A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19
Sponsor
Apellis Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04402060
Collaborator
(none)
72
24
2
8.6
3
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are hospitalized and require supplemental oxygen therapy with or without mechanical ventilation.
It is thought that COVID-19 activates the complement system, part of the immune system that responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has been designed to inhibit or block activation of part of the complement pathway, and potentially reduce inflammation in the lungs.
Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9 plus standard of care. Part 2 of the study is double-blind, randomized; participants will receive either APL-9 or the vehicle-control plus standard of care.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
72 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19
Actual Study Start Date
:
May 28, 2020
Actual Primary Completion Date
:
Feb 13, 2021
Actual Study Completion Date
:
Feb 13, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 180 mg APL-9 IV plus SOC
|
Drug: APL-9
Complement (C3) Inhibitor
|
| Placebo Comparator: Isotonic saline plus SOC
|
Other: Vehicle Control
Normal saline of equal volume to active arm
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58]
TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.
Secondary Outcome Measures
- Hospital Length of Stay [Part 2: Day 1 up to Day 58]
Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.
- Overall Survival [Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])]
Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
- Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time [Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)]
The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.
- Total Duration of Mechanical Ventilation [Part 2: Day 1 up to Day 58]
Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.
- Total Duration of Oxygen Therapy [Part 2: Day 1 up to Day 58]
Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.
- Serum Concentration of APL-9 Over Time [Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21)]
To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.
- Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.
- Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.
- Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb [Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.
- Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.
- Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.
- Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.
- Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.
- Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.
- Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.
- Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.
- Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6) [Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)]
To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Be at least 18 years of age at time of informed consent
-
Diagnosis of active SARS CoV 2 infection using viral RNA or viral antigen within 7 days of screening
-
Respiratory failure requiring oxygen supplementation or either invasive or noninvasive mechanical ventilation with PaO2/FiO2 ratio >100 mm Hg. Respiratory failure cannot be fully explained by cardiac failure or fluid overload.
Exclusion Criteria:
-
Treatment with immune checkpoint inhibitors, or other immunomodulators within 3 months prior to study enrollment (however, treatment with convalescent plasma, steroids, IL-6 inhibitors, and antiviral agents is NOT excluded)
-
Active bacterial, fungal, or parasitic infection
-
History of neuromuscular degenerative disease (eg, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, or multiple sclerosis)
-
Current participation in an interventional clincial trial
-
Subjects who have, at screening, been on mechanical ventilation for >7 days Have evidence of kidney and liver failure at screening
-
Have a hereditary complement deficiency
-
Pregnancy or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California at San Francisco - Fresno | Fresno | California | United States | 93701 |
| 2 | California Pacific Medical Center | San Francisco | California | United States | 94115 |
| 3 | Baptist Medical Center Beaches | Jacksonville Beach | Florida | United States | 32250 |
| 4 | Westchester General Hospital | Miami | Florida | United States | 40241 |
| 5 | Northwestern University, Feinberg School of Medicine | Chicago | Illinois | United States | 60611 |
| 6 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 7 | Lutheran Health Physicians | Fort Wayne | Indiana | United States | 46804 |
| 8 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 9 | Norton Women's and Children's Hospital | Louisville | Kentucky | United States | 40207 |
| 10 | Norton Audobon Hospital | Louisville | Kentucky | United States | 40217 |
| 11 | Cambridge Medical Trials | Alexandria | Louisiana | United States | 71301 |
| 12 | Ascension Providence Hospital | Southfield | Michigan | United States | 48075 |
| 13 | Rutgers University - Robert Wood Johnson Medical School | New Brunswick | New Jersey | United States | 08903 |
| 14 | University at Buffalo | Buffalo | New York | United States | 14203 |
| 15 | Columbia University | New York | New York | United States | 10032 |
| 16 | Texas A&M College of Medicine - Scott and White | Temple | Texas | United States | 76508 |
| 17 | Hospital Angelina Caron | Campina Grande Do Sul | Paraná | Brazil | 83430-000 |
