Adaptive COVID-19 Treatment Trial 4 (ACTT-4)
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

Summary: 
      ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone
      and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are
      discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For
      discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain
      safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary
      research as well as clinical outcome data. However, if infection control or other
      restrictions limit the ability of the subject to return to the clinic, these visits may be
      conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have
      laboratory tests or collection of samples and is conducted by phone. The primary objective is
      to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone +
      remdesivir as assessed by the mechanical ventilation free survival by Day 29.
    

Detailed description: 
      This study is an adaptive randomized double-blind placebo-controlled trial to evaluate the
      safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with
      COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100
      sites globally. The study will compare different investigational therapeutic agents to a
      control arm. New arms can be introduced according to scientific and public health needs.
      There will be interim monitoring to allow early stopping for futility, efficacy, or safety.
      If one therapy proves to be efficacious, then this treatment may become the control arm for
      comparison(s) with new experimental treatment(s). Any such change would be accompanied by an
      updated sample size. This adaptive platform is used to rapidly evaluate different
      therapeutics in a population of those hospitalized with moderate to severe COVID-19. The
      platform will provide a common framework sharing a similar population, design, endpoints, and
      safety oversight. New stages with new therapeutics can be introduced. One independent Data
      and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make
      recommendations about early study closure or changes to study arms.

      ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone
      and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are
      discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For
      discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain
      safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary
      research as well as clinical outcome data. However, if infection control or other
      restrictions limit the ability of the subject to return to the clinic, these visits may be
      conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have
      laboratory tests or collection of samples and is conducted by phone.

      All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety
      laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs
      will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized).
      OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and
      29 (if the subject attends an in-person visit or are still hospitalized).

      The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus
      dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29.
      The key secondary objective is to evaluate the clinical efficacy of baricitinib + remdesivir
      versus dexamethasone + remdesivir according to clinical status (8-point ordinal scale) at Day
      15.

      Contacts:

      20-0006 Central Contact

      Telephone: 1 (301) 7617948

      Email: DMIDClinicalTrials@niaid.nih.gov
    

Intervention name(s): Baricitinib; Dexamethasone; Placebo; Remdesivir
Intervention type(s): Drug; Drug; Other; Drug
Intervention description(s): Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name [1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile. Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.; Dexamethasone Sodium Phosphate Injection, USP, is an adrenocortical steroid anti-inflammatory drug. It is a water-soluble inorganic ester of dexamethasone. Each mL contains dexamethasone sodium phosphate equivalent to dexamethasone phosphate 4 mg or dexamethasone 3.33 mg; benzyl alcohol 10 mg added as preservative; sodium citrate dihydrate 11 mg; sodium sulfite 1 mg as an antioxidant.; Placebo matching oral baricitinib or intravenous dexamethasone.; Drug remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Intervention MeSH terms: Remdesivir; Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: ACTT; Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety