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. There will be interim monitoring to introduce new arms and 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. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
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. There will be interim monitoring to introduce new arms and 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. Because background standards
of supportive care may evolve/improve over time as more is learned about successful
management of COVID-19, comparisons of safety and efficacy will be based on data from
concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will
actively monitor interim data to make recommendations about early study closure or changes to
study arms.
The initial sample size is projected to be 572 subjects to achieve 400 subjects with a
"recovered" status (per the primary objective). The primary analysis will be based on those
subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity
subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or
"Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also
of public health importance. Hence, enrollment will be permitted until the date of April 20,
2020 to ensure 400 recoveries and provide additional data about this important subgroup. With
recent enrollment rates, the total sample size may be 600 to over 800.
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 as an outpatient. For
discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain
safety laboratory tests and 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, Day 15 and 29 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 may also be 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. As little is known
about the clinical course of COVID-19, a pilot study will be used for a blinded sample size
reassessment.
Contacts:
20-0006 Central Contact
Telephone: 1 (301) 7617948
Other: Placebo
The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.
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 infection.
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 specimen, as
documented by either or the following:
1. PCR positive in sample collected < 72 hours prior to randomization; OR
Exclusion Criteria:
2. PCR positive in sample collected >/= 72 hours prior to randomization, documented
inability to obtain a repeat sample (e.g. due to lack of testing supplies,
limited testing capacity, results taking >24 hours, etc.) AND progressive disease
suggestive of ongoing SARS-CoV-2 infection.
6. Illness of any duration, and at least one of the following:
1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
2. SpO2 < / = 94% on room air, OR
3. Requiring supplemental oxygen, OR
4. Requiring mechanical ventilation.
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 for the treatment of COVID-19 or
SARS-CoV-2 through Day 29.
Exclusion Criteria:
1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit
of normal.
2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving
hemodialysis or hemofiltration).
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.
5. Allergy to any study medication.
University of Alabama at Birmingham School of Medicine - Infectious Disease
Birmingham, Alabama, 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
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 Human Immunodeficiency Virus, Infectious Disease, and Global Medicine
San Francisco, California, United States
Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
Stanford, California, United States
Cedars Sinai Medical Center
West Hollywood, California, United States
Denver Health Division of Hospital Medicine - Main Campus
Denver, Colorado, United States
Emory Vaccine Center - The Hope Clinic
Decatur, Georgia, United States
Northwestern Hospital - Infectious Disease
Chicago, Illinois, United States
University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
Chicago, Illinois, 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
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
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
Vanderbilt University Medical Center - Infectious Diseases
Nashville, Tennessee, 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
University of Texas Health Science Center at San Antonio - Infectious Diseases
San Antonio, Texas, 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
The University of Washington - Virology Research Clinic
Seattle, Washington, United States
Providence Sacred Heart Medical Center
Spokane, Washington, United States
Madigan Army Medical Center - Infectious Disease Clinic
Tacoma, Washington, United States
University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases
Copenhagen, Denmark
Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik
Bonn, Nordrhein-Westfalen, Germany
Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I
Cologne, Germany
Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie
Frankfurt, Germany
AHEPA University Hospital - 1st Department of Internal Medicine
Thessaloniki, Central Macedonia, Greece
Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services
Athens, Greece
National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center
Tokyo, Japan
Seoul National University Bundang Hospital - Division of Infectious Diseases
Bundang-gu Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
Seoul, Jongno-gu, Korea, Republic of
Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
Mexico City, Mexico
Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
Mexico City, Mexico
National Centre for Infectious Diseases
Singapore, Singapore
Hospital Clinic Barcelona, Servicio de Salud Internacional
Barcelona, Cataluña, Spain
Hospital Germans Trias i Pujol - Servei Malalties Infeccioses
Barcelona, Cataluña, Spain
Royal Sussex County Hospital - Department of Intensive Care Medicine
East Sussex, Brighton, United Kingdom
Saint Thomas' Hospital - Directorate of Infection
London, London, City Of, United Kingdom
Royal Victoria Infirmary - Department of Infectious Diseases
Level 6, Ward 19, Newcastle Upon Tyne, United Kingdom
St. James's University Hospital - Infectious Diseases
Leeds, West Yorkshire, United Kingdom
John Radcliffe Hospital
Headington, Oxford, United Kingdom