Trial Outcomes & Findings for A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19 (NCT NCT04402060)

NCT ID: NCT04402060

Last Updated: 2022-03-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

72 participants

Primary outcome timeframe

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

Results posted on

2022-03-23

Participant Flow

This 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).

The 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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	6	34	32
Overall Study Received Treatment	6	33	32
Overall Study COMPLETED	5	18	21
Overall Study NOT COMPLETED	1	16	11

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Death	1	12	7
Overall Study Adverse Event	0	0	1
Overall Study Withdrawal by Subject	0	1	2
Overall Study Sponsor Request	0	2	0
Overall Study Physician Decision	0	0	1
Overall Study Other	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: APL-9 n=6 Participants 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.	Part 2: APL-9 n=33 Participants 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.	Part 2: Control n=32 Participants 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 n=71 Participants Total of all reporting groups
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Unspecified	2 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Black/African American	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian/Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants	21 Participants n=7 Participants	18 Participants n=5 Participants	40 Participants n=4 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	15 Participants n=7 Participants	18 Participants n=5 Participants	39 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	18 Participants n=7 Participants	14 Participants n=5 Participants	32 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	17 Participants n=7 Participants	13 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	16 Participants n=7 Participants	19 Participants n=5 Participants	38 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=6 Participants 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.	Part 2: APL-9 n=33 Participants 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.	Part 2: Control n=32 Participants 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.
Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs TEAEs	4 Participants	23 Participants	22 Participants
Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Serious TEAEs	1 Participants	14 Participants	15 Participants

SECONDARY outcome

Timeframe: Part 2: Day 1 up to Day 58

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=32 Participants 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.	Part 2: APL-9 n=32 Participants 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.	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.
Hospital Length of Stay	21.5 days Interval 8.0 to 47.0	15.5 days Interval 9.0 to 30.0	—

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=32 Participants 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.	Part 2: APL-9 n=32 Participants 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.	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.
Overall Survival	NA days Interval 27.0 to The upper CI and median were not calculable due to insufficient events.	NA days The lower and upper CIs and median were not calculable due to insufficient events.	—

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=31 Participants 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.	Part 2: APL-9 n=29 Participants 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.	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.
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to Day 3	0.4 score on a scale Standard Deviation 2.17	1.2 score on a scale Standard Deviation 2.06	—
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to Day 5	0.6 score on a scale Standard Deviation 3.00	0.6 score on a scale Standard Deviation 2.48	—
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to Day 7	1.8 score on a scale Standard Deviation 3.97	0.9 score on a scale Standard Deviation 3.50	—
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to Day 11	1.7 score on a scale Standard Deviation 2.08	0.2 score on a scale Standard Deviation 5.97	—
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to Day 15	0.0 score on a scale Standard Deviation 2.83	-1.0 score on a scale Standard Deviation 2.83	—
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time Change to EOT	0.2 score on a scale Standard Deviation 3.56	0.6 score on a scale Standard Deviation 3.98	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=32 Participants 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.	Part 2: APL-9 n=32 Participants 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.	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.
Total Duration of Mechanical Ventilation	47.0 days The lower and upper CIs were not calculable due to insufficient events.	8.5 days Interval 7.0 to The upper CI was not calculable due to insufficient events.	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=32 Participants 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.	Part 2: APL-9 n=32 Participants 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.	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.
Total Duration of Oxygen Therapy	9.0 days Interval 5.0 to 47.0	8.0 days Interval 7.0 to The upper CI was not calculable due to insufficient events.	—

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=6 Participants 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.	Part 2: APL-9 n=33 Participants 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.	Part 2: Control n=31 Participants 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.
Serum Concentration of APL-9 Over Time Day 7	116.0 micrograms (μg)/mL) Standard Deviation 2.83	121.6 micrograms (μg)/mL) Standard Deviation 28.71	2.3 micrograms (μg)/mL) Standard Deviation 8.32
Serum Concentration of APL-9 Over Time Day 11	—	115.3 micrograms (μg)/mL) Standard Deviation 24.54	2.6 micrograms (μg)/mL) Standard Deviation 5.72
Serum Concentration of APL-9 Over Time Day 15	—	133.4 micrograms (μg)/mL) Standard Deviation 60.25	2.4 micrograms (μg)/mL) Standard Deviation 3.45
Serum Concentration of APL-9 Over Time EOT	114.5 micrograms (μg)/mL) Standard Deviation 16.21	95.0 micrograms (μg)/mL) Standard Deviation 34.19	0.0 micrograms (μg)/mL) Standard Deviation 0.00
Serum Concentration of APL-9 Over Time Day 1, Pre-dose	0.0 micrograms (μg)/mL) Standard Deviation 0.00	3.9 micrograms (μg)/mL) Standard Deviation 11.72	0.0 micrograms (μg)/mL) Standard Deviation 0.00
Serum Concentration of APL-9 Over Time Day 1, 10 mins	48.1 micrograms (μg)/mL) Standard Deviation 14.00	77.7 micrograms (μg)/mL) Standard Deviation 168.78	2.6 micrograms (μg)/mL) Standard Deviation 13.99
Serum Concentration of APL-9 Over Time Day 1, 2 hours	56.2 micrograms (μg)/mL) Standard Deviation 14.21	54.1 micrograms (μg)/mL) Standard Deviation 17.28	2.2 micrograms (μg)/mL) Standard Deviation 12.00
Serum Concentration of APL-9 Over Time Day 3	98.0 micrograms (μg)/mL) Standard Deviation 11.03	87.7 micrograms (μg)/mL) Standard Deviation 31.87	5.0 micrograms (μg)/mL) Standard Deviation 24.80
Serum Concentration of APL-9 Over Time Day 5	111.5 micrograms (μg)/mL) Standard Deviation 8.14	103.7 micrograms (μg)/mL) Standard Deviation 21.95	2.3 micrograms (μg)/mL) Standard Deviation 10.43

