Immune Modulators for Treating COVID-19
ACTIV-1 IM
Randomized Master Protocol for Immune Modulators for Treating COVID-19
1 other identifier
interventional
1,971
5 countries
91
Brief Summary
ACTIV-1 IM is a master protocol designed to evaluate multiple investigational agents for the treatment of moderately or severely ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The research objectives are to evaluate each agent with respect to speed of recovery, mortality, illness severity, and hospital resource utilization. Each agent will be evaluated as add-on therapy to the standard of care (SoC) in use at the local clinics, including remdesivir (provided). The SoC may change during the course of the study based on other research findings. Comparisons of the agents among themselves is not a research objective. The study population corresponds to moderately and severely ill patients infected with the coronavirus disease 2019 (COVID-19) virus. Recruitment will target patients already hospitalized for treatment of COVID-19 infection as well as patients being treated for COVID-19 infection in Emergency Departments while waiting to be admitted to the hospital. Patients both in and out of the ICU are included in the study population.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 covid19
Started Oct 2020
Typical duration for phase_3 covid19
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2020
CompletedStudy Start
First participant enrolled
October 15, 2020
CompletedFirst Posted
Study publicly available on registry
October 20, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 5, 2022
CompletedResults Posted
Study results publicly available
April 21, 2023
CompletedSeptember 25, 2023
September 1, 2023
1.3 years
September 23, 2020
January 23, 2023
September 14, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Had Recovered by Day 28
Time to recovery by day 28. The number of participants who have recovered by day 28.
Days 1-28
Secondary Outcomes (23)
Number of Participants With Clinical Status for Day 14 Using an 8 Point Ordinal Scale
Day 14
Mortality Through 28 Days
Day 1-28
Number of Participants With Clinical Status for Day 28 Using an 8 Point Ordinal Scale
Day 28
Mortality Through 14 Days
Day 1-14
Number of Participants Who Met a One Point Improvement in One Category From Day 0 (Baseline) to Day 28 Using an 8-point Ordinal Scale
Day 1-day 28
- +18 more secondary outcomes
Study Arms (3)
Standard of Care + infliximab or matching placebo
ACTIVE COMPARATORinfliximab (single dose IV 5mg/kg given on day 1) or matching placebo
Standard of Care + abatacept or matching placebo
ACTIVE COMPARATORabatacept (single dose IV 10 mg/kg up to 1,000 mg given on day 1) or matching placebo
Standard of Care + cenicriviroc or matching placebo (closed to enrollment as of 3-Sep-2021)
ACTIVE COMPARATORcenicriviroc \[tablet, Day 1/Loading Dose: 450 mg (300mg morning and 150mg evening) Day 2 - 29/Maintenance Dose: 300 mg (150 mg BID) through Day 29\]. or matching placebo
Interventions
study drug or matching placebo
study drug or matching placebo
Standard of Care
study drug or matching placebo
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (91)
Banner University Medical Center
Phoenix, Arizona, 85006, United States
University of Arkansas Medical Sciences
Little Rock, Arkansas, 72205, United States
Scripps Clinical Medical Group
La Jolla, California, 92037, United States
UCLA - Ronald Reagan Medical Center
Los Angeles, California, 90095, United States
Riverside University
Moreno Valley, California, 92555, United States
UC Irvine Medical Center
Orange, California, 92868, United States
Stanford University Medical Center
Palo Alto, California, 94303, United States
UCLA Medical Center- Santa Monica
Santa Monica, California, 06037, United States
Medstar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
University of Florida-Jacksonville
Jacksonville, Florida, 32218, United States
University of Illinois at Chicago
Chicago, Illinois, 60607, United States
Northwestern University
Chicago, Illinois, 60611, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Tulane School of Medicine
New Orleans, Louisiana, 70112, United States
University Medical Center New Orleans
New Orleans, Louisiana, 70112, United States
Ochsner Medical Center
New Orleans, Louisiana, 70121, United States
Anne Arundel Medical Center
Annapolis, Maryland, 21401, United States
Johns Hopkins Medical Center
Baltimore, Maryland, 21202, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
U Mass Memorial Medical Center
Worcester, Massachusetts, 01655, United States
