Immune Modulators for Treating COVID-19 (ACTIV-1 IM)
Covid19
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID19
Eligibility Criteria
Inclusion Criteria:
- Admitted to a hospital or awaiting admission in the ED 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 adults ≥18 years of age at time of enrollment.
- Has laboratory-confirmed (within 14 days prior to enrollment) SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen.
Ongoing illness of any duration, and at least one of the following:
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- Blood oxygen saturation (SpO2) ≤94% on room air, OR
- Requiring supplemental oxygen, OR
- Requiring mechanical ventilation or ECMO.
- Women of childbearing potential must agree to either abstinence or use of at least one primary form of contraception not including hormonal contraception from the time of screening through Day 60.
- Agrees to not to participate in another interventional trial for the treatment of COVID-19 through Day 60.
Exception 1: Participant may co-enroll in ACTIV-4 (ACTIV-4A and ACTIV-4C). Exception 2: Participants in ACTIV-2 who have been hospitalized may be enrolled in ACTIV-1 as long as ACTIV-2 study therapy has been discontinued. They will remain in ACTIV-2 follow-up.
Exception 3: If participant is already participating in a COVID-19 vaccine trial but develops COVID-19 disease that requires hospitalization, participant is eligible for this study, assuming all other inclusion/exclusion criteria are met.
Exclusion Criteria:
- ALT or AST >10 times the upper limit of normal.
Estimated glomerular filtration rate (eGFR) <30 mL/min (including patients receiving hemodialysis or hemofiltration).
Exception: Participants with an eGFR <30 mL/min may enroll as long as their renal insufficiency has been stable without renal replacement therapy for ≥1 month and they are not current candidates for renal replacement therapy. These participants will not receive remdesivir.
- Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 103/μL or <1.0 GI/L).
- Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 103/μL 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.
- Known allergy to any study medication.
Received cytotoxic or biologictargeted immune-modulator treatments (such as anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], anti-IL-17, or T-cell or B-cell targeted therapies ([e.g., rituximab), tyrosine kinase], JAK inhibitors [including baricitinib,], TNF inhibitors, or interferon) within 4 weeks or 5 half-lives prior to screening., whichever is longer. Steroid dependency, defined as need for prednisone at a dose >10 mg (or equivalent) for >1 month within 2 weeks of screening, is exclusionary. Note Exception 1: Dexamethasone (at a dose of 6 mg per day for up to 10 days) is permitted for the treatment of COVID-19 in patients who are already mechanically ventilated and in patients who require supplemental oxygen at screening, but who are not mechanically ventilated in accordance with national guidelines. Note Exception 2: Infusion of convalescent plasma given for treatment of COVID-19 while on-study is also allowed.
Exception 3: Monoclonal antibody therapy given for COVID-19 treatment at any time prior to enrollment is also allowed.
- BasedKnown or suspected history of untreated tuberculosis (TB). TB diagnosis may be suspected based on medical history and concomitant therapies that would suggest TB infection, have suspected clinical diagnosis of current active tuberculosis (TB) or, if. Participants are also excluded if they have known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
Based on medical history and concomitant therapies that would suggest infection,Known or suspected serious, active bacterial, fungal, or viral (infection (excepting SARS-CoV-2 and including, but not limited to, active HBV, HCV, or HIV/AIDS). with the latter defined as a CD4 count <200 or an unsuppressed HIV viral load), or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
Note: Broad-spectrum empiric antibiotic usage does not exclude participation.
- Have received any live vaccine (that is,or live attenuated) within 3 months before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note Exception: Use of prior non-live (inactivated) vaccinations is allowed for all participants, including any vaccine for COVID-19.
- Severe hepatic impairment (defined as liver cirrhosis Child stage C).
CurrentKnown severe heart failure (New York Heart Association [NYHA] III-IV).) or new-onset left-systolic or global cardiac dysfunction in the setting of COVID-19.
Exception: Right-sided heart dysfunction or pulmonary hypertension thought related to COVID-19 is permitted.