| 18 | Irmandade da Santa Casa de Misericordia de Porto Alegre | Porto Alegre | Rio Grande Do Sul | Brazil | 90020-090 |
| 19 | Hospital São Lucas da PUCRS | Porto Alegre | Rio Grande Do Sul | Brazil | 91530-001 |
| 20 | Hospital Estadual Mario Covas | Santo André | Sao Paulo | Brazil | 09190-615 |
| 21 | CEMEC - Centro Multidisciplinar de Estudos Clinicos LTDA EPP | São Bernardo Do Campo | Sao Paulo | Brazil | 0917-090 |
| 22 | Hospital Alemao Oswaldo Cruz | São Paulo | Sao Paulo | Brazil | 01323-020 |
| 23 | Hospital Santa Marcelina | São Paulo | Sao Paulo | Brazil | 08270-120 |
| 24 | UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP | Botucatu | São Paulo | Brazil | 18618-686 |
Sponsors and Collaborators
- Apellis Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04402060
Other Study ID Numbers:
- APL9-COV-201
First Posted:
May 26, 2020
Last Update Posted:
Mar 23, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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). |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Period Title: Overall Study | |||
| STARTED | 6 | 34 | 32 |
| Received Treatment | 6 | 33 | 32 |
| COMPLETED | 5 | 18 | 21 |
| NOT COMPLETED | 1 | 16 | 11 |
Baseline Characteristics
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Total of all reporting groups |
| Overall Participants | 6 | 33 | 32 | 71 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
6
100%
|
15
45.5%
|
18
56.3%
|
39
54.9%
|
| >=65 years |
0
0%
|
18
54.5%
|
14
43.8%
|
32
45.1%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
50%
|
17
51.5%
|
13
40.6%
|
33
46.5%
|
| Male |
3
50%
|
16
48.5%
|
19
59.4%
|
38
53.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
2
33.3%
|
11
33.3%
|
12
37.5%
|
25
35.2%
|
| Not Hispanic or Latino |
4
66.7%
|
13
39.4%
|
14
43.8%
|
31
43.7%
|
| Unknown or Not Reported |
0
0%
|
9
27.3%
|
6
18.8%
|
15
21.1%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| American Indian/Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
3%
|
2
6.3%
|
3
4.2%
|
| Black/African American |
3
50%
|
3
9.1%
|
2
6.3%
|
8
11.3%
|
| Native Hawaiian/Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
1
16.7%
|
21
63.6%
|
18
56.3%
|
40
56.3%
|
| Unknown or Not Reported |
0
0%
|
4
12.1%
|
2
6.3%
|
6
8.5%
|
| Unspecified |
2
33.3%
|
4
12.1%
|
8
25%
|
14
19.7%
|
Outcome Measures
| Title | Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 6 | 33 | 32 |
| TEAEs |
4
66.7%
|
23
69.7%
|
22
68.8%
|
| Serious TEAEs |
1
16.7%
|
14
42.4%
|
15
46.9%
|
| Title | Hospital Length of Stay |
|---|---|
| Description | 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. |
| Time Frame | Part 2: Day 1 up to Day 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. |
| Arm/Group Title | Part 2: APL-9 | Part 2: Control |
|---|---|---|
| Arm/Group Description | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 32 | 32 |
| Median (90% Confidence Interval) [days] |
21.5
|
15.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: APL-9, Part 2: APL-9 |
|---|---|---|
| Comments | P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% confidence interval (CI) was based on the Wald method. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.82 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 90% 0.63 to 1.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival |
|---|---|
| Description | 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. |
| Time Frame | Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. |
| Arm/Group Title | Part 2: APL-9 | Part 2: Control |
|---|---|---|
| Arm/Group Description | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 32 | 32 |
| Median (90% Confidence Interval) [days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: APL-9, Part 2: APL-9 |
|---|---|---|
| Comments | P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.36 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.62 | |
| Confidence Interval |
(2-Sided) 90% 0.77 to 3.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. Only subjects with values at both Baseline and the specified visit were included in the analysis. |
| Arm/Group Title | Part 2: APL-9 Plus SoC | Part 2: Vehicle Control Plus SoC |
|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. Follow-up safety assessments were collected 30 days following the last dose of study treatment (with a +7-day window). All subjects received SoC independent of their randomization. |
| Measure Participants | 31 | 29 |
| Change to Day 3 |
0.4
(2.17)
|
1.2
(2.06)
|
| Change to Day 5 |
0.6
(3.00)
|
0.6
(2.48)
|
| Change to Day 7 |
1.8
(3.97)
|
0.9
(3.50)
|
| Change to Day 11 |
1.7
(2.08)
|
0.2
(5.97)
|
| Change to Day 15 |
0.0
(2.83)
|
-1.0
(2.83)
|
| Change to EOT |
0.2
(3.56)
|
0.6
(3.98)
|
| Title | Total Duration of Mechanical Ventilation |
|---|---|
| Description | 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. |
| Time Frame | Part 2: Day 1 up to Day 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomized subjects who received at least 1 dose of study drug. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. |
| Arm/Group Title | Part 2: APL-9 | Part 2: Control |
|---|---|---|
| Arm/Group Description | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 32 | 32 |
| Median (90% Confidence Interval) [days] |
47.0
|
8.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: APL-9, Part 2: APL-9 |
|---|---|---|
| Comments | P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.03 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 90% 0.01 to 0.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Total Duration of Oxygen Therapy |
|---|---|
| Description | 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. |
