Adaptive COVID-19 Treatment Trial 2 (ACTT-2)
COVID-19
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Adaptive, COVID-19, Efficacy, Multicenter, novel coronavirus, Safety
Eligibility Criteria
Inclusion Criteria:
- Admitted to a hospital with symptoms suggestive of COVID-19.
- Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
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 of the following:
- PCR positive in sample collected < 72 hours prior to randomization; OR
- 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.
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, OR
- Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
- 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.
- Agrees to not participate in another clinical trial for the treatment of COVID-19 through Day 29.
Exclusion Criteria:
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
- Estimated glomerular filtration rate (eGFR) < 30 ml/min or patient is receiving hemodialysis or hemofiltration at time of screening.
- Neutropenia (absolute neutrophil count <1000 cells/microliter) (<1.0 x 103/microliter or <1.0 GI/L).
- Lymphopenia (absolute lymphocyte count <200 cells/microliter) (<0.20 x 103/microliter or <0.20 GI/L)
- Pregnancy or breast feeding.
- Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
- Allergy to any study medication.
- Received three or more doses of remdesivir, including the loading dose, outside of the study under the EUA (or similar mechanism) for COVID-19.
- Received convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19, the current illness for which they are being enrolled.
- Received small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatibib, genfinitib), in the 1 week prior to screening
- Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
- Received monoclonal antibodies targeting B-cell (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
- Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with baricitinib is larger than the risk of COVID-19.
- Received >/= 20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to screening.
- Use of probenecid that cannot be discontinued at study enrollment.
- Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
- Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
- Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
- Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).
- Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.
Sites / Locations
- University of Alabama at Birmingham School of Medicine - Infectious Disease
- University of California San Diego Health - Jacobs Medical Center
- University of California Los Angeles Medical Center - Westwood Clinic
- University of California Irvine Medical Center - Infectious Disease
- VA Palo Alto Health Care System - Infectious Diseases
- Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
- University of California Davis Medical Center - Internal Medicine - Infectious Disease
- Naval Medical Center San Diego - Infectious Disease Clinic
- University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine
- Cedars Sinai Medical Center
- Eastern Colorado Health Care System
- Denver Health Division of Hospital Medicine - Main Campus
- Georgetown University Medical Center - Division of Infectious Diseases
- University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
- University of Miami Miller School of Medicine - Infectious Diseases
- Emory Vaccine Center - The Hope Clinic
- Atlanta VA Medical Center - Infectious Diseases Clinic
- Northwestern Hospital - Infectious Disease
- University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
- Indiana University School of Medicine - Infectious Diseases
- Ochsner Medical Center - Kenner - Department of Infectious Diseases
- Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases
- University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
- Johns Hopkins Hospital - Medicine - Infectious Diseases
- Walter Reed National Military Medical Center
- National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section
- Massachusetts General Hospital - Infectious Diseases
- University of Massachusetts Medical School - Infectious Diseases and Immunology
- University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
- Saint Louis University - Center for Vaccine Development
- University of Nebraska Medical Center - Infectious Diseases
- University of New Mexico Clinical and Translational Science Center
- Montefiore Medical Center - Infectious Diseases
- New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology
- University of Rochester Medical Center - Vaccine Research Unit
- Duke Human Vaccine Institute - Duke Vaccine and Trials Unit
- Womack Army Medical Center - Pulmonary and Respiratory Services
- Kaiser Permanente Northwest - Center for Health Research
- Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
- University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology
- Vanderbilt University Medical Center - Infectious Diseases
- Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
- University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases
- Brooke Army Medical Center
- University of Texas Medical Branch - Division of Infectious Disease
- Baylor College of Medicine - Molecular Virology and Microbiology
- University of Texas Health Science Center at San Antonio - Infectious Diseases
- University of Utah - Infectious Diseases
- University of Virginia - Acute Care Surgery
- Naval Medical Center Portsmouth - Infectious Disease Division
- EvergreenHealth Infectious Disease Service
- Providence Sacred Heart Medical Center
- Madigan Army Medical Center - Infectious Disease Clinic
- University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases
- National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center
- Seoul National University Bundang Hospital - Division of Infectious Diseases
- Seoul National University Hospital
- Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
- Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
- National University Health System - Division of Infectious Diseases
- National Centre for Infectious Diseases (NCID)
- Changi General Hospital - Clinical Trials and Research Unit (CTRU)
- Ng Teng Fong General Hospital - Infectious Disease Service
- Hospital Clinic Barcelona, Servicio de Salud Internacional
- Hospital Germans Trias i Pujol - Servei Malalties Infeccioses
- Hospital Clinico San Carlos - Enfermedades Infecciosas
- Royal Sussex County Hospital - Department of Intensive Care Medicine
- Saint Thomas' Hospital - Directorate of Infection
- St. James's University Hospital - Infectious Diseases
- Royal Victoria Infirmary - Department of Infectious Diseases
- John Radcliffe Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Remdesivir plus Baricitinib
Remdesivir plus Placebo
200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course.
200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course.