Abatacept for Myocarditis

(ATRIUM Trial)

Recruiting at 32 trial locations

Overseen By Hannah K Gilman, MS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Massachusetts General Hospital

Must be taking: Solumedrol

Must not be taking: Abatacept, Belatacept, JAK inhibitors

Disqualifiers: Active infections, Pregnancy, Recent cardiac events, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

390 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if abatacept, a medication, can reduce serious heart problems in people hospitalized with myocarditis (heart inflammation) linked to immune checkpoint inhibitors (a type of cancer treatment). Participants will receive either abatacept (also known as Orencia, an immunosuppressant drug) or a placebo alongside standard care to assess which group experiences better heart health outcomes. This trial suits individuals hospitalized with myocarditis after recent cancer treatment with an immune checkpoint inhibitor and who are currently on or about to start high-dose steroids for their heart condition. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have recently used certain immunosuppressive therapies like mycophenolate or JAK STAT inhibitors. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that abatacept is likely to be safe for humans?

Research has shown that abatacept is generally well-tolerated by patients. The FDA has already approved it for treating other conditions, such as rheumatoid arthritis, indicating a good safety record. Some studies suggest that while heart inflammation can be a serious side effect of certain cancer treatments, abatacept might help manage this issue. No major safety concerns have been specifically linked to abatacept in these situations, but it's important to remember that reactions can vary. As always, discuss any side effects with your doctor when considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myocarditis?

Unlike the standard treatments for myocarditis, which typically involve medications like corticosteroids or heart failure drugs, Abatacept offers a unique approach by targeting the immune system more precisely. Abatacept is a biologic that interferes with the T-cell activation process, potentially reducing inflammation more effectively. Researchers are excited because this mechanism could lead to more targeted control of the immune response, possibly improving outcomes for patients with myocarditis faster and with fewer side effects compared to traditional treatments.

What evidence suggests that abatacept might be an effective treatment for myocarditis?

Research has shown that abatacept might help reduce heart problems in patients with myocarditis caused by immune checkpoint inhibitors (ICI). In animal studies, abatacept decreased heart inflammation and improved heart health. Current treatments, such as steroids, have not been very effective, and death rates remain high. In this trial, some participants will receive abatacept, which calms the immune system's overreaction, believed to cause this heart inflammation. Early results suggest that abatacept might lower the risk of serious heart issues, offering hope for better outcomes. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults hospitalized with myocarditis caused by recent immune checkpoint inhibitor therapy for cancer, who are on or starting high-dose corticosteroids. Participants must have certain blood cell counts within normal ranges, not be pregnant or breastfeeding, and agree to use contraception. Exclusions include active infections like TB, recent live vaccines, other immunosuppressive treatments, and participation in another interventional study.

Inclusion Criteria

I am currently in the hospital.

My heart test shows damage more than 5 times the normal limit recently.

I have been diagnosed with myocarditis.

Exclusion Criteria

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

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

I haven't had major heart issues or used specific drugs in the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either abatacept or placebo, administered IV after randomization, again at 24 hours, at 14 days, and an optional 4th dose at 28 days

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary and secondary outcomes measured over 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Placebo

Trial Overview The trial is testing if abatacept can reduce major cardiac events compared to a placebo in patients with myocarditis following cancer treatment with immune checkpoint inhibitors. The main outcome measures include cardiovascular death and various heart-related complications.

How Is the Trial Designed?

Group I: Abatacept plus standard of care Experimental Treatment 1 Intervention

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 II: Placebo plus standard of care Placebo Group 1 Intervention

Placebo will be administered at the same intervals.

Abatacept is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

This study protocol outlines a 52-week trial involving 206 participants to evaluate the effectiveness of abatacept, a co-stimulatory blocker, in preventing or delaying inflammatory arthritis in individuals at risk for rheumatoid arthritis (RA).

The trial is designed to rigorously assess the time to develop significant joint swelling, with all participants and assessors blinded to treatment assignments, ensuring unbiased results in determining the efficacy of abatacept compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol. Al-Laith, M., Jasenecova, M., Abraham, S., et al.[2023]

In a multicenter trial involving 49 patients with giant cell arteritis (GCA), the addition of abatacept to a prednisone regimen significantly improved relapse-free survival rates at 12 months (48% for abatacept vs. 31% for placebo).

