AzTrials
AzTrials

Covid19Phase 3ACTIV-1 IMNCT04593940

Immune Modulators for Treating COVID-19

A Phase 3 study testing Infliximab, Abatacept and Remdesivir in people with Covid19, run by Daniel Benjamin at 91 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
Infliximab, Abatacept and Remdesivir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,971 participants
Where
91 sitesin 5 countries
Study dates
15 Oct 2020to 5 Mar 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.

Trial locations and contacts

91 sites in 5 countries.

91 sites in 5 countries

United States67 sites

  • MidMichigan Medical Center- Gratiot

    Alma, Michigan, 48640

  • Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Johns Hopkins Medical Center

    Baltimore, Maryland, 21202

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • NYU Brooklyn

    Brooklyn, New York, 11220

  • University at Buffalo

    Buffalo, New York, 14203

  • University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599

  • University of Illinois at Chicago

    Chicago, Illinois, 60607

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Missouri Health Care

    Columbia, Missouri, 65212

  • Methodist Health System Clinical Research Institute

    Dallas, Texas, 75203

  • Duke University

    Durham, North Carolina, 27710

  • Trinitas Hospital

    Elizabeth, New Jersey, 07207

  • Flushing Hospital Medical Center

    Flushing, New York, 11355

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Texas Health Science Center - Houston

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Florida-Jacksonville

    Jacksonville, Florida, 32218

  • Jamaica Hospital Medical Center

    Jamaica, New York, 11418

  • University of Kansas

    Kansas City, Kansas, 66160

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Gundersen Health System

    La Crosse, Wisconsin, 54601

  • Scripps Clinical Medical Group

    La Jolla, California, 92037

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Arkansas Medical Sciences

    Little Rock, Arkansas, 72205

  • NYU Long Island

    Long Island City, New York, 10016

  • UCLA - Ronald Reagan Medical Center

    Los Angeles, California, 90095

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • MidMichigan Medical Center - Midland

    Midland, Michigan, 48670

  • Riverside University

    Moreno Valley, California, 92555

  • West Virginia University

    Morgantown, West Virginia, 26505

  • Rutgers New Jersey Medical School

    New Brunswick, New Jersey, 08901

  • Tulane School of Medicine

    New Orleans, Louisiana, 70112

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • New York University Langone Medical Center

    New York, New York, 10016

  • Harlem Hospital Center

    New York, New York, 10037

  • Weill Cornell Medicine

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Medical Center

    Orange, California, 92868

  • Stanford University Medical Center

    Palo Alto, California, 94303

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Banner University Medical Center

    Phoenix, Arizona, 85006

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • St Lawrence Health System

    Potsdam, New York, 13676

  • Virginia Commonwealth University Medical Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center-Strong Memorial Hospital

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84108

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCLA Medical Center- Santa Monica

    Santa Monica, California, 06037

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Avera McKennan Hospital

    Sioux Falls, South Dakota, 57105

  • Providence Medical Research Center

    Spokane, Washington, 99204

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Saint Vincent Medical Center

    Toledo, Ohio, 43608

  • Trinity Mother Frances Hospital

    Tyler, Texas, 75701

  • University of Texas Health Center at Tyler

    Tyler, Texas, 75708

  • Medstar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

  • U Mass Memorial Medical Center

    Worcester, Massachusetts, 01655

  • U Mass University Medical Center

    Worcester, Massachusetts, 01655

  • Reading Hospital Study

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Argentina9 sites

  • Hospital Interzonal Dr Jose Penna Bahia Blanca

    Bahía Blanca, Buenos Aires, 8000

  • Hospital Ramos Mejia

    Buenos Aires, C1221ADC

  • Sanatorio Ramon Cereijo

    CABA, Buenos Aires, C1048

  • Hospital Rawson

    Córdoba, 5000

  • Sanatorio Allende

    Córdoba, X5000JHGQ

  • Instituto Medico Platense

    La Plata, Buenos Aires, B1900

  • Sanatorio Britanico

    Rosario, 2000

  • Sanatorio Diagnóstico/ Instituto del Buen Aire

    Santa Fe, S3000

  • Clinica Central S.A.

