A Study of APL-9 in Adults With Mild to Moderate ARDS Due... | NCT04402060

Label	Type	Description	Intervention Names
180 mg APL-9 IV plus SOC	Experimental		Drug: APL-9
Isotonic saline plus SOC	Placebo Comparator		Other: Vehicle Control

Name	Type	Description	Arm Group Labels	Other Names
APL-9	Drug	Complement (C3) Inhibitor	180 mg APL-9 IV plus SOC
Vehicle Control

Measure	Description	Time Frame
Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	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.	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

Measure	Description	Time Frame
Hospital Length of Stay	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.	Part 2: Day 1 up to Day 58

Facility	Status	City	State	ZIP	Country	Contacts
University of California at San Francisco - Fresno		Fresno	California	93701	United States
California Pacific Medical Center

ID	Title	Description
FG000	Part 1: APL-9	Subjects 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 9, 2020	Dec 23, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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.

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.
OG002	Part 2: Control	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.

Units	Counts
Participants	OG0006 OG00133 OG00232

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0004 OG00123 OG00222

Serious TEAEs

Secondary

Hospital Length of Stay

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.

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.

Posted

Median

90% Confidence Interval

days

Part 2: Day 1 up to Day 58

ID	Title	Description
OG000	Part 2: APL-9	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.
OG001	Part 2: Control	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.

Secondary

Overall Survival

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.

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.

Posted

Median

90% Confidence Interval

days

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

ID	Title	Description
OG000	Part 2: APL-9	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.
OG001	Part 2: Control	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.

Secondary

Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time

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.

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.

Posted

Mean

Standard Deviation

score on a scale

Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)

ID	Title	Description
OG000	Part 2: APL-9 Plus SoC	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. 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.
OG001	Part 2: Vehicle Control Plus SoC

Secondary

Total Duration of Mechanical Ventilation

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.

Posted

Median

90% Confidence Interval

days

Part 2: Day 1 up to Day 58

ID	Title	Description
OG000	Part 2: APL-9	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.
OG001	Part 2: Control	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.

Secondary

Total Duration of Oxygen Therapy

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.

Posted

Median

90% Confidence Interval

days

Part 2: Day 1 up to Day 58

ID	Title	Description
OG000	Part 2: APL-9	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.
OG001	Part 2: Control	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.

Secondary

Serum Concentration of APL-9 Over Time

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.

The PK set included all subjects in the safety set and for whom at least 1 PK sample was evaluable.

Posted

Mean

Standard Deviation

micrograms (μg)/mL)

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)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4

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.

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.

Posted

Mean

Standard Deviation

mg/deciliter (dL)

Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)

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.

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.

Posted

Mean

Standard Deviation

nanograms (ng)/mL

Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb

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.

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.

Posted

Mean

Standard Deviation

μg/mL

Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)

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.

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.

Posted

Mean

Standard Deviation

Units (U)/mL

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes

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.

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.

Posted

Mean

Standard Deviation

% of reticulocytes

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes

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.

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.

Posted

Mean

Standard Deviation

10^9 cells/liter (L)

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase

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.

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.

Posted

Mean

Standard Deviation

U/L

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin

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.

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.

Posted

Mean

Standard Deviation

ng/mL

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen

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.

Posted

Mean

Standard Deviation

mg/dL

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)

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.

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.

Posted

Mean

Standard Deviation

mg/dL

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Secondary

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)

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.

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.

Posted

Mean

Standard Deviation

picograms/mL

Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)

ID	Title	Description
OG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
OG001	Part 2: APL-9	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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0020 affected32 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Bronchial secretion retention	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Septic shock	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pneumonia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0021 affected32 at risk
Sepsis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Cystitis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Lice infestation	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Nosocomial infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Urinary tract infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0021 affected32 at risk
Renal failure	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0020 affected32 at risk
Urinary retention	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Azotaemia	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Oliguria	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Distributive shock	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Hypertension	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0013 affected33 at risk EG0020 affected32 at risk
Shock	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Hypotension	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Phlebitis	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Poor peripheral circulation	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Venous thrombosis	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0023 affected32 at risk
Bradycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0020 affected32 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Sinus bradycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Tachycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0022 affected32 at risk
Blood bilirubin increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0020 affected32 at risk
C-reactive protein increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Fibrin D dimer increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Serum ferritin increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0022 affected32 at risk
Anion gap increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Antibiotic level below therapeutic	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood creatinine increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Blood glucose increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood pH increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Blood phosphorus decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood sodium decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood sodium increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Blood triglycerides increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood urea increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Brain natriuretic peptide increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Drug trough level	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected33 at risk EG0020 affected32 at risk
Electrocardiogram ST segment elevation	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Eosinophil count increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Haematocrit decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Haemoglobin decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
International normalised ratio increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Monocyte count increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Neutrophil count increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Oxygen saturation decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Platelet count increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Procalcitonin increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Transaminases increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Troponin increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
White blood cell count increased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0022 affected32 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Calcium deficiency	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Metabolic alkalosis	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Constipation	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0013 affected33 at risk EG0020 affected32 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0023 affected32 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected33 at risk EG0020 affected32 at risk
Ileus	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Vomiting	Gastrointestinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pyrexia	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0023 affected32 at risk
Catheter site pain	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Heparin-induced thrombocytopenia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Neutrophilia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Insomnia	Psychiatric disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0022 affected32 at risk
Agitation	Psychiatric disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Anxiety	Psychiatric disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hallucination, visual	Psychiatric disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Tissue injury	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Encephalopathy	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Presyncope	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk

ID	Term
D000086382	COVID-19
D018352	Coronavirus Infections
D045169	Severe Acute Respiratory Syndrome
D055371	Acute Lung Injury
D012128	Respiratory Distress Syndrome

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D055370	Lung Injury
D012120	Respiration Disorders

ID	Title	Description
BG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.
BG001	Part 2: APL-9	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.
BG002	Part 2: Control	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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: APL-9	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 resolution of ARDS (PaO2/FiO2 ratio >300 mm Hg), whichever occurred earlier. In addition, subjects received institutional SoC to treat their conditions.	1	6	1	6	3	6
EG001	Part 2: APL-9	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	13	33	14	33	20	33
EG002	Part 2: Control	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.	8	32	15	32	20	32

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0014 affected33 at risk EG0020 affected32 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0023 affected32 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0014 affected33 at risk EG0020 affected32 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0023 affected32 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0022 affected32 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Septic shock	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0014 affected33 at risk EG0021 affected32 at risk
Sepsis	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0022 affected32 at risk
Pneumonia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected33 at risk EG0020 affected32 at risk
COVID-19	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Cardiac valve vegetation	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Fungaemia	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Pneumonia pseudomonal	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pseudomonas infection	Infections and infestations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Distributive shock	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Embolism venous	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Shock	Vascular disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0021 affected32 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected33 at risk EG0022 affected32 at risk
Renal failure	Renal and urinary disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Bradycardia	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Pulseless electrical activity	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Right ventricular dilatation	Cardiac disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Pyrexia	General disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Blood pH decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Glomerular filtration rate decreased	Investigations	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected33 at risk EG0020 affected32 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA (23.0)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected33 at risk EG0021 affected32 at risk