- In the Investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.
Sites / Locations
- Banner University Medical Center
- University of Arkansas Medical Sciences
- Scripps Clinical Medical Group
- UCLA - Ronald Reagan Medical Center
- Riverside University
- UC Irvine Medical Center
- Stanford University Medical Center
- UCLA Medical Center- Santa Monica
- Medstar Washington Hospital Center
- University of Florida-Jacksonville
- University of Illinois at Chicago
- Northwestern University
- Loyola University Medical Center
- University of Iowa
- University of Kansas
- University of Kentucky
- Tulane School of Medicine
- University Medical Center New Orleans
- Ochsner Medical Center
- Anne Arundel Medical Center
- Johns Hopkins Medical Center
- Tufts Medical Center
- Brigham and Women's Hospital
- Boston Medical Center
- Beth Israel Deaconess Medical Center
- U Mass Memorial Medical Center
- U Mass University Medical Center
- MidMichigan Medical Center- Gratiot
- MidMichigan Medical Center - Midland
- Mayo Clinic
- University of Mississippi Medical Center
- University of Missouri Health Care
- Washington University School of Medicine
- Trinitas Hospital
- Hackensack University Medical Center
- Rutgers New Jersey Medical School
- NYU Brooklyn
- University at Buffalo
- Flushing Hospital Medical Center
- Jamaica Hospital Medical Center
- NYU Long Island
- New York University Langone Medical Center
- Harlem Hospital Center
- Weill Cornell Medicine
- St Lawrence Health System
- University of Rochester Medical Center-Strong Memorial Hospital
- University of North Carolina - Chapel Hill
- Duke University
- Wake Forest University
- Mercy Saint Vincent Medical Center
- University of Oklahoma Health Sciences Center
- Oregon Health and Science University
- Temple University Hospital
- Reading Hospital Study
- Avera McKennan Hospital
- University of Tennessee Medical Center
- Methodist Health System Clinical Research Institute
- University of Texas Health Science Center - Houston
- University of Texas Health Science Center at San Antonio
- Trinity Mother Frances Hospital
- University of Texas Health Center at Tyler
- University of Utah
- Virginia Commonwealth University Medical Center
- University of Washington Medical Center
- Providence Medical Research Center
- West Virginia University
- Gundersen Health System
- Hospital Interzonal Dr Jose Penna Bahia Blanca
- Sanatorio Ramon Cereijo
- Instituto Medico Platense
- Clinica Central S.A.
- Hospital Ramos Mejia
- Hospital Rawson
- Sanatorio Allende
- Sanatorio Britanico
- Sanatorio Diagnóstico/ Instituto del Buen Aire
- Hospital Brasília
- Hospital Felício Rocho
- Instituto DOR de Ensino e Pesquisa Hospital Glória D'Or
- Hospital Ernesto Dornelles
- Hospital de Clinicas de Porto Alegre HCPA
- Santa Casa de Misericordia de Porto Alegre
- Hospital e Maternidade Celso Pierro - PUC Campinas
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
- Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
- Hospital Central FAP
- Hospital Regional Lambayeque
- Hospitala Nacional Hipólito Unánue
- Hospital Nacional Aezobispo Loayza
- Hospital de Chancay y Servicios Basicos de Salud
- Clínica Belén SANNA
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Active Comparator
Active Comparator
Standard of Care + infliximab or matching placebo
Standard of Care + abatacept or matching placebo
Standard of Care + cenicriviroc or matching placebo (closed to enrollment as of 3-Sep-2021)
infliximab (single dose IV 5mg/kg given on day 1) or matching placebo
abatacept (single dose IV 10 mg/kg up to 1,000 mg given on day 1) or matching placebo
cenicriviroc [tablet, Day 1/Loading Dose: 450 mg (300mg morning and 150mg evening) Day 2 - 29/Maintenance Dose: 300 mg (150 mg BID) through Day 29]. or matching placebo