    Villa Regina, Río Negro Province, 8336

Other trials in Argentina

Brazil7 sites

  • Hospital Felício Rocho

    Belo Horizonte, Minas Gerais, 30110-934

  • Hospital Brasília

    Brasília, Federal District, 71681-603

  • Hospital e Maternidade Celso Pierro - PUC Campinas

    Campinas, São Paulo/SP, 13060-904

  • Hospital Ernesto Dornelles

    Porto Alegre, Rio Grande D Sul /RS, 90160-092

  • Hospital de Clinicas de Porto Alegre HCPA

    Porto Alegre, Rio Grande Do Sul / RS, 90035-903

  • Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande Do Sul/RS, 90020-090

  • Instituto DOR de Ensino e Pesquisa Hospital Glória D'Or

    Rio de Janeiro, Rio de Janeiro / RJ, 22211-230

Other trials in Brazil

Peru6 sites

  • Hospital Regional Lambayeque

    Chiclayo, 1400

  • Hospital Central FAP

    Lima, Lima/Lima, 51

  • Hospitala Nacional Hipólito Unánue

    Lima, 15007

  • Hospital Nacional Aezobispo Loayza

    Lima, 15082

  • Hospital de Chancay y Servicios Basicos de Salud

    Lima, 15131

  • Clínica Belén SANNA

    Piura

Other trials in Peru

Mexico2 sites

  • Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"

    Guadalajara, Guadalajara Jalisco, CP 44340

  • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

    Nuevo León, Monterrey, 64460

Other trials in Mexico

About this study

Official title: Randomized Master Protocol for Immune Modulators for Treating COVID-19

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.

Read the detailed description

ACTIV-1 IM is a master protocol designed to evaluate immune modulators for the treatment of moderately or severely ill hospitalized patients infected with COVID-19. Trial participants will be assessed daily while hospitalized. If the participants are discharged from the hospital prior to Day 29, they will have follow-up study visits at Days 8, 11, 15, 22, and 29. For discharged participants, it is preferred that the Day 8, 11, 15, and 29 visits are in person to obtain safety laboratory tests and blood (serum/plasma) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the participant 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 Day 60 assessment will be conducted by phone.

The effectiveness of each therapeutic agent as add-on therapy to SoC plus remdesivir (provided) will be evaluated based on the primary endpoint of time to recovery by Day 29. The sample size requirements are based on the ability to detect a moderate improvement in time to recovery (3-4 fewer days) for each agent. A total of 788 recoveries are required for each comparison to provide approximately 85% power to detect a recovery rate ratio of 1.25. Assuming 73% of participants achieve recovery in 28 days, consistent with the ACTT-1 results, the total sample size to evaluate 1, 2, and 3 agents in ACTIV-1 IM is approximately 1080, 1620, and 2160, respectively. Because each agent is being compared to SoC with no between-agent comparisons, no multiplicity adjustments for multiple agents are planned.

The CVC arm of the study was closed to enrollment on 3-Sep-2021.

Conditions
Covid19
Being tested
Infliximab, Abatacept, Remdesivir, cenicriviroc (closed to enrollment as of 3-Sep-2021)
Keywords
COVID19
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfliximabDrug

    Also called remicade

    study drug or matching placebo

  • AbataceptDrug

    Also called orencia

    study drug or matching placebo

  • RemdesivirDrug

    Standard of Care

  • cenicriviroc (closed to enrollment as of 3-Sep-2021)Drug

    study drug or matching placebo

Study groups in NCT04593940
Study groupRoleWhat they receive
Standard of Care + infliximab or matching placeboActive comparatorinfliximab (single dose IV 5mg/kg given on day 1) or matching placebo
Receives: Drug: Infliximab; Drug: Remdesivir
Standard of Care + abatacept or matching placeboActive comparatorabatacept (single dose IV 10 mg/kg up to 1,000 mg given on day 1) or matching placebo
Receives: Drug: Abatacept; Drug: Remdesivir
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
Receives: Drug: Remdesivir; Drug: cenicriviroc (closed to enrollment as of 3-Sep-2021)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Days 1-28

Secondary outcomes (23)

  1. Number of Participants With Clinical Status for Day 14 Using an 8 Point Ordinal Scale

    8-point ordinal scale assessing clinical status (1=Death is worst, 8=not hospitalized/no limitations on activities is best) To determine a participant's clinical status using the ordinal scale their clinical status was collected at Day 15 assessing day 14.

    The scale used in this study is as follows (from worst to best):

    1. Death;
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical in-patient care; This would include those kept in hospital for quarantine/infection control/social reasons, awaiting bed in rehabilitation facility or homecare, etc.
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized,

    Measured: Day 14

  2. Mortality Through 28 Days

    mortality at day 28

    Measured: Day 1-28

  3. Number of Participants With Clinical Status for Day 28 Using an 8 Point Ordinal Scale

    8-point ordinal scale assessing clinical status (1=Death is worst, 8=not hospitalized/no limitations on activities is best) To determine a participant's clinical status using the ordinal scale their clinical status was collected at Day 29 assessing day 28.