| Time Frame | Part 2: Day 1 up to Day 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS included all randomized subjects who received at least 1 dose of study treatment. The analyses using the FAS were based upon the actual treatment allocated. Analysis was pre-specified in Part 2 only. |
| Arm/Group Title | Part 2: APL-9 | Part 2: Control |
|---|---|---|
| Arm/Group Description | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 32 | 32 |
| Median (90% Confidence Interval) [days] |
9.0
|
8.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 1: APL-9, Part 2: APL-9 |
|---|---|---|
| Comments | P-value was from a 2-sided stratified Log-rank test by the randomization stratification factors (need of mechanical ventilation [yes vs no] and age [<65 years vs ≥65 years]) at 0.1 significant level for evaluation of treatment difference. Hazard ratio was obtained from a Cox regression model with treatment and the randomization stratification factors as fixed factors and 90% CI was based on the Wald method. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.93 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 90% 0.69 to 1.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Serum Concentration of APL-9 Over Time |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK set included all subjects in the safety set and for whom at least 1 PK sample was evaluable. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 6 | 33 | 31 |
| Day 1, Pre-dose |
0.0
(0.00)
|
3.9
(11.72)
|
0.0
(0.00)
|
| Day 1, 10 mins |
48.1
(14.00)
|
77.7
(168.78)
|
2.6
(13.99)
|
| Day 1, 2 hours |
56.2
(14.21)
|
54.1
(17.28)
|
2.2
(12.00)
|
| Day 3 |
98.0
(11.03)
|
87.7
(31.87)
|
5.0
(24.80)
|
| Day 5 |
111.5
(8.14)
|
103.7
(21.95)
|
2.3
(10.43)
|
| Day 7 |
116.0
(2.83)
|
121.6
(28.71)
|
2.3
(8.32)
|
| Day 11 |
115.3
(24.54)
|
2.6
(5.72)
|
|
| Day 15 |
133.4
(60.25)
|
2.4
(3.45)
|
|
| EOT |
114.5
(16.21)
|
95.0
(34.19)
|
0.0
(0.00)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 4 | 14 | 18 |
| C3 |
38.0
(11.17)
|
91.4
(64.00)
|
2.1
(35.32)
|
| C4 |
2.0
(19.30)
|
-3.9
(16.34)
|
0.2
(15.40)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Note: C5a was only measured in Part 2 because this biomarker was added in APL9-COV-201 Protocol Amendment 2 which was after the last subject in Part 1 finished the last study dose. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 3 | 19 | 19 |
| C3a |
-69.6
(16.35)
|
-357.6
(785.69)
|
-4.0
(240.70)
|
| C4a |
-337.7
(371.70)
|
-1560.8
(4821.35)
|
-87.0
(1028.77)
|
| C5a |
-6.9
(14.88)
|
-3.9
(9.77)
|
|
| TCC |
-143.1
(87.41)
|
-127.4
(121.90)
|
-12.2
(337.02)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 3 | 19 | 19 |
| Mean (Standard Deviation) [μg/mL] |
-0.6
(0.13)
|
-0.9
(0.74)
|
-0.1
(1.56)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50) |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 3 | 19 | 18 |
| Mean (Standard Deviation) [Units (U)/mL] |
-157.7
(26.84)
|
-84.3
(44.51)
|
-2.3
(43.72)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 0 | 4 | 7 |
| Mean (Standard Deviation) [% of reticulocytes] |
10325.4
(20649.77)
|
23929.1
(87585.96)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 0 | 0 | 1 |
| Mean (Standard Deviation) [10^9 cells/liter (L)] |
0.0
(NA)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 5 | 16 | 23 |
| Mean (Standard Deviation) [U/L] |
-464.6
(427.86)
|
-135.2
(186.90)
|
-106.1
(205.59)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 5 | 17 | 24 |
| D-dimer |
-783.8
(607.57)
|
217.2
(1218.54)
|
907.9
(2986.71)
|
| Ferritin |
-133.6
(80.80)
|
-53.1
(650.97)
|
-19.3
(694.52)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen |
|---|---|
| Description | To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 4 | 14 | 22 |
| Haptoglobin |
-5435.4
(7571.18)
|
-4554.0
(7756.60)
|
|
| Fibrinogen |
-147.3
(170.55)
|
3995.1
(15113.49)
|
-1348.2
(9726.66)
|
| Title | Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP) |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 4 | 17 | 24 |
| Mean (Standard Deviation) [mg/dL] |
-7.0
(8.67)
|
6.4
(41.21)
|
-3.1
(18.52)
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PD set included all subjects in the safety set with at least 1 PD evaluation. Only subjects with values at both Baseline and the EOT visit were included in the analysis. |
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control |
|---|---|---|---|
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. |
| Measure Participants | 0 | 19 | 19 |
| TNFα |
19.6
(62.24)
|
10.4
(73.92)
|
|
| IL-1β |
-0.6
(7.15)
|
-8.1
(22.37)
|
|
| IL-6 |
203.6
(602.54)
|
71.3
(499.84)
|
Adverse Events
| Time Frame | 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. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The safety set included all subjects who received at least 1 dose of study drug. Subjects were analyzed according to the actual treatment they received. | |||||
| Arm/Group Title | Part 1: APL-9 | Part 2: APL-9 | Part 2: Control | |||
| Arm/Group Description | 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. | Subjects received an initial IV infusion of 180 mg APL-9 in 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 180 mg APL-9 in 250 mL saline at the rate of 15 mg/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions | Subjects received an initial IV infusion of 50 mL of saline once over a 10-minute period, followed within 1 hour by continuous IV infusion of 250 mL saline at the rate of 21 mL/hour until Day 7 or up to and including Day 21, discontinuation of respiratory support (supplemental oxygen or mechanical ventilation), or hospital discharge, whichever occurred latest. In addition, subjects received institutional SoC to treat their conditions. | |||
