Abatacept in Immune Checkpoint Inhibitor Myocarditis

NCT05335928 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2021P003690
• Study Type: interventional
• Target: 390
• Locations: 2 countries
• Sites: 31

Brief Summary

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.

Conditions

Myocarditis Acute; Cancer

Keywords

Immune checkpoint Inhibitor; Myocarditis; Abatacept; Immune therapy; Immune related adverse events

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiac events

  The rates of a composite of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmias, significant bradyarrhythmias, or incident heart failure.

  6 months

Secondary Outcomes (8)

• The individual components of the primary endpoint.

  6 months

• Myocarditis illness severity using a 7-point ordinal severity scale containing each of the individual endpoints in a hierarchical ranking order.

  6 months

• The increase in serum troponin levels

  6 months

• The combination of the rates of the primary outcome plus the proportion of patients with a troponin increase.

  6 months

• Clinical status at 90 days after first infusion of study drug

  6 months

Study Arms (2)

Abatacept plus standard of care

EXPERIMENTAL

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.

Drug: Abatacept plus

Placebo plus standard of care

PLACEBO COMPARATOR

Placebo will be administered at the same intervals.

Drug: Placebo

Interventions

Abatacept plus 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

Also known as: Orencia

Abatacept plus standard of care

Placebo DRUG

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

Placebo plus standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Aged greater than or equal to 18 years at the time of informed consent;
• 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;
• A diagnosis of myocarditis.
• Hospitalized at the time of randomization;
• 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;
• 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;
• 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;
• 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
• Must be willing and able to abide by all study requirements and restrictions.

You may not qualify if:

• 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.
• Recent (≤2 month) exposure to abatacept or belatacept.
• 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.
• Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
• 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.
• 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.
• 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.
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
• 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.
• 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.
• Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (31)

Cedars-Sinai Medical Center

Los Angeles, California, 02127, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

MedStar Health Research Institute, Georgetown University

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Franciscan Health

Indianapolis, Indiana, 46237, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536-0200, United States

RECRUITING

Maine Health

Portland, Maine, 04102, United States

RECRUITING

Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599-7075, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Lehigh Valley Health Network

Bethlehem, Pennsylvania, 18017, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Allegheny-Singer Research Institution

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 72535, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

University of West Virginia

Morgantown, West Virginia, 26506, United States

RECRUITING

Aurora St Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

RECRUITING

University of British Colombia

Vancouver, British Colombia, V5Z 1M9, Canada

RECRUITING

McMaster University

Hamilton, Ontario, L8V 1C3, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 38963866 DERIVED

MeSH Terms

Conditions

Neoplasms; Myocarditis

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Central Study Contacts

Hannah K Gilman, MS

CONTACT

6177261019; hkgilman@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Cardio-Oncology Program

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 20, 2022
• Study Start: July 2, 2022
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): April 20, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (29)