    The scale used in this study is as follows (from worst to best):

    1. Death;
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical in-patient care; This would include those kept in hospital for quarantine/infection control/social reasons, awaiting bed in rehabilitation facility or homecare, etc.
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized,

    Measured: Day 28

  4. Mortality Through 14 Days

    mortality at day 14

    Measured: Day 1-14

  5. 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

    8-point ordinal scale assessing clinical status (1=Death is worst, 8=not hospitalized/no limitations on activities is best). Number of people who met a 1 point improvement.

    The scale used in this study is as follows (from worst to best):

    1. Death;
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical in-patient care; This would include those kept in hospital for quarantine/infection control/social reasons, awaiting bed in rehabilitation facility or homecare, etc.
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities.

    Measured: Day 1-day 28

  6. Number of Participants Who Met a One Point Improvement in Two Categories From Day 0 (Baseline) to Day 28 Using an 8-point Ordinal Scale

    8-point ordinal scale assessing clinical status (1=Death is worst, 8=not hospitalized/no limitations on activities is best). Number of people who met a two category improvement.

    The scale used in this study is as follows (from worst to best):

    1. Death;
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen;
    5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical in-patient care; This would include those kept in hospital for quarantine/infection control/social reasons, awaiting bed in rehabilitation facility or homecare, etc.
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities.

    Measured: Day 1- day 28

  7. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 2

    8-point ordinal scale assessing clinical status (1=Death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 2

  8. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 4

    8 point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 4

  9. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 7

    8-point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities=best)

    Measured: Day 0 to day 7

  10. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 10

    8-point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 10

  11. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 14

    8-point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 14

  12. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 21

    8-point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 21

  13. Mean Change in the 8-point Ordinal Scale From Day 0 to Day 28

    8-point ordinal scale assessing clinical status (1=death is worst, 8=not hospitalized/no limitations on activities is best)

    Measured: Day 0 to day 28

  14. Duration (Days) Alive and Free of Supplemental Oxygen

    Days alive and free of supplemental oxygen

    Measured: Day 1 to day 28

  15. Number of Patients With New Supplemental Oxygen Use

    Number of patients with new supplemental oxygen use

    Measured: Day 1-day 28

  16. Duration (Days) Alive and Free of Non-invasive Ventilation/ High Flow Oxygen

    Days alive and free of non-invasive ventilation/ high flow oxygen

    Measured: Day 1 to day 28

  17. Number of Patients With New Non-invasive Ventilation/High Flow Oxygen Use

    Number of patients with new non-invasive ventilation/high flow oxygen use

    Measured: Day 1-day 28

  18. Duration (Days) Alive and Free of Invasive Mechanical Ventilation or ECMO

    Days alive and free of invasive mechanical ventilation or ECMO

    Measured: Day 1 to day 28

  19. Number of Patients With New Mechanical Ventilation or ECMO Use

    Number of patients with new mechanical ventilation or ECMO use

    Measured: Day 1 to day 28

  20. Duration (Days) Alive and Out of the Hospital

    Days alive and out of the hospital

    Measured: Through day 28

  21. Number of Patients With SAEs Through Day 28

    Cumulative Incidence of SAEs through day 28

    Measured: Day 28

  22. Number of Patients With Grade 3 and 4 Adverse Events

    Cumulative incidence of adverse events of grade 3 and 4

    Measured: Day 28

  23. Number of Patients With Adverse Events Leading to Dose Modification

    Number of patients with adverse events (serious and non serious) leading to dose modification

    Measured: Day 1-28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2020
  2. Study start15 Oct 2020
  3. Primary completion30 Jan 2022
  4. Study completion5 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
ACTIV-1 IM builds upon findings and the model used for other network COVID studies. Including multiple therapeutic agents under a single protocol avoids duplication of effort in terms of infrastructure, trial governance, information systems (EDC, web-based randomization, etc.) and other aspects of study management. Implementation of the master protocol facilitates discontinuation of less promising agents and addition of possibly newly emergent agents that become available after the study begins, without stopping and starting the study itself for extended pauses. All test agents are evaluated as add-on therapies to the local SoC at each clinic. The master protocol design allows for the efficacy and safety of each agent to be determined based on comparisons with a pooled control group, consisting of patients receiving SoC plus placebo. Sharing control patients across all test agents substantially reduces the sample size requirements for the study.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,971 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04593940
Sponsor's protocol ID
Pro00106301
Acronym
ACTIV-1 IM
Status last verified
Sep 2023
First submitted
23 Sep 2020
Last updated
25 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39610848

  • Balevic 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.

    PubMed 38662372

  • O'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.

    PubMed 37428480

  • Ko 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.

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Infliximab, Abatacept and Remdesivir in people with Covid19, run by Daniel Benjamin at 91 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States, Argentina, Brazil, Peru, Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Had Recovered by Day 28 (time frame: Days 1-28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04593940, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2023.

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