A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19

Sponsor
Apellis Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04402060
Collaborator
(none)
72
Enrollment
24
Locations
2
Arms
8.6
Actual Duration (Months)
3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are hospitalized and require supplemental oxygen therapy with or without mechanical ventilation.

It is thought that COVID-19 activates the complement system, part of the immune system that responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has been designed to inhibit or block activation of part of the complement pathway, and potentially reduce inflammation in the lungs.

Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9 plus standard of care. Part 2 of the study is double-blind, randomized; participants will receive either APL-9 or the vehicle-control plus standard of care.

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19
Actual Study Start Date :
May 28, 2020
Actual Primary Completion Date :
Feb 13, 2021
Actual Study Completion Date :
Feb 13, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: 180 mg APL-9 IV plus SOC

Drug: APL-9
Complement (C3) Inhibitor

Placebo Comparator: Isotonic saline plus SOC

Other: Vehicle Control
Normal saline of equal volume to active arm

Outcome Measures

Primary Outcome Measures

  1. Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58]

    TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.

Secondary Outcome Measures

  1. Hospital Length of Stay [Part 2: Day 1 up to Day 58]

    Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.

  2. Overall Survival [Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])]

    Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.

  3. Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time [Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)]

    The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.

  4. Total Duration of Mechanical Ventilation [Part 2: Day 1 up to Day 58]

    Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.

  5. Total Duration of Oxygen Therapy [Part 2: Day 1 up to Day 58]

    Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.

  6. Serum Concentration of APL-9 Over Time [Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)]

    To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.

  7. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.

  8. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.

  9. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.

  10. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.

  11. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.

  12. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.

  13. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.

  14. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.

  15. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.

  16. Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.

  17. Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]

    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Be at least 18 years of age at time of informed consent

  • Diagnosis of active SARS CoV 2 infection using viral RNA or viral antigen within 7 days of screening

  • Respiratory failure requiring oxygen supplementation or either invasive or noninvasive mechanical ventilation with PaO2/FiO2 ratio >100 mm Hg. Respiratory failure cannot be fully explained by cardiac failure or fluid overload.

Exclusion Criteria:
  • Treatment with immune checkpoint inhibitors, or other immunomodulators within 3 months prior to study enrollment (however, treatment with convalescent plasma, steroids, IL-6 inhibitors, and antiviral agents is NOT excluded)

  • Active bacterial, fungal, or parasitic infection

  • History of neuromuscular degenerative disease (eg, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, or multiple sclerosis)

  • Current participation in an interventional clincial trial

  • Subjects who have, at screening, been on mechanical ventilation for >7 days Have evidence of kidney and liver failure at screening

  • Have a hereditary complement deficiency

  • Pregnancy or breastfeeding

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of California at San Francisco - FresnoFresnoCaliforniaUnited States93701
2California Pacific Medical CenterSan FranciscoCaliforniaUnited States94115
3Baptist Medical Center BeachesJacksonville BeachFloridaUnited States32250
4Westchester General HospitalMiamiFloridaUnited States40241
5Northwestern University, Feinberg School of MedicineChicagoIllinoisUnited States60611
6Loyola University Medical CenterMaywoodIllinoisUnited States60153
7Lutheran Health PhysiciansFort WayneIndianaUnited States46804
8University of Iowa Hospitals and ClinicsIowa CityIowaUnited States52242
9Norton Women's and Children's HospitalLouisvilleKentuckyUnited States40207
10Norton Audobon HospitalLouisvilleKentuckyUnited States40217
11Cambridge Medical TrialsAlexandriaLouisianaUnited States71301
12Ascension Providence HospitalSouthfieldMichiganUnited States48075
13Rutgers University - Robert Wood Johnson Medical SchoolNew BrunswickNew JerseyUnited States08903
14University at BuffaloBuffaloNew YorkUnited States14203
15Columbia UniversityNew YorkNew YorkUnited States10032
16Texas A&M College of Medicine - Scott and WhiteTempleTexasUnited States76508
17Hospital Angelina CaronCampina Grande Do SulParanáBrazil83430-000
18Irmandade da Santa Casa de Misericordia de Porto AlegrePorto AlegreRio Grande Do SulBrazil90020-090
19Hospital São Lucas da PUCRSPorto AlegreRio Grande Do SulBrazil91530-001
20Hospital Estadual Mario CovasSanto AndréSao PauloBrazil09190-615
21CEMEC - Centro Multidisciplinar de Estudos Clinicos LTDA EPPSão Bernardo Do CampoSao PauloBrazil0917-090
22Hospital Alemao Oswaldo CruzSão PauloSao PauloBrazil01323-020
23Hospital Santa MarcelinaSão PauloSao PauloBrazil08270-120
24UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESPBotucatuSão PauloBrazil18618-686

