|
3
3.5%
|
| Title | Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection |
|---|---|
| Description | Grade 4 neutropenia was defined as participants with absolute neutrophil count (ANC) <500 per cubic millimeter (mm^3). Grade 4 neutropenia with concurrent invasive infection was defined as infections and infestations (in participants with Grade 4 neutropenia) within 1 week of ANC <500/mm^3 and was considered as an AESI (defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required). |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field signifies that no participants had Grade 4 neutropenia and therefore were not evaluable. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Grade 4 neutropenia |
3
1.9%
|
6
3.5%
|
0
0%
|
| Grade 4 neutropenia with concurrent invasive infection |
0
0%
|
0
0%
|
| Title | Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation |
|---|---|
| Description | Grade >=2 (moderate) infusion related reactions (defined as any TEAE signs or symptoms experienced by participants who received study medication within 24 hours of the start of infusion) and Grade >=2 (moderate) hypersensitivity reactions (anaphylactic reaction, hypersensitivity or angioedema and moderate reactions) were considered as AESI which was defined as an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Gastrointestinal Perforation was defined as formation of a hole through the stomach, large bowel or small intestine. |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 159 | 173 | 84 |
| Grade >=2 Infusion related reactions |
1
0.6%
|
6
3.5%
|
0
0%
|
| Grade >=2 Hypersensitivity reactions |
1
0.6%
|
7
4%
|
0
0%
|
| Gastrointestinal perforation |
1
0.6%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets |
|---|---|
| Description | Criteria for PCSA: Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (male) and <=95 g/L (female); greater than or equal to (>=) 185 g/L (male) and >=165 g/L (female); and decrease from baseline >=20 g/L. Leukocytes: <3.0*10^9/Liters (L) (Non-Black) or <2.0*10^9/L (black); >=16.0*10^9/L. Platelets: < 100*10^9/L; >=700*10^9/L. |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 156 | 170 | 84 |
| Hemoglobin <=115 g/L (male) and <=95 g/L (female) |
29
18%
|
34
19.7%
|
15
17.4%
|
| Hemoglobin >=185 g/L (male) and >=165 g/L (female) |
0
0%
|
0
0%
|
0
0%
|
| Hemoglobin decrease from baseline >=20 g/L |
32
19.9%
|
30
17.3%
|
15
17.4%
|
| Leukocytes <3.0*10^9/L (Non-Black) or <2.0*10^9/L (black) |
19
11.8%
|
31
17.9%
|
1
1.2%
|
| Leukocytes >=16*10^9/L |
13
8.1%
|
21
12.1%
|
6
7%
|
| Platelets <100*10^9/L |
2
1.2%
|
7
4%
|
3
3.5%
|
| Platelets >=700*10^9/L |
3
1.9%
|
2
1.2%
|
2
2.3%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters |
|---|---|
| Description | Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline; >= 100% change from baseline. |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 156 | 170 | 84 |
| Creatinine >=150 mcmol/L |
15
9.3%
|
15
8.7%
|
5
5.8%
|
| >=30% change from baseline in Creatinine |
31
19.3%
|
30
17.3%
|
10
11.6%
|
| >=100% change from baseline in Creatinine |
6
3.7%
|
7
4%
|
3
3.5%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters |
|---|---|
| Description | Alanine Aminotransferase (ALT): >3 upper limit of normal (ULN); >5 ULN; >10 ULN and >20 ULN. Bilirubin: >1.5 ULN; >2 ULN. |
| Time Frame | Baseline up to 60 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. |
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. |
| Measure Participants | 156 | 169 | 84 |
| ALT >3 ULN |
60
37.3%
|
63
36.4%
|
24
27.9%
|
| ALT >5 ULN |
28
17.4%
|
25
14.5%
|
12
14%
|
| ALT >10 ULN |
6
3.7%
|
5
2.9%
|
3
3.5%
|
| ALT >20 ULN |
1
0.6%
|
0
0%
|
0
0%
|
| Bilirubin >1.5 ULN |
5
3.1%
|
4
2.3%
|
4
4.7%
|
| Bilirubin >2 ULN |
4
2.5%
|
2
1.2%
|
2
2.3%
|
Adverse Events
| Time Frame | All AEs were collected from the time of first dose of study drug up to 60 days regardless of seriousness or relationship to study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported AEs and deaths were TEAEs that developed/worsened in grade or became serious during 'treatment-emergent adverse event period' (from the time of first dose of study drug to the last dose of study drug + 60 days). Analysis was performed on safety population. | |||||
| Arm/Group Title | Sarilumab 200 mg | Sarilumab 400 mg | Placebo | |||
| Arm/Group Description | Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction. | |||
All Cause Mortality |
||||||
| Sarilumab 200 mg | Sarilumab 400 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/159 (10.7%) | 18/173 (10.4%) | 9/84 (10.7%) | |||
Serious Adverse Events |
||||||
| Sarilumab 200 mg | Sarilumab 400 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/159 (26.4%) | 51/173 (29.5%) | 20/84 (23.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Blood Loss Anaemia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Leukopenia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Neutropenia | 1/159 (0.6%) | 1 | 3/173 (1.7%) | 3 | 0/84 (0%) | 0 |
| Thrombocytopenia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial Fibrillation | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 3/84 (3.6%) | 3 |
| Cardiac Arrest | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Cardio-Respiratory Arrest | 1/159 (0.6%) | 1 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Intracardiac Thrombus | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Pulseless Electrical Activity | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Ventricular Tachycardia | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Eye disorders | ||||||
