Abatacept Compared to Placebo for the Treatment of Immune Checkpoint Inhibitor Associated Myocarditis, ATRIUM Study

Inclusion Criteria

• 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 >= 18 years at the time of informed consent
• Recent use of a Food and Drug Administration (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 =< 2 weeks of informed consent based on standardized International Cardio-Oncology Society Guideline criteria
• 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 administration of first dose 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 can be noted at any time prior to randomization but within 10 days of potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that was 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
• Total white blood cell (WBC) count > 2,500/ul (not older than 48 hours at the time of randomization)
• Absolute neutrophil count (ANC) > 1,500/uL (not older than 48 hours at the time of randomization)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 20 times the upper limit of the institutional normal ranges (not older than 48 hours at the time of randomization)
• 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
• Must be willing and able to abide by all study requirements and restrictions

Exclusion Criteria

• 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 months) exposure to abatacept or belatacept
• Concurrent or recent (=< 2 months) use of the following non-corticosteroid immunosuppressive therapies: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, intravenous immunoglobulin, infliximab, and plasma exchange
• 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