Patients receiving abatacept also experienced a longer median duration of remission (9.9 months) compared to those on placebo (3.9 months), with no increase in adverse events, indicating that abatacept is both effective and safe for treating GCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2022]

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

Abatacept significantly improves disease activity and physical function in patients with moderate to severe rheumatoid arthritis, with a 2.2 times higher likelihood of achieving an ACR 50 response compared to placebo, based on a review of 7 trials involving 2908 patients.

While abatacept is generally safe, it is associated with a higher risk of serious infections and should not be used in combination with other biologics due to increased serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept for rheumatoid arthritis. Maxwell, L., Singh, JA.[2021]

Abatacept is a novel treatment that inhibits T-cell activation, effectively normalizing the immune response in patients with rheumatic diseases, and has been approved as a second-line biologic treatment for rheumatoid arthritis in Romania.

Clinical studies have demonstrated the efficacy of abatacept in reducing disease activity and improving quality of life in various rheumatic diseases, while also highlighting its favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New pharmacological strategies in rheumatic diseases. Schiotis, RE., Buzoianu, AD., Mureșanu, DF., et al.[2022]

The study found that 60% of rheumatoid arthritis patients were aware of the patient alert cards (PACs) for abatacept, and those who received the PACs had significantly better knowledge about the risk of infections compared to those who did not (64% vs 46%).

Among healthcare professionals, 90% were aware of the PACs, and those who accessed the cards had a higher understanding of infection risks (91% vs 73%), indicating that PACs effectively enhance safety knowledge for both patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. Artime, E., Kahlon, R., Méndez, I., et al.[2021]

In a multicenter trial involving 34 patients with Takayasu arteritis, the addition of abatacept to prednisone treatment did not significantly improve relapse-free survival compared to placebo, with rates of 22% for abatacept and 40% for placebo at 12 months.

There were no significant differences in the frequency or severity of adverse events, including infections, between the abatacept and placebo groups, indicating that abatacept is safe but ineffective in prolonging remission in Takayasu arteritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Langford, CA., Cuthbertson, D., Ytterberg, SR., et al.[2018]

In a mouse model of heart failure, the FDA-approved drug abatacept, which blocks T cell costimulation, significantly delayed the progression and reduced the severity of cardiac dysfunction by inhibiting T cell and macrophage activation.

The therapeutic effects of abatacept were linked to increased production of the anti-inflammatory cytokine interleukin-10 (IL-10), suggesting that enhancing IL-10 levels is crucial for its protective effects against heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell costimulation blockade blunts pressure overload-induced heart failure. Kallikourdis, M., Martini, E., Carullo, P., et al.[2018]

A 25-year-old man developed severe myocarditis after receiving pembrolizumab for thymoma, leading to cardiogenic shock, but showed significant clinical improvement after a personalized treatment regimen with high-dose abatacept, combined with ruxolitinib and methylprednisolone.

This case suggests that adjusting abatacept dosage based on CD86 receptor occupancy may provide an effective strategy for managing severe immune-checkpoint inhibitor-related myocarditis, potentially guiding future personalized treatments for similar adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept. Nguyen, LS., Bretagne, M., Arrondeau, J., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS2680

Abatacept for immune checkpoint inhibitor associated ... In preclinical animal models of ICI myocarditis, the administration of abatacept led to a reduction in cardiac immune activation and an increase ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1875213624006946

Abatacept dose-finding phase II triaL for immune ... In ICI myocarditis, available therapeutics produced poor results and mortality has stagnated (25–50%) in the last decade despite widespread glucocorticoids use ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05195645

NCT05195645 | AbataCept for the Treatment of Immune- ... Among those irAEs, ICI-induced myocarditis was the most frequently fatal with death rate reaching 50% in a large case-series of over 100 patients. This study is ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9830216/

Immune Checkpoint Inhibitor Myocarditis Treatment ... In this case, the abatacept dose used in the first 2 weeks was 4 to 6 times higher compared with those expected to be used in already approved ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMc1901677

Abatacept for Severe Immune Checkpoint Inhibitor– ... Autoimmune myocarditis is a rare but often fatal complication of immune checkpoint inhibitor therapy for cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05335928

Abatacept in Immune Checkpoint Inhibitor Myocarditis The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11903268/

Immune checkpoint Inhibitor related myocarditis reported ... Myocarditis continues to be associated with immune checkpoint inhibitors, with the number of reported cases increasing consistent with increasing utilization.