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


Trial ID: NCT04583956


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-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab 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.

Official Title

A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

Stanford Investigator(s)

Nidhi Rohatgi, MD MS
Nidhi Rohatgi, MD MS

Clinical Professor, Medicine Clinical Professor (By courtesy), Neurosurgery


Inclusion Criteria:

   1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19)
   and requires ongoing medical care.

   2. Subject (or legally authorized representative) provides informed consent prior to
   initiation of any study procedures.

   3. Subject (or legally authorized representative) understands and agrees to comply with
   planned study procedures.

   4. Male or non-pregnant female adult >/= 18 years of age at time of enrollment.

   5. 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    randomization.

   6. Illness of any duration, and requiring, just prior to randomization, supplemental
   oxygen (any flow), mechanical ventilation or ECMO (ordinal score 5, 6, or 7).

   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 IP dosing.

   Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with
   spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive
   pills, and surgical sterilization.

   8. 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.

Exclusion Criteria:

   1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper
   limit of normal.

   2. Subjects with a low glomerular filtration rate (eGFR), specifically:

      1. Subjects with an 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.

      2. All subjects with an a glomerular filtration rate (eGFR) <20 mL/min (including
      hemodialysis and hemofiltration) are excluded.

   3. Pregnancy or breast feeding.

   4. Anticipated discharge from the hospital or transfer to another hospital which is not a
   study site within 72 hours of enrollment.

   5. Allergy to any study medication.

   6. Received five or more doses of remdesivir prior to screening.

   7. Received two or more doses of > 60 mg of prednisone or equivalent in the 7 days prior
   to screening.

   8. 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.

   9. 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

10. 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.

11. Received Granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g.,
   sargramostim) within 2 months prior to screening.

12. Received other immunosuppressants in the 4 weeks prior to screening and in the
   judgment of the investigator, the risk of immunosuppression with risankizumab is
   larger than the risk of Coronavirus Disease 2019 (COVID-19).

13. Received any live vaccine in the 4 weeks prior to screening.

14. Known active tuberculosis.

15. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated
   hepatitis C (HCV) infection.

16. History of pulmonary alveolar proteinosis (PAP).

17. Has a malignancy and currently receiving immunosuppressive chemotherapy,
   immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.

18. Has a medical condition that could, in the judgment of the investigator, limit the
   interpretation and generalizability of trial results.

19. Positive test for influenza virus during the current illness (influenza testing is not
   required by protocol).

20. Previous participation in an ACTIV-5/Big Effect Trial (BET)


other: Placebo

drug: Remdesivir

biological: Risankizumab


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305