Adaptive COVID-19 Treatment Trial 2 (ACTT-2)
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

Summary: 
      ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir
      alone. 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 and oropharyngeal (OP) swab and blood (serum only) samples for secondary
      research as well as clinical outcome data. However, infection control or other restrictions
      may limit the ability of the subject to return to the clinic. In this case, 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 outcome
      is time to recovery 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-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir
      alone. 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 and oropharyngeal (OP) swab and blood (serum only) samples for secondary
      research as well as clinical outcome data. However, infection control or other restrictions
      may limit the ability of the subject to return to the clinic. In this case, 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 outcome is time to recovery by Day 29. A key secondary outcome evaluates
      treatment-related improvements in the 8-point ordinal scale at Day 15. Each stage may
      prioritize different secondary endpoints for the purpose of multiple comparison analyses.

      Contacts:

      20-0006 Central Contact

      Telephone: 1 (301) 7617948

      Email: DMIDClinicalTrials@niaid.nih.gov
    

Intervention name(s): Placebo; Remdesivir; Baricitinib
Intervention type(s): Other; Drug; Drug
Intervention description(s): The matching Baricitinib placebo contains lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The coating for the placebo tablet is identical to that of the corresponding active tablet.; 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.; 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.
Intervention MeSH terms: Remdesivir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety