ACTIV-5 / Big Effect Trial (BET-B) for the Treatment of COVID-19
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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. Subjects will be assessed daily while hospitalized. Once subjects
      are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60
      as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or
      collection of samples and may be conducted by phone. All subjects will undergo a series of
      efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and
      plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to
      study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs
      (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal
      or nasal swabs may be substituted) and blood research samples plus safety laboratory tests
      will be collected on Day 15 and 29 if the subject attends an in-person visit or is still
      hospitalized. However, if infection control considerations or other restrictions prevent the
      subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only
      clinical data will be obtained.

      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. The key secondary objectives are to 1)
      evaluate the clinical efficacy of different investigational therapeutics as assessed by time
      to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive
      and without respiratory failure through Day 29.

      Contacts:

      20-0013 Central Contact

      Telephone: 1 (301) 7617948

      Email: DMIDClinicalTrials@niaid.nih.gov
    

Intervention name(s): Lenzilumab; Placebo; Remdesivir
Intervention type(s): Biological; Other; Drug
Intervention description(s): Lenzilumab is a first-in-class recombinant monoclonal antibody targeting soluble human GM-CSF, with potential immunomodulating activity, high binding affinity in the pM range, and 94% specificity to the human germline, which reduces immunogenicity.; Placebo for lenzilumab is commercially sourced 0.9% sodium chloride.; Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Intervention MeSH terms: Remdesivir; Lenzilumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Adults; COVID-19; Multicenter; Putative; Therapeutics