Sponsors and Collaborators

  • Apellis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04402060
Other Study ID Numbers:
  • APL9-COV-201
First Posted:
May 26, 2020
Last Update Posted:
Mar 23, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsThis was a randomized, double-blind, vehicle-controlled, multicenter, parallel-group Phase 1/2 study (with an initial open-label period) evaluating the safety and efficacy of APL-9 versus (vs) vehicle control as an add-on therapy to standard of care (SoC) in subjects who had respiratory failure, including mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).
Pre-assignment DetailThe study was conducted in 2 parts: Subjects in Part 1 received open-label APL-9 from Day 1 through Day 7 or resolution of ARDS. Subjects in Part 2 were randomly assigned 1:1 to blinded treatment with either APL-9 or vehicle control from Day 1 through Day 7 or up to and including Day 21, discontinuation of respiratory support or hospital discharge, whichever occurred latest. Extended treatment beyond Day 7 in Part 2 required certain criteria to be met and was at discretion of the Investigator.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial intravenous (IV) infusion of 180 milligram (mg) APL-9 in 50 milliliter (mL) of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2] ratio >300 millimeter [mm] of mercury [Hg]), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Period Title: Overall Study
STARTED63432
Received Treatment63332
COMPLETED51821
NOT COMPLETED11611

Baseline Characteristics

Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: ControlTotal
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Total of all reporting groups
Overall Participants6333271
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
6
100%
15
45.5%
18
56.3%
39
54.9%
>=65 years
0
0%
18
54.5%
14
43.8%
32
45.1%
Sex: Female, Male (Count of Participants)
Female
3
50%
17
51.5%
13
40.6%
33
46.5%
Male
3
50%
16
48.5%
19
59.4%
38
53.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
2
33.3%
11
33.3%
12
37.5%
25
35.2%
Not Hispanic or Latino
4
66.7%
13
39.4%
14
43.8%
31
43.7%
Unknown or Not Reported
0
0%
9
27.3%
6
18.8%
15
21.1%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
1
3%
2
6.3%
3
4.2%
Black/African American
3
50%
3
9.1%
2
6.3%
8
11.3%
Native Hawaiian/Pacific Islander
0
0%
0
0%
0
0%
0
0%
White
1
16.7%
21
63.6%
18
56.3%
40
56.3%
Unknown or Not Reported
0
0%
4
12.1%
2
6.3%
6
8.5%
Unspecified
2
33.3%
4
12.1%
8
25%
14
19.7%

Outcome Measures

1. Primary Outcome
TitleNumber of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
DescriptionTEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.
Time FrameFrom the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58

Outcome Measure Data

Analysis Population Description
The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants63332
TEAEs
4
66.7%
23
69.7%
22
68.8%
Serious TEAEs
1
16.7%
14
42.4%
15
46.9%
2. Secondary Outcome
TitleHospital Length of Stay
DescriptionHospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.
Time FramePart 2: Day 1 up to Day 58

Outcome Measure Data

Analysis Population Description
The full analysis set (FAS) included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.
Arm/Group TitlePart 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants3232
Median (90% Confidence Interval) [days]
21.5
15.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: APL-9, Part 2: APL-9
Comments P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% confidence interval (CI) was based on the Wald method.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.82
Comments
MethodLog Rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.98
Confidence Interval (2-Sided) 90%
0.63 to 1.51
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
TitleOverall Survival
DescriptionOverall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
Time FramePart 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])

