Abatacept for Myocarditis
(ATRIUM Trial)
Recruiting in Palo Alto (17 mi)
+31 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This Trial tests if abatacept can reduce serious heart problems in patients with heart inflammation caused by cancer treatments. Abatacept calms the immune system by preventing certain immune cells from becoming fully active, reducing inflammation and damage. Abatacept has been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, with or without methotrexate.
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.
What data supports the effectiveness of the drug abatacept for myocarditis?
Abatacept has been shown to be effective in reducing inflammation and pain in conditions like rheumatoid arthritis by interfering with T cell activation, which is a part of the immune response. This suggests it might help with myocarditis, which also involves inflammation.
12345Is abatacept generally safe for humans?
Abatacept (Orencia) has been studied for safety in people with rheumatoid arthritis, showing that it can cause infections and allergic reactions. Patient alert cards are used to inform patients and healthcare professionals about these risks.
13456How is the drug abatacept unique for treating myocarditis?
Abatacept is unique for treating myocarditis because it targets T cell activation, which is a different approach compared to standard treatments that often focus on reducing inflammation with steroids. It works by blocking a specific signal needed for T cells to become active, potentially reducing heart inflammation and damage.
16789Eligibility Criteria
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.
+8 more
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.
+7 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Abatacept plus standard of careExperimental Treatment1 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 carePlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cleveland ClinicCleveland, OH
MD Anderson Cancer CenterHouston, TX
Columbia University Irving Medical CenterNew York, NY
Franciscan HealthIndianapolis, IN
More Trial Locations
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
Bristol-Myers SquibbIndustry Sponsor
References
Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023]Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a co-stimulatory signal necessary for T cell activation. We aimed to analyse the efficacy and safety of abatacept in the management of rheumatoid arthritis using the Cochrane systematic review.
Abatacept for rheumatoid arthritis. [2021]Abatacept inhibits the co-stimulation of T cells and disrupts the inflammatory chain of events that leads to joint inflammation, pain, and damage in rheumatoid arthritis.
A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. [2022]To compare the efficacy of abatacept to that of placebo for the treatment of giant cell arteritis (GCA).
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. [2023]We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.
New pharmacological strategies in rheumatic diseases. [2022]Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.
Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. [2021]Patient alert cards (PACs) for abatacept (ORENCIA) inform patients and healthcare professionals (HCPs) about the risk of infections and allergic reactions. The study evaluates the effectiveness of the PACs in rheumatoid arthritis patients and HCPs, using process indicators (awareness, receipt, utility, knowledge, behaviour) and outcomes.
Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept. [2022]Immune-checkpoint inhibitors (ICI) have revolutionized cancer therapy but are associated with infrequent but lethal myocarditis, for which management remains uncertain. Abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells and leading to global T-cell anergy, has been described as a potential treatment in individual reports. Yet, abatacept treatment dosage, schedule and optimal combination with other immunosuppressive therapies are unclear. We describe a 25-year-old man who developed pembrolizumab (anti-PD1)-induced myocarditis 14 days after first injection for thymoma treatment, which deteriorated into cardiogenic shock, with sustained ventricular arrhythmia, requiring urgent extracorporeal life support implantation, despite prompt initiation of corticosteroids and mycophenolate-mofetil. Using a strategy of serial measurement ensuring with a target of >80% CD86 receptor occupancy on circulating monocytes, abatacept dose was adjusted and combined with ruxolitinib and methylprednisolone. This strategy resulted in high-dose of abatacept: 60 mg/kg in three doses (20 mg/kg each) within the first 10 days, followed by two doses. Clinical improvement occurred within 7 days, with resolution of systolic cardiac dysfunction, and ventricular arrhythmias resulting in successful discharge from hospital. We reversed a case of nearly lethal ICI-myocarditis, using specific patient-dose adjusted abatacept, which may serve as basis for personalized treatment of patients with severe ICI-adverse events. Trial registration number: NCT04294771.
T cell costimulation blockade blunts pressure overload-induced heart failure. [2018]Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. [2018]To compare the efficacy of abatacept to that of placebo for the treatment of Takayasu arteritis (TAK).