ACTT-3 will evaluate the combination of interferon beta-1a 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.
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-3 will evaluate the combination of interferon beta-1a 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 for patients with baseline ordinal score 4,
5 and 6. 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
Drug: Interferon beta-1a
Rebif (R) is a purified 166 amino acid human interferon beta glycoprotein with an amino acid sequence identical to natural fibroblast derived human interferon beta. Each 0.5 mL prefilled syringe contains 44 mcg of interferon beta-1a, 4 mg human albumin, USP; 27.3 mg mannitol, USP; 0.4 mg sodium acetate; and water for injection, USP.
Other: Placebo
The interferon beta-1a placebo contains either 0.5 mL 0.9% normal saline or 0.5 mL sterile water for injection.
Drug: Remdesivir
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.
Inclusion Criteria:
1. Admitted to a hospital with symptoms suggestive of COVID-19.
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 polymerase chain
reaction (PCR) or other commercial or public health assay in any respiratory specimen
or saliva, as documented by either of the following:
- PCR or other assay positive in sample collected < 72 hours prior to
randomization; OR
- PCR or other assay positive in sample collected >/= 72 hours but < 7 days prior
to randomization AND progressive disease suggestive of ongoing SARS-CoV-2
infection.
Note: if written documentation of the positive test result is not available at
enrollment (e.g., report from other institution), the subject may be enrolled but the
PCR should be repeated at the time of enrollment.
6. Illness of any duration, and at least one of the following:
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- SpO2 < / = 94% on room air, OR
- Requiring supplemental oxygen.
7. Women of childbearing potential must agree to either abstinence or use at least one
primary form of contraception not including hormonal contraception from the time of
screening through Day 29.
8. Agrees to not participate in another clinical trial (both pharmacologic and other
types of interventions) for the treatment of COVID-19 through Day 29.
Exclusion Criteria:
1. Anticipated discharge from the hospital or transfer to another hospital which is not a
study site within 72 hours.
2. Subject meets criteria for ordinal scale category 6 or 7 at the time of screening.
3. Subject has a positive test for influenza virus during this current hospital
admission.
4. Subjects with an estimated glomerular filtration rate (eGFR) < 30 mL/min are excluded
unless in the opinion of the PI, the potential benefit of receiving remdesivir
outweighs the potential risk of study participation.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper
limits of normal.
6. Total white cell blood cell count (WBC) <1500 cells/microliter.
7. Platelet count <50,000/microliter.
8. History of chronic liver disease (e.g., jaundice, ascites, hepatic encephalopathy,
history of bleeding esophageal or gastric varices). No laboratory testing is needed.
9. Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day
1 until three weeks after the last study product is given are not excluded).
10. Allergy to any study medication including history of hypersensitivity to natural or
recombinant interferon beta or human albumin.
11. Patient has a chronic or acute medical condition or is taking a medication that cannot
be discontinued at enrollment, that in the judgement of the PI, places them at
unacceptable risk for a poor clinical outcome if they were to participate in the
study.
12. Received three or more doses of remdesivir, including the loading dose, outside of the
study for COVID-19.
13. Received convalescent plasma or intravenous immunoglobulin [IVIg] for the treatment of
COVID-19.
14. Received any interferon product within two weeks of screening, either for the
treatment of COVID-19 or for a chronic medical condition (e.g., multiple sclerosis,
HCV infection).
15. Received any of the following in the two weeks prior to screening as treatment of
COVID-19:
- Small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatinib, gefitinib,
acalabrutinib, etc.);
- Monoclonal antibodies targeting cytokines (e.g., TNF inhibitors,
anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.);
- Monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19.
