Immune Modulators for Treating COVID-19 (ACTIV-1 IM)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Infliximab; Drug: Remdesivir; Drug: Abatacept; Drug: cenicriviroc (closed to enrollment as of 3-Sep-2021)

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.

• Study Type: Interventional
• Enrollment (Actual): 1971
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1221ADC
    • Hospital Ramos Mejia
  • Cordoba, Argentina, 5000
    • Hospital Rawson
  • Córdoba, Argentina, X5000JHGQ
    • Sanatorio Allende
  • Rosario, Argentina, 2000
    • Sanatorio Britanico
  • Santa Fe, Argentina, S3000
    • Sanatorio Diagnóstico/ Instituto del Buen Aire
  • Buenos Aires
    • Bahía Blanca, Buenos Aires, Argentina, 8000
      • Hospital Interzonal Dr Jose Penna Bahia Blanca
    • Caba, Buenos Aires, Argentina, C1048
      • Sanatorio Ramon Cereijo
    • La Plata, Buenos Aires, Argentina, B1900
      • Instituto Medico Platense
  • Rio Negro
    • Villa Regina, Rio Negro, Argentina, 8336
      • Clinica Central S.A.
• Brazil
  • DF
    • Brasília, DF, Brazil, 71681-603
      • Hospital Brasilia
  • MG
    • Belo Horizonte, MG, Brazil, 30110-934
      • Hospital Felicio Rocho
  • Rio De Janeiro / RJ
    • Rio De Janeiro, Rio De Janeiro / RJ, Brazil, 22211-230
      • Instituto DOR de Ensino e Pesquisa Hospital Glória D'Or
  • Rio Grande D Sul /RS
    • Porto Alegre, Rio Grande D Sul /RS, Brazil, 90160-092
      • Hospital Ernesto Dornelles
  • Rio Grande Do Sul / RS
    • Porto Alegre, Rio Grande Do Sul / RS, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre HCPA
  • Rio Grande Do Sul/RS
    • Porto Alegre, Rio Grande Do Sul/RS, Brazil, 90020-090
      • Santa Casa de Misericordia de Porto Alegre
  • São Paulo/SP
    • Campinas, São Paulo/SP, Brazil, 13060-904
      • Hospital e Maternidade Celso Pierro - PUC Campinas
• Mexico
  • Guadalajara Jalisco
    • Guadalajara, Guadalajara Jalisco, Mexico, CP 44340
      • Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
  • Monterrey
    • Nuevo León, Monterrey, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
• Peru
  • Chiclayo, Peru, 1400
    • Hospital Regional Lambayeque
  • Lima, Peru, 15007
    • Hospitala Nacional Hipólito Unánue
  • Lima, Peru, 15082
    • Hospital Nacional Aezobispo Loayza
  • Lima, Peru, 15131
    • Hospital de Chancay y Servicios Basicos de Salud
  • Piura, Peru
    • Clínica Belén SANNA
  • Lima/Lima
    • Lima, Lima/Lima, Peru, 51
      • Hospital Central FAP
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas Medical Sciences
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinical Medical Group
    • Los Angeles, California, United States, 90095
      • UCLA - Ronald Reagan Medical Center
    • Moreno Valley, California, United States, 92555
      • Riverside University
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • Palo Alto, California, United States, 94303
      • Stanford University Medical Center
    • Santa Monica, California, United States, 06037
      • UCLA Medical Center- Santa Monica
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32218
      • University of Florida-Jacksonville
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane School Of Medicine
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21202
      • Johns Hopkins Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Worcester, Massachusetts, United States, 01655
      • U Mass Memorial Medical Center
    • Worcester, Massachusetts, United States, 01655
      • U Mass University Medical Center
  • Michigan
    • Alma, Michigan, United States, 48640
      • MidMichigan Medical Center- Gratiot
    • Midland, Michigan, United States, 48670
      • MidMichigan Medical Center - Midland
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Hospital
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers New Jersey Medical School
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU Brooklyn
    • Buffalo, New York, United States, 14203
      • University at Buffalo
    • Flushing, New York, United States, 11355
      • Flushing Hospital Medical Center
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • Long Island City, New York, United States, 10016
      • NYU Long Island
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10037
      • Harlem Hospital Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Potsdam, New York, United States, 13676
      • St Lawrence Health System
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center-Strong Memorial Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina - Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Saint Vincent Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Wyomissing, Pennsylvania, United States, 19610
      • Reading Hospital Study
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera McKennan Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Health System Clinical Research Institute
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center - Houston
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • Tyler, Texas, United States, 75708
      • University of Texas Health Center at Tyler
    • Tyler, Texas, United States, 75701
      • Trinity Mother Frances Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • West Virginia University
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Admitted to a hospital or awaiting admission in the ED with symptoms suggestive of COVID-19.
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 adults ≥18 years of age at time of enrollment.
5. 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.

6. 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.
7. 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.
8. 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:

1. ALT or AST >10 times the upper limit of normal.

2. 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.

3. Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 103/μL or <1.0 GI/L).
4. Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 103/μL or <0.20 GI/L)
5. Pregnancy or breast feeding.
6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
7. Known allergy to any study medication.

