Abatacept in Immune Checkpoint Inhibitor Myocarditis

NCT ID: NCT05335928

Last Updated: 2025-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-02

Study Completion Date

2027-04-20

Brief Summary

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The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.

Detailed Description

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This investigator-initiated randomized trial is being conducted to test whether abatacept, as compared to placebo, is associated with a reduction in MACE among participants who develop myocarditis after treatment with an ICI. Immune checkpoint inhibitors leverage the immune system to treat a wide variety of cancers. Myocarditis is an uncommon immune related adverse event (irAE) secondary to treatment with an ICI. The guideline recommended treatment for ICI myocarditis is cessation of the ICI and administration of corticosteroids. However, despite administration of corticosteroids, the rate of MACE with ICI myocarditis is high. Data from multiple independent international cohorts have shown that the rate of MACE with ICI myocarditis despite administration of corticosteroids ranges from 25-50%.For comparison, the rate of MACE with myocarditis unrelated to an ICI is \<5%.

Abatacept is a selective co-stimulation modulator that inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking its interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. In animal studies of ICI myocarditis, the administration of abatacept led to a reduction in cardiac immune activation and an increase in survival. In retrospective unpublished clinical data, the administration of abatacept to participants with ICI myocarditis on corticosteroids was associated with a reduction in risk of MACE. There are no prospective studies testing whether abatacept is effective among participants with ICI myocarditis. Therefore, the primary aim of this trial is to test in a randomized double-blind placebo-controlled study whether abatacept, administered concurrently with corticosteroids, is associated with a reduction in MACE among participants with recently diagnosed ICI myocarditis

Conditions

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Myocarditis Acute Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Abatacept plus standard of care

Abatacept (10 mg/kg) will be administered IV after randomization, again at 24 hours after first study drug treatment, at 14 days after first study drug treatment and an optional 4th dose at 28 days.

Group Type EXPERIMENTAL

Abatacept plus

Intervention Type DRUG

Up to 4 study drug infusions at 10 mg/kg, IV

Drug: Standard of care Local standard of care per written policies or guidelines Other Name: SoC

Placebo plus standard of care

Placebo will be administered at the same intervals.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Drug: Standard of care Local standard of care per written policies or guidelines Other Name: SoC

Interventions

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Abatacept plus

Up to 4 study drug infusions at 10 mg/kg, IV

Drug: Standard of care Local standard of care per written policies or guidelines Other Name: SoC

Intervention Type DRUG

Placebo

Drug: Standard of care Local standard of care per written policies or guidelines Other Name: SoC

Intervention Type DRUG

Other Intervention Names

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Orencia

Eligibility Criteria

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Inclusion Criteria

1. Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;
2. Aged greater than or equal to 18 years at the time of informed consent;
3. Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;
4. A diagnosis of myocarditis.
5. Hospitalized at the time of randomization;
6. On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;
7. Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;
8. The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:

* Total white blood cell (WBC) count \>2,500/μl
* Absolute neutrophil count (ANC) \>1,500/μL
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \<20 times the upper limit of the institutional normal ranges;
9. Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and
10. Must be willing and able to abide by all study requirements and restrictions.

Exclusion Criteria

1. Must not have experienced any of the following (as defined in the section on the primary endpoint) in the 30-day period prior to randomization:

* A sudden cardiac arrest
* Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II second degree atrioventricular block or third degree (complete) atrio-ventricular (AV) block, for which an intervention with a temporary or permanent pacemaker is completed or recommended).
* A significant tachyarrhythmia (ventricular fibrillation of any duration or sustained ventricular tachycardia (\>30 seconds, \>120 beats per minute); or a ventricular tachyarrhythmia requiring intervention.
2. Recent (≤2 month) exposure to abatacept or belatacept.
3. Concurrent or recent (≤2 month) use of the following non-corticosteroid immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The use of intravenous immunoglobulin is permitted prior to randomization and during study treatment.
4. Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
5. Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
6. Male who is considering fathering a child or donating sperm during the study or for approximately 30 days after the last dose of study drug.
7. Any active, chronic, or recurrent viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study. These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, and disseminated (even a single episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection will be excluded. This is defined as the period of ongoing symptoms in the setting of a positive Covid-19 test, or until 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications.
8. Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
9. Receipt of any live vaccine within four weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.
10. Any medical condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the participant by participating in the study.
11. Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Tomas G. Neilan, MD

Director, Cardio-Oncology Program

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

University of California Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

MedStar Health Research Institute, Georgetown University

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Franciscan Health

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

University of Kentucky

Lexington, Kentucky, United States

Site Status RECRUITING

Maine Health

Portland, Maine, United States

Site Status RECRUITING

Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Boston Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Lehigh Valley Health Network

Bethlehem, Pennsylvania, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Allegheny-Singer Research Institution

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

University of West Virginia

Morgantown, West Virginia, United States

Site Status RECRUITING

Aurora St Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status RECRUITING

University of British Colombia

Vancouver, British Colombia, Canada

Site Status RECRUITING

McMaster University

Hamilton, Ontario, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Hannah K Gilman, MS

Role: CONTACT

6177261019

Facility Contacts

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Kiranbir Josan, MD

Role: primary

Eric Yang, MD

Role: primary

Hayder Hashim

Role: primary

Mohammed v

Role: primary

Jeanne DeCara

Role: primary

Ryan Daly

Role: primary

Charles Porter

Role: primary

Amit Arbune

Role: primary

Maxwell Afari

Role: primary

Joban Vaishnav

Role: primary

Daniel Zlotoff, MD, PhD

Role: primary

6177262000

Abul Aritizia, MD

Role: primary

Omar Siddiqi

Role: primary

Anju Nohria, MD

Role: primary

Salim Hayek, MD

Role: primary

Joerg Herrmann

Role: primary

Amna Zafar

Role: primary

Jayant Raikhelkar

Role: primary

Dipti Gupta, MD

Role: primary

Brian Jensen, MD

Role: primary

Rohit Moudgil

Role: primary

Nicholas Trask

Role: primary

Michael Fradley

Role: primary

Valentyna Ivanova

Role: primary

Saketh Nadimpalli

Role: primary

Nicolas Palaskas

Role: primary

Anees Daud, MD

Role: primary

Brijesh Patel

Role: primary

Manmeet Singh

Role: primary

Margot Davis

Role: primary

Darryl Leong

Role: primary

References

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Heymans S, Van Linthout S, Kraus SM, Cooper LT, Ntusi NAB. Clinical Characteristics and Mechanisms of Acute Myocarditis. Circ Res. 2024 Jul 5;135(2):397-411. doi: 10.1161/CIRCRESAHA.124.324674. Epub 2024 Jul 4.

Reference Type DERIVED
PMID: 38963866 (View on PubMed)

Other Identifiers

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2021P003690

Identifier Type: -

Identifier Source: org_study_id

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