Outcome Measure Data

Analysis Population Description
The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.
Arm/Group TitlePart 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants3232
Median (90% Confidence Interval) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: APL-9, Part 2: APL-9
Comments P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.36
Comments
MethodLog Rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value1.62
Confidence Interval (2-Sided) 90%
0.77 to 3.40
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
TitleChange From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time
DescriptionThe SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.
Time FramePart 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. Only subjects with values at both Baseline and the specified visit were included in the analysis.
Arm/Group TitlePart 2: APL-9 Plus SoCPart 2: Vehicle Control Plus SoC
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. Follow-up safety assessments were collected 30 days following the last dose of study treatment (with a +7-day window). All subjects received SoC independent of their randomization.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. Follow-up safety assessments were collected 30 days following the last dose of study treatment (with a +7-day window). All subjects received SoC independent of their randomization.
Measure Participants3129
Change to Day 3
0.4
(2.17)
1.2
(2.06)
Change to Day 5
0.6
(3.00)
0.6
(2.48)
Change to Day 7
1.8
(3.97)
0.9
(3.50)
Change to Day 11
1.7
(2.08)
0.2
(5.97)
Change to Day 15
0.0
(2.83)
-1.0
(2.83)
Change to EOT
0.2
(3.56)
0.6
(3.98)
5. Secondary Outcome
TitleTotal Duration of Mechanical Ventilation
DescriptionTotal duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.
Time FramePart 2: Day 1 up to Day 58

Outcome Measure Data

Analysis Population Description
The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.
Arm/Group TitlePart 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants3232
Median (90% Confidence Interval) [days]
47.0
8.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: APL-9, Part 2: APL-9
Comments P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.03
Comments
MethodLog Rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.09
Confidence Interval (2-Sided) 90%
0.01 to 0.51
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
TitleTotal Duration of Oxygen Therapy
DescriptionTotal duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.
Time FramePart 2: Day 1 up to Day 58

Outcome Measure Data

Analysis Population Description
The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only.
Arm/Group TitlePart 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants3232
Median (90% Confidence Interval) [days]
9.0
8.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: APL-9, Part 2: APL-9
Comments P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesisp-Value0.93
Comments
MethodLog Rank
Comments
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value1.09
Confidence Interval (2-Sided) 90%
0.69 to 1.72
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
TitleSerum Concentration of APL-9 Over Time
DescriptionTo evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.
Time FramePart 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PK set included all subjects in the safety set and for whom at least 1 PK sample was evaluable.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants63331
Day 1, Pre-dose
0.0
(0.00)
3.9
(11.72)
0.0
(0.00)
Day 1, 10 mins
48.1
(14.00)
77.7
(168.78)
2.6
(13.99)
Day 1, 2 hours
56.2
(14.21)
54.1
(17.28)
2.2
(12.00)
Day 3
98.0
(11.03)
87.7
(31.87)
5.0
(24.80)
Day 5
111.5
(8.14)
103.7
(21.95)
2.3
(10.43)
Day 7
116.0
(2.83)
121.6
(28.71)
2.3
(8.32)
Day 11
115.3
(24.54)
2.6
(5.72)
Day 15
133.4
(60.25)
2.4
(3.45)
EOT
114.5
(16.21)
95.0
(34.19)
0.0
(0.00)
8. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4
DescriptionTo evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.
Time FramePart 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants41418
C3
38.0
(11.17)
91.4
(64.00)
2.1
(35.32)
C4
2.0
(19.30)
-3.9
(16.34)
0.2
(15.40)
9. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.
Time FramePart 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Note: C5a was only measured in Part 2 because this biomarker was added in APL9-COV-201 Protocol Amendment 2 which was after the last subject in Part 1 finished the last study dose. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants31919
C3a
-69.6
(16.35)
-357.6
(785.69)
-4.0
(240.70)
C4a
-337.7
(371.70)
-1560.8
(4821.35)
-87.0
(1028.77)
C5a
-6.9
(14.88)
-3.9
(9.77)
TCC
-143.1
(87.41)
-127.4
(121.90)
-12.2
(337.02)
10. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.
Time FramePart 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants31919
Mean (Standard Deviation) [μg/mL]
-0.6
(0.13)
-0.9
(0.74)
-0.1
(1.56)
11. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants31918
Mean (Standard Deviation) [Units (U)/mL]
-157.7
(26.84)
-84.3
(44.51)
-2.3
(43.72)
12. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants047
Mean (Standard Deviation) [% of reticulocytes]
10325.4
(20649.77)
23929.1
(87585.96)
13. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants001
Mean (Standard Deviation) [10^9 cells/liter (L)]
0.0
(NA)
14. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants51623
Mean (Standard Deviation) [U/L]
-464.6
(427.86)
-135.2
(186.90)
-106.1
(205.59)
15. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants51724
D-dimer
-783.8
(607.57)
217.2
(1218.54)
907.9
(2986.71)
Ferritin
-133.6
(80.80)
-53.1
(650.97)
-19.3
(694.52)
16. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants41422
Haptoglobin
-5435.4
(7571.18)
-4554.0
(7756.60)
Fibrinogen
-147.3
(170.55)
3995.1
(15113.49)
-1348.2
(9726.66)
17. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants41724
Mean (Standard Deviation) [mg/dL]
-7.0
(8.67)
6.4
(41.21)
-3.1
(18.52)
18. Secondary Outcome
TitleChange From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6)
DescriptionTo evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.
Time FramePart 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