8. 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.

9. 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).

10. 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.

11. 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.
12. Severe hepatic impairment (defined as liver cirrhosis Child stage C).

13. 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.

14. In the Investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care + infliximab or matching placebo; infliximab (single dose IV 5mg/kg given on day 1) or matching placebo	Drug: Infliximab; study drug or matching placebo; Other Names: remicade; Drug: Remdesivir; Standard of Care
Active Comparator: Standard of Care + abatacept or matching placebo; abatacept (single dose IV 10 mg/kg up to 1,000 mg given on day 1) or matching placebo	Drug: Remdesivir; Standard of Care; Drug: Abatacept; study drug or matching placebo; Other Names: orencia
Active Comparator: Standard of Care + cenicriviroc or matching placebo (closed to enrollment as of 3-Sep-2021); 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	Drug: Remdesivir; Standard of Care; Drug: cenicriviroc (closed to enrollment as of 3-Sep-2021); study drug or matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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): Death;; Hospitalized, on invasive mechanical ventilation or ECMO;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, requiring supplemental oxygen;; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);; 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.; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized,	Day 14
Mortality Through 28 Days	mortality at day 28	Day 1-28
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): Death;; Hospitalized, on invasive mechanical ventilation or ECMO;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, requiring supplemental oxygen;; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);; 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.; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized,	Day 28
Mortality Through 14 Days	mortality at day 14	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	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): Death;; Hospitalized, on invasive mechanical ventilation or ECMO;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, requiring supplemental oxygen;; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);; 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.; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.	Day 1-day 28
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): Death;; Hospitalized, on invasive mechanical ventilation or ECMO;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, requiring supplemental oxygen;; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical in-patient care (COVID-19 related or otherwise);; 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.; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.	Day 1- day 28
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)	Day 0 to day 2
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)	Day 0 to day 4
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)	Day 0 to day 7
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)	Day 0 to day 10
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)	Day 0 to day 14
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)	Day 0 to day 21
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)	Day 0 to day 28
Duration (Days) Alive and Free of Supplemental Oxygen	Days alive and free of supplemental oxygen	Day 1 to day 28
Number of Patients With New Supplemental Oxygen Use	Number of patients with new supplemental oxygen use	Day 1-day 28
Duration (Days) Alive and Free of Non-invasive Ventilation/ High Flow Oxygen	Days alive and free of non-invasive ventilation/ high flow oxygen	Day 1 to day 28
Number of Patients With New Non-invasive Ventilation/High Flow Oxygen Use	Number of patients with new non-invasive ventilation/high flow oxygen use	Day 1-day 28
Duration (Days) Alive and Free of Invasive Mechanical Ventilation or ECMO	Days alive and free of invasive mechanical ventilation or ECMO	Day 1 to day 28
Number of Patients With New Mechanical Ventilation or ECMO Use	Number of patients with new mechanical ventilation or ECMO use	Day 1 to day 28
Duration (Days) Alive and Out of the Hospital	Days alive and out of the hospital	Through day 28
Number of Patients With SAEs Through Day 28	Cumulative Incidence of SAEs through day 28	Day 28
Number of Patients With Grade 3 and 4 Adverse Events	Cumulative incidence of adverse events of grade 3 and 4	Day 28
Number of Patients With Adverse Events Leading to Dose Modification	Number of patients with adverse events (serious and non serious) leading to dose modification	Day 1-28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with National Early Warning Scores (NEWS) <=2	time to discharge or to a NEWS of <=2 and maintained for 24 hours	Days 3, 5, 8, 11, 15, and 29

Collaborators and Investigators

• Sponsor: Daniel Benjamin
• Collaborators: National Center for Advancing Translational Sciences (NCATS); Biomedical Advanced Research and Development Authority
• Investigators: Principal Investigator: Daniel K Benjamin, MD, PhD, Duke University; Study Chair: Bill Powderly, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Kreuzberger 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.
• 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. 2022 Sep 26:2022.09.22.22280247. doi: 10.1101/2022.09.22.22280247. Preprint.
• O'Halloran J, Kedar E, Anstrom KJ, McCarthy MW, Ko ER, Segura Nunez P, Boucher C, Smith PB, Panettieri RA, Mendivil Tuchia de Tai S, Maillo M, Khan A, Mena Lora AJ, Salathe M, Capo G, Rodriguez Gonzalez D, Patterson TF, Palma C, Ariza H, Patelli Lima M, Lachiewicz AM, Blamoun J, Nannini E, Sprinz E, Mykietiuk A, Alicic R, Rauseo AM, Wolfe CR, Wittig 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. Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19. medRxiv. 2022 Sep 26:2022.09.22.22280245. doi: 10.1101/2022.09.22.22280245. Preprint.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): January 30, 2022
• Study Completion (Actual): March 5, 2022

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: COVID19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Immunological; Dermatologic Agents; Immune Checkpoint Inhibitors; CCR5 Receptor Antagonists; Tumor Necrosis Factor Inhibitors; Infliximab; Abatacept; Remdesivir; Cenicriviroc
• Other Study ID Numbers: Pro00106301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No