Phase 2
N=72
A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19
COVID · Covid-19 · Coronavirus · Coronavirus Infection · Severe Acute Respiratory Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT04402060 ↗Enrolled (actual)
72
Serious AEs
42.3%
Results posted
Mar 2022
Primary outcome: Primary: Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs — 4; 23; 22; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- APL-9 (Drug); Vehicle Control (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Apellis Pharmaceuticals, Inc.
- Primary completion
- Feb 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs |
4; 23; 22; 1; 14; 15 | — |
| SECONDARY Hospital Length of Stay |
21.5; 15.5 | 0.82 |
| SECONDARY Overall Survival |
NA; NA | 0.36 |
| SECONDARY Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time |
0.4; 1.2; 0.6; 0.6; 1.8; 0.9 | — |
| SECONDARY Total Duration of Mechanical Ventilation |
47.0; 8.5 | 0.03 sig |
| SECONDARY Total Duration of Oxygen Therapy |
9.0; 8.0 | 0.93 |
| SECONDARY Serum Concentration of APL-9 Over Time |
0.0; 3.9; 0.0; 48.1; 77.7; 2.6 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 |
38.0; 91.4; 2.1; 2.0; -3.9; 0.2 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) |
-69.6; -357.6; -4.0; -337.7; -1560.8; -87.0 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb |
-0.6; -0.9; -0.1 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50) |
-157.7; -84.3; -2.3 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes |
10325.4; 23929.1 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes |
0.0 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase |
-464.6; -135.2; -106.1 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin |
-783.8; 217.2; 907.9; -133.6; -53.1; -19.3 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen |
-5435.4; -4554.0; -147.3; 3995.1; -1348.2 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP) |
-7.0; 6.4; -3.1 | — |
| SECONDARY Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6) |
19.6; 10.4; -0.6; -8.1; 203.6; 71.3 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04402060). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.