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

Completed
COVID-19

Drug: Danicopan

Danicopan is a small molecule, orally administered complement factor D (FD) inhibitor

Other: Placebo

Danicopan matching placebo tablet

Drug: Remdesivir

Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.

Eligibility Criteria

Inclusion Criteria:

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. Illness of any duration and has laboratory-confirmed 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

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

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

7. Women of childbearing potential and men must agree to either abstinence or use at
least one acceptable method of contraception** from the time of screening through 30
days after the last dose of danicopan for women and 90 days after the last dose for
men.

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

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

1. Subjects with an eGFR 15-30 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 eGFR <15 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. Treatment with a complement inhibitor in the prior 8 weeks.*

8. Has active uncontrolled opportunistic infection, or uncontrolled cirrhosis.*

9. History of infection with N. meningitidis.*

10. Known history of hypersensitivity to danicopan or its excipients.*

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

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

13. History of liver cirrhosis.*

14. Previous participation in an ACTIV-5/BET trial.

15. Refuses to refrain from breastfeeding from the time of screening through 30 days after
the last dose of danicopan.*

16. Refuses to receive prophylactic antibiotics against meningococcal infections if the
subject has not been vaccinated in the 3 years prior to Study Day 1.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 99 Years
Countries
United States
Locations

University of Alabama at Birmingham School of Medicine - Infectious Disease
Birmingham, Alabama, United States

Kern Medical Center
Bakersfield, California, United States

UCSF Fresno Center for Medical Education and Research - Clinical Research Center
Fresno, California, United States

University of California Los Angeles Medical Center - Westwood Clinic
Los Angeles, California, United States

Hoag Hospital Newport Beach
Newport Beach, California, United States

Penrose Hospital - Emergency Medicine
Colorado Springs, Colorado, United States

St. Francis Medical Center
Colorado Springs, Colorado, United States

St. Anthony Hospital
Lakewood, Colorado, United States

St. Anthony Hospital North Health Campus
Westminster, Colorado, United States

Nuvance Health Danbury Hospital - Infectious Disease
Danbury, Connecticut, United States

Yale School of Medicine - The Anlyan Center for Medical Research & Education - Immunobiology
New Haven, Connecticut, United States

Nuvance Health - Norwalk Hospital - Asthma Pulmonary and Critical Care Medicine
Norwalk, Connecticut, United States

University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
Gainesville, Florida, United States

Mayo Clinic Florida
Jacksonville, Florida, United States

Great Lakes Clinical Trials
Chicago, Illinois, United States

Carle Foundation Hospital
Urbana, Illinois, United States

Northwestern Medicine - Central DuPage Hospital - Infectious Disease
Winfield, Illinois, United States

Norton Healthcare
Louisville, Kentucky, United States

University of Louisville - Division of Infectious Diseases
Louisville, Kentucky, United States

Brigham and Women's Hospital - Infectious Diseases
Boston, Massachusetts, United States

William Beaumont Hospital - Royal Oak Campus - Infectious Disease
Royal Oak, Michigan, United States

Hennepin Healthcare Research Institute
Minneapolis, Minnesota, United States

Mayo Clinic, Rochester - Infectious Diseases
Rochester, Minnesota, United States

University of Nebraska Medical Center - Infectious Diseases
Omaha, Nebraska, United States

Jacobi Medical Center
Bronx, New York, United States

Montefiore Medical Center - Infectious Diseases
Bronx, New York, United States

The State University of New York - University at Buffalo - Department of Medicine
Buffalo, New York, United States

Mount Sinai School of Medicine - Medicine - Infectious Diseases
New York, New York, United States

Nuvance Health - Vassar Brothers Medical Center
Poughkeepsie, New York, United States

Stony Brook Medicine - Stony Brook University Hospita
Stony Brook, New York, United States

Wake Forest Baptist Health - Infectious Diseases
Winston-Salem, North Carolina, United States

St. Charles Health System - St. Charles Bend Hospital
Bend, Oregon, United States

Doylestown Hospital
Doylestown, Pennsylvania, United States

Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
Hershey, Pennsylvania, United States

Kent County Memorial Hospital
Warwick, Rhode Island, United States

Hendrick Health - Hendrick Medical Center
Abilene, Texas, United States

Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
Dallas, Texas, United States

University of Utah - Infectious Diseases
Salt Lake City, Utah, United States

West Virginia University - Infectious Diseases Clinic
Morgantown, West Virginia, United States

National Institute of Allergy and Infectious Diseases (NIAID)
NCT Number
Keywords
Adults
Covid-19
Multicenter
Putative
Therapeutics
MeSH Terms
COVID-19
Remdesivir