| Entropion | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Dysphagia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Gastric Ulcer Perforation | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Intra-Abdominal Haematoma | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Megacolon | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| General disorders | ||||||
| Death | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Hyperthermia | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Multiple Organ Dysfunction Syndrome | 2/159 (1.3%) | 2 | 3/173 (1.7%) | 3 | 3/84 (3.6%) | 3 |
| Physical Deconditioning | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Sudden Death | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Hepatic Steatosis | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hepatitis | 1/159 (0.6%) | 1 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hepatitis Acute | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hepatocellular Injury | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Infections and infestations | ||||||
| Abscess Limb | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Bacterial Infection | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 2/84 (2.4%) | 2 |
| Covid-19 Pneumonia | 11/159 (6.9%) | 11 | 4/173 (2.3%) | 4 | 2/84 (2.4%) | 2 |
| Clostridium Difficile Colitis | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Cystitis Klebsiella | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Endocarditis | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Lower Respiratory Tract Infection Fungal | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Peritonitis | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Pneumonia | 1/159 (0.6%) | 1 | 6/173 (3.5%) | 6 | 0/84 (0%) | 0 |
| Pneumonia Bacterial | 1/159 (0.6%) | 1 | 3/173 (1.7%) | 3 | 1/84 (1.2%) | 1 |
| Pneumonia Klebsiella | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Sepsis | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Septic Shock | 4/159 (2.5%) | 4 | 4/173 (2.3%) | 5 | 2/84 (2.4%) | 2 |
| Soft Tissue Infection | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Staphylococcal Sepsis | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Systemic Bacterial Infection | 0/159 (0%) | 0 | 2/173 (1.2%) | 2 | 0/84 (0%) | 0 |
| Systemic Candida | 0/159 (0%) | 0 | 2/173 (1.2%) | 2 | 0/84 (0%) | 0 |
| Tracheobronchitis | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Ankle Fracture | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Femur Fracture | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Infusion Related Reaction | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Investigations | ||||||
| Alanine Aminotransferase Increased | 4/159 (2.5%) | 4 | 3/173 (1.7%) | 3 | 1/84 (1.2%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Hyperkalaemia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hypertriglyceridaemia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hyponatraemia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Rhabdomyolysis | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Nervous system disorders | ||||||
| Brain Oedema | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Carotid Artery Thrombosis | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Cerebrovascular Accident | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Hydrocephalus | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Hypoxic-Ischaemic Encephalopathy | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Ischaemic Stroke | 2/159 (1.3%) | 2 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute Kidney Injury | 2/159 (1.3%) | 2 | 4/173 (2.3%) | 4 | 0/84 (0%) | 0 |
| Renal Failure | 0/159 (0%) | 0 | 2/173 (1.2%) | 2 | 0/84 (0%) | 0 |
| Renal Impairment | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute Respiratory Failure | 0/159 (0%) | 0 | 4/173 (2.3%) | 4 | 0/84 (0%) | 0 |
| Hypoxia | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Organising Pneumonia | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumomediastinum | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Pneumothorax | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Pneumothorax Spontaneous | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Pulmonary Embolism | 1/159 (0.6%) | 1 | 2/173 (1.2%) | 2 | 2/84 (2.4%) | 2 |
| Respiratory Arrest | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Respiratory Distress | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Respiratory Failure | 6/159 (3.8%) | 6 | 5/173 (2.9%) | 5 | 3/84 (3.6%) | 3 |
| Vascular disorders | ||||||
| Deep Vein Thrombosis | 1/159 (0.6%) | 1 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Hypertensive Crisis | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
| Hypotension | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Peripheral Artery Occlusion | 0/159 (0%) | 0 | 1/173 (0.6%) | 1 | 0/84 (0%) | 0 |
| Thrombophlebitis Superficial | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Vena Cava Thrombosis | 0/159 (0%) | 0 | 0/173 (0%) | 0 | 1/84 (1.2%) | 1 |
| Venous Thrombosis Limb | 1/159 (0.6%) | 1 | 0/173 (0%) | 0 | 0/84 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Sarilumab 200 mg | Sarilumab 400 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 57/159 (35.8%) | 68/173 (39.3%) | 14/84 (16.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Neutropenia | 11/159 (6.9%) | 11 | 13/173 (7.5%) | 13 | 0/84 (0%) | 0 |
| Investigations | ||||||
| Alanine Aminotransferase Increased | 48/159 (30.2%) | 48 | 58/173 (33.5%) | 59 | 14/84 (16.7%) | 14 |
| Aspartate Aminotransferase Increased | 11/159 (6.9%) | 11 | 15/173 (8.7%) | 16 | 0/84 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | 800-633-1610 ext 6# |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT04327388
Other Study ID Numbers:
- EFC16844
- 2020-001162-12
- U1111-1249-6021
First Posted:
Mar 31, 2020
Last Update Posted:
Mar 17, 2022
Last Verified:
Mar 1, 2022