ACTIV-5 / Big Effect Trial (BET-B) for the Treatment of COVID-19

Completed · Phase 2 · Has a placebo group

Conditions studied: COVID-19

In brief

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

Key facts

Study ID

NCT04583969

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

527

Starts

2020-10-23

Expected to finish

2022-04-22

Last updated by the study team

2023-06-05

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
• Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
• Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
• Male or non-pregnant female adult >/= 18 years of age at time of enrollment.
• Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) in any respiratory specimen, or saliva </=14 days prior to randomization.
• Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).
• Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception* from the time of screening through 5 months post study intraperitoneal (IP) dosing.
• Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.
• Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.

You may not qualify if…

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal.
• Subjects with a low glomerular filtration rate (eGFR), specifically:
• Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
• All subjects with a glomerular filtration rate (eGFR) <20 mL/min (including hemodialysis and hemofiltration) are excluded.
• Pregnancy or breast feeding.
• Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
• Allergy to any study medication.
• Received five or more doses of remdesivir prior to screening.
• Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
• Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 [e.g., anakinra, canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
• Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
• Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
• Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
• Received any live vaccine in the 4 weeks prior to screening.
• Known active tuberculosis.
• Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
• History of pulmonary alveolar proteinosis (PAP).
• Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
• Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
• Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
• Previous participation in an ACTIV-5/Big Effect Trial (BET).

Where it is running

• The University of Arizona - Banner University Medical Center Tucson Campus - Tucson — Tucson, Arizona, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Kern Medical Center — Bakersfield, California, United States
• UCSF Fresno Center for Medical Education and Research - Clinical Research Center — Fresno, California, United States
• University of Southern California - Infectious Diseases — Los Angeles, California, United States
• Hoag Hospital Newport Beach — Newport Beach, California, United States
• Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases — Stanford, California, United States
• Penrose Hospital - Emergency Medicine — Colorado Springs, Colorado, United States
• St. Francis Medical Center — Colorado Springs, Colorado, United States
• St. Anthony Hospital — Lakewood, Colorado, United States
• St. Anthony Hospital North Health Campus — Westminster, Colorado, United States
• Nuvance Health Danbury Hospital - Infectious Disease — Danbury, Connecticut, United States
• Yale School of Medicine - The Anlyan Center for Medical Research & Education - Immunobiology — New Haven, Connecticut, United States
• Nuvance Health - Norwalk Hospital - Asthma Pulmonary and Critical Care Medicine — Norwalk, Connecticut, United States
• University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine — Gainesville, Florida, United States
• Mayo Clinic Florida — Jacksonville, Florida, United States
• Grady Memorial Hospital — Atlanta, Georgia, United States
• The Hope Clinic of Emory University — Decatur, Georgia, United States
• Cook County Health and Hospitals System - Ruth M Rothstein CORE Center — Chicago, Illinois, United States
• Rush University Medical Center — Chicago, Illinois, United States
• Great Lakes Clinical Trials — Chicago, Illinois, United States
• Carle Foundation Hospital — Urbana, Illinois, United States
• Northwestern Medicine - Central DuPage Hospital - Infectious Disease — Winfield, Illinois, United States
• Norton Healthcare — Louisville, Kentucky, United States
• University of Alabama at Birmingham School of Medicine - Infectious Disease — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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