16. Prior enrollment in ACTT-3.
University of Alabama at Birmingham School of Medicine - Infectious Disease
Birmingham, Alabama, United States
UCSF Fresno Center for Medical Education and Research - Clinical Research Center
Fresno, California, United States
University of California San Diego Health - Jacobs Medical Center
La Jolla, California, United States
University of California Los Angeles Medical Center - Westwood Clinic
Los Angeles, California, United States
University of California Irvine Medical Center - Infectious Disease
Orange, California, United States
VA Palo Alto Health Care System - Infectious Diseases
Palo Alto, California, United States
Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
Palo Alto, California, United States
University of California Davis Medical Center - Internal Medicine - Infectious Disease
Sacramento, California, United States
Naval Medical Center San Diego - Infectious Disease Clinic
San Diego, California, United States
University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of HIV, ID, and Global Medicine
San Francisco, California, United States
Cedars Sinai Medical Center
West Hollywood, California, United States
Eastern Colorado Health Care System
Aurora, Colorado, United States
Denver Health Division of Hospital Medicine - Main Campus
Denver, Colorado, United States
University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
Gainesville, Florida, United States
University of Florida Health - Jacksonville - Department of Emergency Medicine
Jacksonville, Florida, United States
University of Miami Miller School of Medicine - Infectious Diseases
Miami, Florida, United States
Emory Vaccine Center - The Hope Clinic
Decatur, Georgia, United States
Atlanta VA Medical Center - Infectious Diseases Clinic
Decatur, Georgia, United States
Tripler Army Medical Center (TAMC)
Honolulu, Hawaii, United States
Northwestern Hospital - Infectious Disease
Chicago, Illinois, United States
University of Illinois at Chicago Division of Infectious Diseases
Chicago, Illinois, United States
University of Iowa Hospitals & Clinics - Department of Internal Medicine
Iowa City, Iowa, United States
Ochsner Medical Center - Kenner - Department of Infectious Diseases
Kenner, Louisiana, United States
Southeast Louisiana Veterans Health Care System - Section of Infectious Diseases
New Orleans, Louisiana, United States
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
Baltimore, Maryland, United States
Johns Hopkins Hospital - Medicine - Infectious Diseases
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section
Bethesda, Maryland, United States
Massachusetts General Hospital - Infectious Diseases
Boston, Massachusetts, United States
University of Massachusetts Medical School - Infectious Diseases and Immunology
Worcester, Massachusetts, United States
University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
Minneapolis, Minnesota, United States
Saint Louis University - Center for Vaccine Development
Saint Louis, Missouri, United States
University of Nebraska Medical Center - Infectious Diseases
Omaha, Nebraska, United States
University of New Mexico Clinical and Translational Science Center
Albuquerque, New Mexico, United States
Montefiore Medical Center - Infectious Diseases
Bronx, New York, United States
New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology
New York, New York, United States
University of Rochester Medical Center - Vaccine Research Unit
Rochester, New York, United States
Duke Human Vaccine Institute - Duke Vaccine and Trials Unit
Durham, North Carolina, United States
Womack Army Medical Center - Pulmonary and Respiratory Services
Fort Bragg, North Carolina, United States
Kaiser Permanente Northwest - Center for Health Research
Portland, Oregon, United States
Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
Hershey, Pennsylvania, United States
Hospital of the University of Pennsylvania - Infectious Diseases
Philadelphia, Pennsylvania, United States
Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
Dallas, Texas, United States
University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases
Dallas, Texas, United States
Brooke Army Medical Center
Fort Sam Houston, Texas, United States
University of Texas Medical Branch - Division of Infectious Disease
Galveston, Texas, United States
Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas, United States
Methodist Hospital - Houston
Houston, Texas, United States
University of Texas Health Science Center at San Antonio - Infectious Diseases
San Antonio, Texas, United States
University of Utah - Infectious Diseases
Salt Lake City, Utah, United States
University of Virginia - Acute Care Surgery
Charlottesville, Virginia, United States
Naval Medical Center Portsmouth - Infectious Disease Division
Portsmouth, Virginia, United States
EvergreenHealth Infectious Disease Service
Kirkland, Washington, United States
Providence Sacred Heart Medical Center
Spokane, Washington, United States
Madigan Army Medical Center - Infectious Disease Clinic
Tacoma, Washington, United States
National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center
Tokyo, Japan
Seoul National University Bundang Hospital - Division of Infectious Diseases
Seongnam, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
Seoul, Jongno-gu, Korea, Republic of
Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
Mexico City, Mexico
Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
Mexico City, Mexico
National University Health System - Division of Infectious Diseases
Singapore, Singapore
National Centre for Infectious Diseases (NCID)
Singapore, Singapore
Changi General Hospital - Clinical Trials and Research Unit (CTRU)
Singapore, Singapore
Ng Teng Fong General Hospital - Infectious Disease Service
Singapore, Singapore