Clinical trial NCT04402060: A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID
Covid-19
Coronavirus
Coronavirus Infection
Severe Acute Respiratory Syndrome
Severe Acute Respiratory Syndrome Coronavirus 2
Sars-CoV2
Ards
Acute Respiratory Distress Syndrome
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-26
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
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
Secondary outcomes:
measure: Hospital Length of Stay
timeFrame: Part 2: Day 1 up to Day 58
measure: Overall Survival
timeFrame: Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days])
measure: Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time
timeFrame: Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21)
measure: Total Duration of Mechanical Ventilation
timeFrame: Part 2: Day 1 up to Day 58
measure: Total Duration of Oxygen Therapy
timeFrame: Part 2: Day 1 up to Day 58
measure: Serum Concentration of APL-9 Over Time
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)
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4
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)
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC)
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)
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb
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)
measure: Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50)
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP)
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
measure: 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)
timeFrame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21)
Other outcomes:
Locations:
city: Fresno
country: United States
facility: University of California at San Francisco - Fresno
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Jacksonville Beach
country: United States
facility: Baptist Medical Center Beaches
state: Florida
city: Miami
country: United States
facility: Westchester General Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern University, Feinberg School of Medicine
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Lutheran Health Physicians
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Women's and Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: Norton Audobon Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Cambridge Medical Trials
state: Louisiana
city: Southfield
country: United States
facility: Ascension Providence Hospital
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers University - Robert Wood Johnson Medical School
state: New Jersey
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Temple
country: United States
facility: Texas A&M College of Medicine - Scott and White
state: Texas
city: Campina Grande Do Sul
country: Brazil
facility: Hospital Angelina Caron
state: Paraná
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: Santo André
country: Brazil
facility: Hospital Estadual Mario Covas
state: Sao Paulo
city: São Bernardo Do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clinicos LTDA EPP
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: Sao Paulo
city: Botucatu
country: Brazil
facility: UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - FMB/UNESP
state: São Paulo
Study officials:
References: