Summary

Eligibility
for people ages 18-99 (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

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 40 sites throughout the US. 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

Details

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 40 sites throughout the US. 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. 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 1) to 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

Keywords

COVID-19 Adults Multicenter Platform Putative Therapeutics Remdesivir Risankizumab Remdesivir + Risankizumab

Eligibility

You can join if…

Open to people ages 18-99

  1. Admitted to a hospital with symptoms suggestive of 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. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen, as documented by either of the following:
  6. PCR positive in sample collected < 72 hours prior to screening; OR
  7. PCR positive in sample collected >/= 72 hours but < 14 days prior to screening AND non-improving or progressive disease suggestive of ongoing SARS-CoV-2 infection.

Note: if written documentation of the positive test result is not available at the time of enrollment (e.g., report came from other institution), the subject may be enrolled but the PCR should be repeated at the time of enrollment.

  1. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or ECMO (ordinal scale category 5, 6, or 7).
  2. 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.

  1. 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.

You CAN'T join if...

  1. ALT or AST > 5 times the upper limit of normal.
  2. Subjects with a low glomerular filtration rate (eGFR), specifically:
  3. Subjects with an eGFR 20-30 mL/min are excluded unless in the opinion of the PI, the potential benefit of participation outweighs the potential risk of study participation.
  4. All subjects with an eGFR <20 mL/min (including hemodialysis and hemofiltration) are excluded.
  5. Pregnancy or breast feeding.
  6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
  7. Allergy to any study medication.
  8. Received five or more doses of remdesivir prior to screening.
  9. Received two or more doses of > 60 mg of prednisone or equivalent in the 7 days prior to screening
  10. 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.
  11. 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 screening.
  12. . 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.
  13. . Received Granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
  14. . 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 COVID-19.
  15. . Received any live vaccine in the 4 weeks prior to screening.
  16. . Known active tuberculosis.
  17. . Known history of HIV, Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
  18. . History of pulmonary alveolar proteinosis (PAP).
  19. . Has active malignancy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
  20. . Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
  21. . Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
  22. . Previous participation in an ACTIV-5/BET trial.

Locations

  • UCSF Fresno Center for Medical Education and Research - Clinical Research Center not yet accepting patients
    Fresno California 93721 United States
  • Hoag Hospital Newport Beach accepting new patients
    Newport Beach California 92663 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT04583956
Phase
Phase 2
Study Type
Interventional
Last Updated