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Myocarditis AcutePhase 3ATRIUMNCT05335928

Abatacept in Immune Checkpoint Inhibitor Myocarditis

A Phase 3 study testing Abatacept plus in people with Myocarditis Acute and Cancer, run by Massachusetts General Hospital at 31 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myocarditis Acute, Cancer
What is being tested?
Abatacept plus
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
390 participants
Where
31 sitesin 2 countries
Study dates
2 Jul 2022to 9 Oct 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

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

  • 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;
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

31 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Hannah K Gilman, MS contact

6177261019

hkgilman@mgh.harvard.edu

31 sites in 2 countries

United States29 sites, 29 recruiting

  • University of Michigan

    Ann Arbor, Michigan, 48109

    Salim Hayek, MD, shayek@med.umich.edu

    Salim Hayek, MD

    Recruiting

  • Johns Hopkins

    Baltimore, Maryland, 21287

    Joban Vaishnav

    Joban Vaishnav

    Recruiting

  • Lehigh Valley Health Network

    Bethlehem, Pennsylvania, 18017

    Nicholas Trask

    Deborah Sundlof

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Daniel Zlotoff, MD, PhD, 6177262000, dzlotoff@mgh.harvard.edu

    Kerry Reynolds, MD

    Recruiting

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

    Abul Aritizia, MD

    Aarti Asnani, MD

    Recruiting

  • Boston Medical Center

    Boston, Massachusetts, 02118

    Omar Siddiqi

    Omar Siddiqi, MD

    Recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

    Anju Nohria, MD, ANOHRIA@PARTNERS.ORG

    Anju Nohria, MD

    Recruiting

  • University of North Carolina Chapel Hill

    Chapel Hill, North Carolina, 27599-7075

    Brian Jensen, MD

    Brian Jensen, MD

    Recruiting

  • University of Chicago

    Chicago, Illinois, 60637

    Jeanne DeCara

    Jeanne DeCara

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Rohit Moudgil

    Rohit Moudgil

    Recruiting

  • University of Texas Southwestern

    Dallas, Texas, 72535

    Saketh Nadimpalli, Saketh.Nadimpalli@UTSouthwestern.edu

    Vlad Zaha, MD

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Nicolas Palaskas, NLPalaskas@mdanderson.org

    Nicolas Palaskas, MD

    Not yet recruiting

  • Franciscan Health

    Indianapolis, Indiana, 46237

    Ryan Daly

    Ryan Daly, MD

    Recruiting

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

    Charles Porter

    Charles Porter, MD

    Recruiting

  • University of Kentucky

    Lexington, Kentucky, 40536-0200

    Amit Arbune

    Amit Arbune, MD

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 02127

    Kiranbir Josan, MD

    Kiranbir Josan, MD

    Recruiting

  • University of California Los Angeles

    Los Angeles, California, 90095

    Eric Yang, MD

    Eric Yang, MD

    Recruiting

  • Aurora St Luke's Medical Center

    Milwaukee, Wisconsin, 53215

    Manmeet Singh

    Manmeet Singh

    Recruiting

  • University of West Virginia

    Morgantown, West Virginia, 26506

    Brijesh Patel

    Brijesh Patel, MD

    Recruiting

  • Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08901

    Amna Zafar

    Amna Zafar

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Jayant Raikhelkar

    Jayant Raikhelkar

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Dipti Gupta, MD

    Dipti Gupta, MD

    Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Michael Fradley

    Michael Fradley

    Recruiting

  • Allegheny-Singer Research Institution

    Pittsburgh, Pennsylvania, 15212

    Valentyna Ivanova

    Ivanova Ivanova, MD

    Recruiting

  • Maine Health

    Portland, Maine, 04102

    Maxwell Afari

    Maxwell Afari, MD

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Joerg Herrmann

    Joerg Herrmann, MD

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84132

    Anees Daud, MD

    Anees Daud, MD

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Mohammed v

    Mohammed Alomar

    Recruiting

  • MedStar Health Research Institute, Georgetown University

    Washington D.C., District of Columbia, 20010

    Hayder Hashim

    Hayder Hashim

    Recruiting

Other trials in United States

Canada2 sites, 2 recruiting

  • McMaster University

    Hamilton, Ontario, L8V 1C3

    Darryl Leong

    Darryl Leong, MD

    Recruiting

  • University of British Colombia

    Vancouver, British Colombia, V5Z 1M9

    Margot Davis

    Margot Davis, MD

    Recruiting

Other trials in Canada

About this study

Official title: AbatacepT foR ImmUne Checkpoint Inhibitor Associated Myocarditis (ATRIUM): A Phase 3, Investigator-Initiated, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept in ICI Myocarditis

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.