All Cause Mortality |
||||||
| Part 1: APL-9 | Part 2: APL-9 | Part 2: Control | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 13/33 (39.4%) | 8/32 (25%) | |||
Serious Adverse Events |
||||||
| Part 1: APL-9 | Part 2: APL-9 | Part 2: Control | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 14/33 (42.4%) | 15/32 (46.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Thrombocytopenia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Bradycardia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Pulseless electrical activity | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Right ventricular dilatation | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| General disorders | ||||||
| Multiple organ dysfunction syndrome | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pyrexia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Infections and infestations | ||||||
| Septic shock | 0/6 (0%) | 4/33 (12.1%) | 1/32 (3.1%) | |||
| Sepsis | 0/6 (0%) | 1/33 (3%) | 2/32 (6.3%) | |||
| Pneumonia | 0/6 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||
| COVID-19 | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Cardiac valve vegetation | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Fungaemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pneumonia bacterial | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Pneumonia pseudomonal | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pseudomonas infection | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Investigations | ||||||
| Blood pH decreased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Glomerular filtration rate decreased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypernatraemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Nervous system disorders | ||||||
| Metabolic encephalopathy | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/6 (16.7%) | 1/33 (3%) | 2/32 (6.3%) | |||
| Renal failure | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory failure | 1/6 (16.7%) | 4/33 (12.1%) | 0/32 (0%) | |||
| Acute respiratory failure | 0/6 (0%) | 1/33 (3%) | 3/32 (9.4%) | |||
| Dyspnoea | 0/6 (0%) | 4/33 (12.1%) | 0/32 (0%) | |||
| Hypoxia | 0/6 (0%) | 0/33 (0%) | 3/32 (9.4%) | |||
| Pneumothorax | 0/6 (0%) | 0/33 (0%) | 2/32 (6.3%) | |||
| Acute respiratory distress syndrome | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Aspiration | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pulmonary embolism | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Vascular disorders | ||||||
| Distributive shock | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Embolism venous | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Shock | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Part 1: APL-9 | Part 2: APL-9 | Part 2: Control | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 20/33 (60.6%) | 20/32 (62.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Thrombocytopenia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Blood loss anaemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Heparin-induced thrombocytopenia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Leukocytosis | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Neutrophilia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/6 (0%) | 1/33 (3%) | 3/32 (9.4%) | |||
| Bradycardia | 0/6 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||
| Cardiogenic shock | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Sinus bradycardia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Sinus tachycardia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Tachycardia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Gastrointestinal disorders | ||||||
| Constipation | 0/6 (0%) | 3/33 (9.1%) | 0/32 (0%) | |||
| Dysphagia | 0/6 (0%) | 0/33 (0%) | 3/32 (9.4%) | |||
| Abdominal pain upper | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Diarrhoea | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Haematochezia | 1/6 (16.7%) | 0/33 (0%) | 0/32 (0%) | |||
| Ileus | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Vomiting | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| General disorders | ||||||
| Pyrexia | 0/6 (0%) | 1/33 (3%) | 3/32 (9.4%) | |||
| Catheter site pain | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatic failure | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Infections and infestations | ||||||
| Septic shock | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pneumonia | 0/6 (0%) | 2/33 (6.1%) | 1/32 (3.1%) | |||
| Sepsis | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Cystitis | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Lice infestation | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Nosocomial infection | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Pneumonia staphylococcal | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Urinary tract infection | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Vulvovaginal mycotic infection | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Fall | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Tissue injury | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Vascular access complication | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Investigations | ||||||
| Blood lactate dehydrogenase increased | 0/6 (0%) | 1/33 (3%) | 2/32 (6.3%) | |||
| Blood bilirubin increased | 0/6 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||