U Mass University Medical Center
Worcester, Massachusetts, 01655, United States
MidMichigan Medical Center- Gratiot
Alma, Michigan, 48640, United States
MidMichigan Medical Center - Midland
Midland, Michigan, 48670, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
University of Missouri Health Care
Columbia, Missouri, 65212, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Trinitas Hospital
Elizabeth, New Jersey, 07207, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Rutgers New Jersey Medical School
New Brunswick, New Jersey, 08901, United States
NYU Brooklyn
Brooklyn, New York, 11220, United States
University at Buffalo
Buffalo, New York, 14203, United States
Flushing Hospital Medical Center
Flushing, New York, 11355, United States
Jamaica Hospital Medical Center
Jamaica, New York, 11418, United States
NYU Long Island
Long Island City, New York, 10016, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Harlem Hospital Center
New York, New York, 10037, United States
Weill Cornell Medicine
New York, New York, 10065, United States
St Lawrence Health System
Potsdam, New York, 13676, United States
University of Rochester Medical Center-Strong Memorial Hospital
Rochester, New York, 14642, United States
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Duke University
Durham, North Carolina, 27710, United States
Wake Forest University
Winston-Salem, North Carolina, 27157, United States
Mercy Saint Vincent Medical Center
Toledo, Ohio, 43608, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Reading Hospital Study
Wyomissing, Pennsylvania, 19610, United States
Avera McKennan Hospital
Sioux Falls, South Dakota, 57105, United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Methodist Health System Clinical Research Institute
Dallas, Texas, 75203, United States
University of Texas Health Science Center - Houston
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Trinity Mother Frances Hospital
Tyler, Texas, 75701, United States
University of Texas Health Center at Tyler
Tyler, Texas, 75708, United States
University of Utah
Salt Lake City, Utah, 84108, United States
Virginia Commonwealth University Medical Center
Richmond, Virginia, 23298, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Providence Medical Research Center
Spokane, Washington, 99204, United States
West Virginia University
Morgantown, West Virginia, 26505, United States
Gundersen Health System
La Crosse, Wisconsin, 54601, United States
Hospital Interzonal Dr Jose Penna Bahia Blanca
Bahía Blanca, Buenos Aires, 8000, Argentina
Sanatorio Ramon Cereijo
CABA, Buenos Aires, C1048, Argentina
Instituto Medico Platense
La Plata, Buenos Aires, B1900, Argentina
Clinica Central S.A.
Villa Regina, Río Negro Province, 8336, Argentina
Hospital Ramos Mejia
Buenos Aires, C1221ADC, Argentina
Hospital Rawson
Córdoba, 5000, Argentina
Sanatorio Allende
Córdoba, X5000JHGQ, Argentina
Sanatorio Britanico
Rosario, 2000, Argentina
Sanatorio Diagnóstico/ Instituto del Buen Aire
Santa Fe, S3000, Argentina
Hospital Brasília
Brasília, Federal District, 71681-603, Brazil
Hospital Felício Rocho
Belo Horizonte, Minas Gerais, 30110-934, Brazil
Instituto DOR de Ensino e Pesquisa Hospital Glória D'Or
Rio de Janeiro, Rio de Janeiro / RJ, 22211-230, Brazil
Hospital Ernesto Dornelles
Porto Alegre, Rio Grande D Sul /RS, 90160-092, Brazil
Hospital de Clinicas de Porto Alegre HCPA
Porto Alegre, Rio Grande Do Sul / RS, 90035-903, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande Do Sul/RS, 90020-090, Brazil
Hospital e Maternidade Celso Pierro - PUC Campinas
Campinas, São Paulo/SP, 13060-904, Brazil
Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
Guadalajara, Guadalajara Jalisco, CP 44340, Mexico
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Nuevo León, Monterrey, 64460, Mexico
Hospital Central FAP
Lima, Lima/Lima, 51, Peru
Hospital Regional Lambayeque
Chiclayo, 1400, Peru
Hospitala Nacional Hipólito Unánue
Lima, 15007, Peru
Hospital Nacional Aezobispo Loayza
Lima, 15082, Peru
Hospital de Chancay y Servicios Basicos de Salud
Lima, 15131, Peru
Clínica Belén SANNA
Piura, Peru
Related Publications (6)
Lachiewicz AM, Shah M, Der T, Cyr D, Al-Khalidi HR, Lindsell C, Iyer V, Khan A, Panettieri R, Rauseo AM, Maillo M, Schmid A, Jagpal S, Powderly WG, Bozzette SA; ACTIV-1 IM study group members. Resource Use in the Randomized Master Protocol for Immune Modulators for Treating COVID-19 (ACTIV-1 IM): A Secondary Data Analysis. CHEST Crit Care. 2024 Dec;2(4):100095. doi: 10.1016/j.chstcc.2024.100095. Epub 2024 Aug 22.