Outcome Measure Data

Analysis Population Description
The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
Measure Participants01919
TNFα
19.6
(62.24)
10.4
(73.92)
IL-1β
-0.6
(7.15)
-8.1
(22.37)
IL-6
203.6
(602.54)
71.3
(499.84)

Adverse Events

Time FrameFrom the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58.
Adverse Event Reporting Description The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received.
Arm/Group TitlePart 1: APL-9Part 2: APL-9Part 2: Control
Arm/Group DescriptionSubjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditionsSubjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions.
All Cause Mortality
Part 1: APL-9Part 2: APL-9Part 2: Control
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/6 (16.7%) 13/33 (39.4%) 8/32 (25%)
Serious Adverse Events
Part 1: APL-9Part 2: APL-9Part 2: Control
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/6 (16.7%) 14/33 (42.4%) 15/32 (46.9%)
Blood and lymphatic system disorders
Thrombocytopenia0/6 (0%) 1/33 (3%) 0/32 (0%)
Cardiac disorders
Atrial fibrillation0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Bradycardia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Pulseless electrical activity0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Right ventricular dilatation0/6 (0%) 0/33 (0%) 1/32 (3.1%)
General disorders
Multiple organ dysfunction syndrome0/6 (0%) 1/33 (3%) 0/32 (0%)
Pyrexia0/6 (0%) 1/33 (3%) 0/32 (0%)
Infections and infestations
Septic shock0/6 (0%) 4/33 (12.1%) 1/32 (3.1%)
Sepsis0/6 (0%) 1/33 (3%) 2/32 (6.3%)
Pneumonia0/6 (0%) 2/33 (6.1%) 0/32 (0%)
COVID-190/6 (0%) 1/33 (3%) 0/32 (0%)
Cardiac valve vegetation0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Fungaemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Pneumonia bacterial0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Pneumonia pseudomonal0/6 (0%) 1/33 (3%) 0/32 (0%)
Pseudomonas infection0/6 (0%) 1/33 (3%) 0/32 (0%)
Investigations
Blood pH decreased0/6 (0%) 1/33 (3%) 0/32 (0%)
Glomerular filtration rate decreased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Metabolism and nutrition disorders
Hypernatraemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Nervous system disorders
Metabolic encephalopathy0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Renal and urinary disorders
Acute kidney injury1/6 (16.7%) 1/33 (3%) 2/32 (6.3%)
Renal failure0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure1/6 (16.7%) 4/33 (12.1%) 0/32 (0%)
Acute respiratory failure0/6 (0%) 1/33 (3%) 3/32 (9.4%)
Dyspnoea0/6 (0%) 4/33 (12.1%) 0/32 (0%)
Hypoxia0/6 (0%) 0/33 (0%) 3/32 (9.4%)
Pneumothorax0/6 (0%) 0/33 (0%) 2/32 (6.3%)
Acute respiratory distress syndrome0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Aspiration0/6 (0%) 1/33 (3%) 0/32 (0%)
Pulmonary embolism0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Vascular disorders
Distributive shock0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Embolism venous0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Shock0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Other (Not Including Serious) Adverse Events
Part 1: APL-9Part 2: APL-9Part 2: Control
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total3/6 (50%) 20/33 (60.6%) 20/32 (62.5%)
Blood and lymphatic system disorders
Anaemia0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Thrombocytopenia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Blood loss anaemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Heparin-induced thrombocytopenia0/6 (0%) 1/33 (3%) 0/32 (0%)
