ACTIV-5 / Big Effect Trial (BET-C) 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 COVID-19.
      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-C stage will evaluate the combination of remdesivir with danicopan vs remdesivir with
      a 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, plasma and RNA)
      research samples on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11
      while hospitalized. 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 danicopan 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 COVID-19.
      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-C stage will evaluate the combination of remdesivir with danicopan vs remdesivir with
      a 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, plasma and RNA)
      research samples on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11
      while hospitalized. 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 danicopan 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 1) to evaluate the clinical
      efficacy of danicopan as assessed by time to recovery compared to the control arm 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): Danicopan; Placebo; Remdesivir
Intervention type(s): Drug; Other; Drug
Intervention description(s): Danicopan is a small molecule, orally administered complement factor D (FD) inhibitor; Danicopan matching placebo tablet; Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Intervention MeSH terms: Remdesivir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Adults; covid-19; Multicenter; Putative; Therapeutics