PMID: 39610848DERIVEDBalevic SJ, Benjamin DK Jr, Powderly WG, Smith PB, Gonzalez D, McCarthy MW, Shaw LK, Lindsell CJ, Bozzette S, Williams D, Linas BP, Blamoun J, Javeri H, Hornik CP; ACTIV-1 IM Study Group. Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e247615. doi: 10.1001/jamanetworkopen.2024.7615.
PMID: 38662372DERIVEDO'Halloran JA, Ko ER, Anstrom KJ, Kedar E, McCarthy MW, Panettieri RA Jr, Maillo M, Nunez PS, Lachiewicz AM, Gonzalez C, Smith PB, de Tai SM, Khan A, Lora AJM, Salathe M, Capo G, Gonzalez DR, Patterson TF, Palma C, Ariza H, Lima MP, Blamoun J, Nannini EC, Sprinz E, Mykietiuk A, Alicic R, Rauseo AM, Wolfe CR, Witting B, Wang JP, Parra-Rodriguez L, Der T, Willsey K, Wen J, Silverstein A, O'Brien SM, Al-Khalidi HR, Maldonado MA, Melsheimer R, Ferguson WG, McNulty SE, Zakroysky P, Halabi S, Benjamin DK Jr, Butler S, Atkinson JC, Adam SJ, Chang S, LaVange L, Proschan M, Bozzette SA, Powderly WG; ACTIV-1 IM Study Group Members. Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA. 2023 Jul 25;330(4):328-339. doi: 10.1001/jama.2023.11043.
PMID: 37428480DERIVEDKo ER, Anstrom KJ, Panettieri RA, Lachiewicz AM, Maillo M, O'Halloran JA, Boucher C, Smith PB, McCarthy MW, Segura Nunez P, Mendivil Tuchia de Tai S, Khan A, Mena Lora AJ, Salathe M, Kedar E, Capo G, Rodriguez Gonzalez D, Patterson TF, Palma C, Ariza H, Patelli Lima M, Blamoun J, Nannini EC, Sprinz E, Mykietiuk A, Wang JP, Parra-Rodriguez L, Der T, Willsey K, Benjamin DK, Wen J, Zakroysky P, Halabi S, Silverstein A, McNulty SE, O'Brien SM, Al-Khalidi HR, Butler S, Atkinson J, Adam SJ, Chang S, Maldonado MA, Proscham M, LaVange L, Bozzette SA, Powderly WG; ACTIV-1 IM study group members. Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19. medRxiv [Preprint]. 2022 Sep 26:2022.09.22.22280247. doi: 10.1101/2022.09.22.22280247.
PMID: 36203544DERIVEDO'Halloran JA, Kedar E, Anstrom KJ, McCarthy MW, Ko ER, Nunez PS, Boucher C, Smith PB, Panettieri RA, de Tai SMT, Maillo M, Khan A, Mena Lora AJ, Salathe M, Capo G, Gonzalez DR, Patterson TF, Palma C, Ariza H, Lima MP, Lachiewicz AM, Blamoun J, Nannini EC, Sprinz E, Mykietiuk A, Alicic R, Rauseo AM, Wolfe CR, Witting B, Benjamin DK, McNulty SE, Zakroysky P, Halabi S, Butler S, Atkinson J, Adam SJ, Melsheimer R, Chang S, LaVange L, Proschan M, Bozzette SA, Powderly WG; ACTIV-1 IM study group members. Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19. medRxiv [Preprint]. 2022 Sep 26:2022.09.22.22280245. doi: 10.1101/2022.09.22.22280245.
PMID: 36172138DERIVEDKreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PMID: 34473343DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- William G. Powderly MD
- Organization
- Washington University in St. Louis
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel K Benjamin, MD, PhD
Duke University
- STUDY CHAIR
Bill Powderly, MD
Washington University School of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Study Drug and Matching Placebo
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Kiser-Arena Distinguished Professor, Duke University Pediatrics
Study Record Dates
First Submitted
September 23, 2020
First Posted
October 20, 2020
Study Start
October 15, 2020
Primary Completion
January 30, 2022
Study Completion
March 5, 2022
Last Updated
September 25, 2023
Results First Posted
April 21, 2023
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will not share