Leukocytosis0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Neutrophilia0/6 (0%) 1/33 (3%) 0/32 (0%)
Cardiac disorders
Atrial fibrillation0/6 (0%) 1/33 (3%) 3/32 (9.4%)
Bradycardia0/6 (0%) 2/33 (6.1%) 0/32 (0%)
Cardiogenic shock0/6 (0%) 1/33 (3%) 0/32 (0%)
Sinus bradycardia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Sinus tachycardia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Tachycardia0/6 (0%) 1/33 (3%) 0/32 (0%)
Gastrointestinal disorders
Constipation0/6 (0%) 3/33 (9.1%) 0/32 (0%)
Dysphagia0/6 (0%) 0/33 (0%) 3/32 (9.4%)
Abdominal pain upper0/6 (0%) 1/33 (3%) 0/32 (0%)
Diarrhoea0/6 (0%) 1/33 (3%) 0/32 (0%)
Haematochezia1/6 (16.7%) 0/33 (0%) 0/32 (0%)
Ileus0/6 (0%) 1/33 (3%) 0/32 (0%)
Vomiting0/6 (0%) 1/33 (3%) 0/32 (0%)
General disorders
Pyrexia0/6 (0%) 1/33 (3%) 3/32 (9.4%)
Catheter site pain0/6 (0%) 1/33 (3%) 0/32 (0%)
Hepatobiliary disorders
Hepatic failure0/6 (0%) 1/33 (3%) 0/32 (0%)
Infections and infestations
Septic shock0/6 (0%) 1/33 (3%) 0/32 (0%)
Pneumonia0/6 (0%) 2/33 (6.1%) 1/32 (3.1%)
Sepsis0/6 (0%) 1/33 (3%) 0/32 (0%)
Cystitis0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Lice infestation0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Nosocomial infection0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Pneumonia staphylococcal0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Urinary tract infection0/6 (0%) 1/33 (3%) 0/32 (0%)
Vulvovaginal mycotic infection0/6 (0%) 1/33 (3%) 0/32 (0%)
Injury, poisoning and procedural complications
Contusion0/6 (0%) 1/33 (3%) 0/32 (0%)
Fall0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Tissue injury0/6 (0%) 1/33 (3%) 0/32 (0%)
Vascular access complication0/6 (0%) 1/33 (3%) 0/32 (0%)
Investigations
Blood lactate dehydrogenase increased0/6 (0%) 1/33 (3%) 2/32 (6.3%)
Blood bilirubin increased0/6 (0%) 2/33 (6.1%) 0/32 (0%)
C-reactive protein increased0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Fibrin D dimer increased0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Serum ferritin increased0/6 (0%) 0/33 (0%) 2/32 (6.3%)
Anion gap increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Antibiotic level below therapeutic0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood creatine phosphokinase increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood creatinine increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Blood glucose increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood pH increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Blood phosphorus decreased0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood sodium decreased0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood sodium increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Blood triglycerides increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Blood urea increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Brain natriuretic peptide increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Drug trough level0/6 (0%) 1/33 (3%) 0/32 (0%)
Electrocardiogram QT prolonged1/6 (16.7%) 0/33 (0%) 0/32 (0%)
Electrocardiogram ST segment elevation0/6 (0%) 1/33 (3%) 0/32 (0%)
Eosinophil count increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Haematocrit decreased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Haemoglobin decreased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