Read the detailed description

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

Being tested
Abatacept plus, Placebo
Keywords
Immune checkpoint Inhibitor, Myocarditis, Abatacept, Immune therapy, Immune related adverse events
Medical subject headings
Neoplasms, Myocarditis

What participants receive

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

  • Abatacept plusDrug

    Also called Orencia

    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

  • PlaceboDrug

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

Study groups in NCT05335928
Study groupRoleWhat they receive
Abatacept plus standard of careExperimentalAbatacept (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.
Receives: Drug: Abatacept plus
Placebo plus standard of carePlacebo comparatorPlacebo will be administered at the same intervals.
Receives: Drug: Placebo

What is being measured

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

  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.

    Measured: 6 months

Secondary outcomes (8)

  1. The individual components of the primary endpoint.

    The rates of the following between groups: cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmias, significant bradyarrhythmias, or incident heart failure

    Measured: 6 months

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

    The worst score on a 7-point ordinal myocarditis severity scale during the 6 month period from first study treatment. The 7-point ordinal myocarditis severity scale is as follows with more severe outcomes ranked with a higher number:

    1. - No component of the primary endpoint;
    2. - Incident heart failure;
    3. - Significant bradyarrhythmia;
    4. - Significant ventricular tachyarrhythmias;
    5. - Cardiogenic shock;
    6. - Sudden cardiac arrest;
    7. - Cardiovascular death;

    Measured: 6 months

  3. The increase in serum troponin levels

    The proportion of participants in each group with a >50% increase in serum troponin value at any time during the incident hospitalization and following administration of study drug.

    Measured: 6 months

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

    The rates of a composite of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrhythmias, significant bradyarrhythmias, or incident heart failure plus the proportion of participants in each group with a >50% increase in serum troponin value at any time during the incident hospitalization and following administration of study drug.

    Measured: 6 months

  5. Clinical status at 90 days after first infusion of study drug

    Clinical status at visit 6 (day 90) on an ordinal scale with highest being the worst:

    1. - Alive and off corticosteroids for myocarditis;
    2. - Alive and on corticosteroids (provide dose) for myocarditis;
    3. - Alive and on cellcept (provide dose) for myocarditis;
    4. - Alive and on both corticosteroids (provide dose) and cellcept (provide dose) for myocarditis
    5. - Dead (cancer, cardiovascular or other).

    Measured: 6 months

  6. Clinical status at 6 months after first infusion of study drug

    Clinical status at visit 7 (6 months) with the highest being the worst:

    1. - Alive and off corticosteroids for myocarditis;
    2. - Alive and on corticosteroids (provide dose) for myocarditis;
    3. - Alive and on cellcept (provide dose) for myocarditis;
    4. - Alive and on both corticosteroids (provide dose) and cellcept (provide dose) for myocarditis
    5. - Dead (cancer, cardiovascular or other).

    Measured: 6 months

  7. Fatal and non-fatal DVT and PE

    The proportion of patients in each group with a fatal and non-fatal DVT and PE will be compared.

    Measured: 6 months

  8. Other immune-related adverse events between the two groups

    Rates of other immune-related adverse events between the two groups will be compared.

    Measured: 6 months

Timeline

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

  1. First posted20 Apr 2022
  2. Study start2 Jul 2022
  3. Primary completion9 Apr 2029 (estimated)
  4. Study completion9 Oct 2029 (estimated)

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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
390 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05335928
Sponsor's protocol ID
2021P003690
Acronym
ATRIUM
Status last verified
Aug 2026
First submitted
5 Apr 2022
Last updated
20 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38963866

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Abatacept plus in people with Myocarditis Acute and Cancer, run by Massachusetts General Hospital at 31 sites in 2 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 13 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Hannah K Gilman, MS (6177261019, hkgilman@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major adverse cardiac events (time frame: 6 months). 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 NCT05335928, which also lists 1 linked publication.

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 20 Aug 2026.

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