Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
The Phase 2 portion of the study will evaluate the efficacy and safety of 2 dose levels of
mavrilimumab relative to placebo (standard of care) in participants who have tested positive
for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with x-ray/computed
tomography (CT) evidence of bilateral pneumonia and active or recent signs of
hyperinflammation (fever or clinical laboratory results indicative of hyper-inflammation).
The Phase 3 portion is intended to confirm Phase 2 efficacy and safety findings. In both
Phase 2 and Phase 3, participants will be enrolled into 2 cohorts: Cohort 1 will include
non-intubated, hospitalized participants who require supplemental oxygen to maintain oxygen
saturation (SpO2) ≥ 92% (ie, "non-ventilated" participants); Cohort 2 will include
hospitalized participants for whom mechanical ventilation was recently initiated (ie,
"ventilated" participants). Following Screening, enrolled participants in each cohort will be
randomized 1:1:1 to receive one of 2 mavrilimumab dose levels, or placebo as a single
intravenous (IV) infusion (Day 1). Participants will undergo primary study assessments
through Day 29 and will be followed for safety through Day 90.
Drug: mavrilimumab
anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])
Other Name: (KPL-301; CAM3001)
Other: Placebo
matching placebo
Key Inclusion Criteria:
- Subject (or legally authorized representative) is able and willing to provide informed
consent, which includes compliance with study requirements and restrictions listed in
the consent form. Consent must be performed per institutional regulations.
- Age of ≥ 18 years
- Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization
- Hospitalized for SARS-CoV-2 (2019-nCoV)
- Bilateral pneumonia on chest x-ray or computed tomography
- Clinical laboratory results indicative of hyper-inflammation within 7 days prior to
randomization
- Cohort 1: Receiving any form of non-invasive ventilation OR oxygenation to maintain
SpO2 ≥ 92% and non-mechanically ventilated (examples include nasal cannula, face mask,
venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation)
- Cohort 2: Recently ventilated with mechanical ventilation beginning within 48 hours
prior to randomization
Key Exclusion Criteria:
- Onset of COVID-19 symptoms > 14 days prior to randomization
- Hospitalized > 7 days prior to randomization
- Need for invasive mechanical ventilation (Only for Cohort 1)
- Need for ECMO
- Serious prior or concomitant illness that in the opinion of the Investigator precludes
the subject from enrolling in the trial
- Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12
months, non-cell-depleting biological therapies (such as anti-tumor necrosis factor
[TNF], anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks
(or 5 half-lives, whichever is longer), treatment with alkylating agents within 12
weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate
mofetil (MMF), or other immunosuppressant (except for corticosteroids) within 4 weeks
prior to randomization. Medications that become standard of care for COVID-19 and/or
receive emergency use authorization may be allowed after discussion with the medical
monitor.
- If subject is receiving or has received hydroxychloroquine within 3 months prior to
screening visit, a corrected QT interval by Federicia method (QTcF) on Screening
electrocardiogram (ECG) ≥500ms is exclusionary. If subject has a pacemaker, this
criterion does not apply.
- Enrolled in another investigational study of a medical intervention within 30 days
prior to randomization. Participation in open label trials involving investigational
treatments for COVID-19 may be allowed upon approval by the Sponsor.
- Life expectancy less than 48 hours, in the opinion of the Investigator
- Known human immunodeficiency virus infection (regardless of immunological status),
known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus
positivity
UCLA Medical Center
Los Angeles, California, United States
SHARP Health Care
San Diego, California, United States
Affinity Health
Chicago, Illinois, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
Allina Health System
Minneapolis, Minnesota, United States
Mercy Clinic Hospitalists
Springfield, Missouri, United States
University of Cincinnati
Cincinnati, Ohio, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, United States
University of Texas Health Sciences
Houston, Texas, United States
Hospital Cardio Pulmonar
Salvador, Bahia, Brazil
Hospital Luxemburgo - Associação Mário Penna
Belo Horizonte, Minas Gerais, Brazil
CPCLIN - Centro de Pesquisas Clínicas
Natal, Rio Grande Do Norte, Brazil
Hospital Bruno Born
Lajeado, Rio Grande Do Sul, Brazil
UPECLIN - Unidade de Pesquisa Clínica
Botucatu, Sao Paulo, Brazil
IPECC - Instituto de Pesquisa Clínica de Campinas
Campinas, Sao Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, São Paulo, Brazil
Hospital Adventista de Belem
Belém, Brazil
IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará
Fortaleza, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
São José, Brazil
Hospital Alemão Oswaldo Cruz
São Paulo, Brazil
Clinica Las Condes
Santiago, Chile
Hospital Clinico Universidad de Chile
Santiago, Chile
Hospital Nacional Alberto Sabogal Sologuren
Bellavista, Peru
Essalud - Hospital de Emergencias Grau
Lima Cercado, Peru
Hospital Nacional Cayetano Heredia
San Martín De Porres, Peru
Clinica Providencia
San Miguel, Peru
University of Cape Town - Lung Institute
Cape Town, Western Cape, South Africa
IATROS International
Bloemfontein, South Africa
Tiervlei Trial Center
Cape Town, South Africa
TASK Eden
George, South Africa
Into Research - Little Company of Mary Medical Center
Pretoria, South Africa
Limpopo Clinical Research Initiative
Rustenburg, South Africa