| C-reactive protein increased | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Fibrin D dimer increased | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Serum ferritin increased | 0/6 (0%) | 0/33 (0%) | 2/32 (6.3%) | |||
| Anion gap increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Antibiotic level below therapeutic | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood creatine phosphokinase increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood creatinine increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Blood glucose increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood pH increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Blood phosphorus decreased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood sodium decreased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood sodium increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Blood triglycerides increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Blood urea increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Brain natriuretic peptide increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Drug trough level | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Electrocardiogram QT prolonged | 1/6 (16.7%) | 0/33 (0%) | 0/32 (0%) | |||
| Electrocardiogram ST segment elevation | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Eosinophil count increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Haematocrit decreased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Haemoglobin decreased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| International normalised ratio increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Monocyte count increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Neutrophil count increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Oxygen saturation decreased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Platelet count increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Procalcitonin increased | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Transaminases increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Troponin increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| White blood cell count increased | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypernatraemia | 0/6 (0%) | 0/33 (0%) | 2/32 (6.3%) | |||
| Metabolic acidosis | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Alkalosis | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Calcium deficiency | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Hypercalcaemia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Hyperkalaemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Hypertriglyceridaemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Hypoglycaemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Hyponatraemia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Metabolic alkalosis | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Nervous system disorders | ||||||
| Encephalopathy | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Presyncope | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Toxic encephalopathy | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/6 (0%) | 1/33 (3%) | 2/32 (6.3%) | |||
| Agitation | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Anxiety | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Hallucination, visual | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/6 (0%) | 2/33 (6.1%) | 1/32 (3.1%) | |||
| Renal failure | 0/6 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||
| Urinary retention | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Azotaemia | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Oliguria | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pneumothorax | 0/6 (0%) | 2/33 (6.1%) | 0/32 (0%) | |||
| Epistaxis | 1/6 (16.7%) | 1/33 (3%) | 0/32 (0%) | |||
| Pulmonary embolism | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Bronchial secretion retention | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Hypercapnia | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Pneumomediastinum | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Respiratory acidosis | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Respiratory disorder | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 1/6 (16.7%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Dermatitis diaper | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Rash maculo-papular | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Skin ulcer | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Subcutaneous emphysema | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Vascular disorders | ||||||
| Distributive shock | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Hypertension | 0/6 (0%) | 3/33 (9.1%) | 0/32 (0%) | |||
| Shock | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Deep vein thrombosis | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Hypotension | 0/6 (0%) | 1/33 (3%) | 1/32 (3.1%) | |||
| Phlebitis | 0/6 (0%) | 0/33 (0%) | 1/32 (3.1%) | |||
| Poor peripheral circulation | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
| Venous thrombosis | 0/6 (0%) | 1/33 (3%) | 0/32 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Apellis Clinical Trial Information Line |
|---|---|
| Organization | Apellis Pharmaceuticals, Inc |
| Phone | 1-833-284-6361 |
| clinicaltrials@apellis.com |
Responsible Party:
Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04402060
Other Study ID Numbers:
- APL9-COV-201
First Posted:
May 26, 2020
Last Update Posted:
Mar 23, 2022
Last Verified:
Mar 1, 2022