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=4 Participants 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.	Part 2: APL-9 n=14 Participants 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.	Part 2: Control n=18 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 C3	38.0 mg/deciliter (dL) Standard Deviation 11.17	91.4 mg/deciliter (dL) Standard Deviation 64.00	2.1 mg/deciliter (dL) Standard Deviation 35.32
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 C4	2.0 mg/deciliter (dL) Standard Deviation 19.30	-3.9 mg/deciliter (dL) Standard Deviation 16.34	0.2 mg/deciliter (dL) Standard Deviation 15.40

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=3 Participants 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.	Part 2: APL-9 n=19 Participants 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.	Part 2: Control n=19 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) C3a	-69.6 nanograms (ng)/mL Standard Deviation 16.35	-357.6 nanograms (ng)/mL Standard Deviation 785.69	-4.0 nanograms (ng)/mL Standard Deviation 240.70
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) C4a	-337.7 nanograms (ng)/mL Standard Deviation 371.70	-1560.8 nanograms (ng)/mL Standard Deviation 4821.35	-87.0 nanograms (ng)/mL Standard Deviation 1028.77
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) C5a	—	-6.9 nanograms (ng)/mL Standard Deviation 14.88	-3.9 nanograms (ng)/mL Standard Deviation 9.77
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) TCC	-143.1 nanograms (ng)/mL Standard Deviation 87.41	-127.4 nanograms (ng)/mL Standard Deviation 121.90	-12.2 nanograms (ng)/mL Standard Deviation 337.02

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=3 Participants 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.	Part 2: APL-9 n=19 Participants 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.	Part 2: Control n=19 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb	-0.6 μg/mL Standard Deviation 0.13	-0.9 μg/mL Standard Deviation 0.74	-0.1 μg/mL Standard Deviation 1.56

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=3 Participants 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.	Part 2: APL-9 n=19 Participants 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.	Part 2: Control n=18 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)	-157.7 Units (U)/mL Standard Deviation 26.84	-84.3 Units (U)/mL Standard Deviation 44.51	-2.3 Units (U)/mL Standard Deviation 43.72

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	Part 2: APL-9 n=4 Participants 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.	Part 2: Control n=7 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes	—	10325.4 % of reticulocytes Standard Deviation 20649.77	23929.1 % of reticulocytes Standard Deviation 87585.96

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	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.	Part 2: Control n=1 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes	—	—	0.0 10^9 cells/liter (L) Standard Deviation NA Standard deviation was not calculated due to only 1 subject analyzed

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=5 Participants 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.	Part 2: APL-9 n=16 Participants 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.	Part 2: Control n=23 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase	-464.6 U/L Standard Deviation 427.86	-135.2 U/L Standard Deviation 186.90	-106.1 U/L Standard Deviation 205.59

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=5 Participants 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.	Part 2: APL-9 n=17 Participants 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.	Part 2: Control n=24 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin D-dimer	-783.8 ng/mL Standard Deviation 607.57	217.2 ng/mL Standard Deviation 1218.54	907.9 ng/mL Standard Deviation 2986.71
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin Ferritin	-133.6 ng/mL Standard Deviation 80.80	-53.1 ng/mL Standard Deviation 650.97	-19.3 ng/mL Standard Deviation 694.52

SECONDARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=4 Participants 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.	Part 2: APL-9 n=14 Participants 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.	Part 2: Control n=22 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen Haptoglobin	—	-5435.4 mg/dL Standard Deviation 7571.18	-4554.0 mg/dL Standard Deviation 7756.60
Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen Fibrinogen	-147.3 mg/dL Standard Deviation 170.55	3995.1 mg/dL Standard Deviation 15113.49	-1348.2 mg/dL Standard Deviation 9726.66

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1: APL-9 n=4 Participants 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.	Part 2: APL-9 n=17 Participants 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.	Part 2: Control n=24 Participants 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.
Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)	-7.0 mg/dL Standard Deviation 8.67	6.4 mg/dL Standard Deviation 41.21	-3.1 mg/dL Standard Deviation 18.52

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	Part 2: APL-9 n=19 Participants 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.	Part 2: Control n=19 Participants 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.
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) TNFα	—	19.6 picograms/mL Standard Deviation 62.24	10.4 picograms/mL Standard Deviation 73.92
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) IL-1β	—	-0.6 picograms/mL Standard Deviation 7.15	-8.1 picograms/mL Standard Deviation 22.37
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) IL-6	—	203.6 picograms/mL Standard Deviation 602.54	71.3 picograms/mL Standard Deviation 499.84

Adverse Events

Part 1: APL-9

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Part 2: APL-9

Serious events: 14 serious events

Other events: 20 other events

Deaths: 13 deaths

Part 2: Control

Serious events: 15 serious events

Other events: 20 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Apellis Clinical Trial Information Line

Apellis Pharmaceuticals, Inc

Phone: 1-833-284-6361

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place