International normalised ratio increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Monocyte count increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Neutrophil count increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Oxygen saturation decreased0/6 (0%) 1/33 (3%) 0/32 (0%)
Platelet count increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Procalcitonin increased0/6 (0%) 1/33 (3%) 0/32 (0%)
Transaminases increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Troponin increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
White blood cell count increased0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Metabolism and nutrition disorders
Hypernatraemia0/6 (0%) 0/33 (0%) 2/32 (6.3%)
Metabolic acidosis0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Alkalosis0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Calcium deficiency0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Hypercalcaemia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Hyperkalaemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Hypertriglyceridaemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Hypoglycaemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Hyponatraemia0/6 (0%) 1/33 (3%) 0/32 (0%)
Metabolic alkalosis0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Nervous system disorders
Encephalopathy0/6 (0%) 1/33 (3%) 0/32 (0%)
Presyncope0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Toxic encephalopathy0/6 (0%) 1/33 (3%) 0/32 (0%)
Psychiatric disorders
Insomnia0/6 (0%) 1/33 (3%) 2/32 (6.3%)
Agitation0/6 (0%) 1/33 (3%) 0/32 (0%)
Anxiety0/6 (0%) 1/33 (3%) 0/32 (0%)
Hallucination, visual0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Renal and urinary disorders
Acute kidney injury0/6 (0%) 2/33 (6.1%) 1/32 (3.1%)
Renal failure0/6 (0%) 2/33 (6.1%) 0/32 (0%)
Urinary retention0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Azotaemia0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Oliguria0/6 (0%) 1/33 (3%) 0/32 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax0/6 (0%) 2/33 (6.1%) 0/32 (0%)
Epistaxis1/6 (16.7%) 1/33 (3%) 0/32 (0%)
Pulmonary embolism0/6 (0%) 1/33 (3%) 0/32 (0%)
Bronchial secretion retention0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Hypercapnia0/6 (0%) 1/33 (3%) 0/32 (0%)
Pneumomediastinum0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Respiratory acidosis0/6 (0%) 1/33 (3%) 0/32 (0%)
Respiratory disorder0/6 (0%) 1/33 (3%) 0/32 (0%)
Skin and subcutaneous tissue disorders
Rash1/6 (16.7%) 0/33 (0%) 1/32 (3.1%)
Dermatitis diaper0/6 (0%) 1/33 (3%) 0/32 (0%)
Rash maculo-papular0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Skin ulcer0/6 (0%) 1/33 (3%) 0/32 (0%)
Subcutaneous emphysema0/6 (0%) 1/33 (3%) 0/32 (0%)
Vascular disorders
Distributive shock0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Hypertension0/6 (0%) 3/33 (9.1%) 0/32 (0%)
Shock0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Deep vein thrombosis0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Hypotension0/6 (0%) 1/33 (3%) 1/32 (3.1%)
Phlebitis0/6 (0%) 0/33 (0%) 1/32 (3.1%)
Poor peripheral circulation0/6 (0%) 1/33 (3%) 0/32 (0%)
Venous thrombosis0/6 (0%) 1/33 (3%) 0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleApellis Clinical Trial Information Line
OrganizationApellis Pharmaceuticals, Inc
Phone1-833-284-6361
Emailclinicaltrials@apellis.com
Responsible Party:
Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04402060
Other Study ID Numbers:
  • APL9-COV-201
First Posted:
May 26, 2020
Last Update Posted:
Mar 23, 2022
Last Verified:
Mar 1, 2022