MyocarditisPhase 2ACHLYSNCT05195645

AbataCept for the Treatment of Immune-cHeckpoint Inhibitors Induced mYocarditiS

A Phase 2 study testing Abatacept 250 MG in people with Myocarditis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Myocarditis
What is being tested?: Abatacept 250 MG
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteFrance
Study dates: 27 Oct 2022to 28 Jan 2025
Phase: Phase 2
Are there results?: None posted in the registry

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

Age ≥ 18 years old
Weight ≥ 40 kg and ≤ 125 kg
Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer (even those in which ICI is not currently approved by regulatory)
Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations (e.g27, to be updated with any new recommendations to be published)
Severe or corticosteroid-resistant ICI-myocarditis:
Severe ICI-myocarditis is defined either 1/ by the appearance of an alteration of the LVEF<50% or a wall motion kinetics abnormality, or 2/ by the appearance of ventricular tachycardias or high-grade conductive disorders (atrioventricular block grade 2 or 3) or 3/ by the association with myasthenia gravis-like-syndrome (diplopia, ptosis, diaphragmatic dysfunction, dysarthria, dysphonia, dysphagia) or 4/ by troponin-T levels above 32 times the upper limit of the normal (a population at very high-risk ~75% of major cardiomuscular events in the month following initial presentation, cf. Circulation. 2023 Aug 8;148(6):473-486).

Show all 10Show fewer

Corticosteroid-resistant ICI-myocarditis is defined by the absence of decrease in troponin levels or the appearance/persistence of severity criteria despite receiving prednisone dose ≥0.5 mg/kg/day for ≥2 days.
Signature of informed consent before any trial procedure from the patient or legal representative or the close relative
Patients covered by social security regimen (excepting AME)
Withhold of ICI

Who cannot join

Untreated and/or uncontrolled bacterial, fungal, or viral infection
Pregnancy, breast-feeding or planning to become pregnant during the study period
For women of childbearing age, lack of effective contraception throughout the duration of participation in the study
Being treated with abatacept or belatacept within 3 months prior to inclusion
Known hypersensitivity to abatacept or belatacept
Being treated with anti-thymoglobulin, or alemtuzumab within 6 weeks of the first scheduled dose of abatacept
Patient participating to another interventional study (RIPH 1 only)
People under legal protection measure (tutorship, curatorship or safeguard measures)

Trial locations and contacts

1 site in 1 country.

France1 site

Hôpital Pitié Salpêtrière
Paris, 75013

Other trials in France

About this study

This study is a dose-finding Phase II trial where 3 abatacept IV regimen (A-10 mg/kg; B-20 mg/kg and C-25 mg/kg at Day0, Day5+/-2, Day14+/-2) will be tested aiming at reaching promptly (after the first dose) and sustainably a CD86RO≥80% during the first 3 weeks of ICI-myocarditis management. The main objective is to find the lowest dose required to achieve a circulating monocytes CD86RO≥80% within the first week of treatment and sustainably over three weeks. The target population is all adult patients with cancer (all cancer types) treated by immune checkpoint inhibitors (anti-PD1, anti-PDL1, anti-CTLA4 monotherapies or combination) and presenting drug-induced myocarditis.

Read the detailed description

Immune-checkpoint-inhibitors (ICI) have revolutionized treatment for about 20 cancer types. They unleash anti-tumor immune responses. Unfortunately, in 0.36-1.23% of patients, this activation can also lead to lethal immune-related adverse events (irAEs) that can affect any organ. 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. Other severe irAEs are pneumonitis, hepatitis and neuromyotoxicities (myositis, myasthenia gravis-like syndrome) with death rates of 20-25%. Co-occurrence of irAEs affecting multiple organs is frequent (30% for myocarditis and myositis) as they share underlying mechanisms with macrophages and cytotoxic T-cell infiltrates leading to organ destruction.

While rigorous studies for the treatment of irAEs are lacking, consensus guidelines recommend treatment with high-dose corticosteroids with progressive tapering and withholding ICI. When symptoms and biological markers do not improve, other immunosuppressive drugs (mycophenolate-mofetil, methotrexate, cyclosporine, cyclophosphamide, azathioprine, antithymocyte globulin, infliximab, tocilizumab, and rituximab) can be considered, depending on organs affected. Intravenous immunoglobulin or plasmapheresis can also be considered. In patients developing myocarditis, available therapeutics produce poor results and the fatality rate (40-50%) has stagnated between 2014-2019 despite increasing glucocorticoids use. No treatment has been shown to improve this situation. Thus, better reversal agents' strategies are urgently needed in the context of the increasing use of ICI and of associated irAEs. Abatacept and belatacept (CTLA4-immunoglobulin fusion proteins) have very promising properties: they inhibit CD80/CD86 mediated T-cell co-stimulation at the level of dendritic-cells, thereby abrogating activation of the T-cells upstream of the CTLA4 and PD1/PDL1 pathways. "CTLA4 agonists" leads to global T-cell anergy with limited off-target effects, and specifically reverse ICI-activated pathways.

Abatacept is currently indicated in rheumatological disorders such as rheumatoid arthritis and belatacept is indicated in kidney rejection transplantation prophylaxis. In these latter indications, the circulating monocytes CD86 receptor occupancy (CD86RO) by "CTLA4 agonists" is a relevant pharmacodynamic biomarker of their clinical activity. The target CD86RO cut-off should be over 80%.

Confirming the rationale for "CTLA4 agonists" use in ICI-myocarditis, the investigators recently showed that abatacept was able to alleviate fatal myocarditis in CTLA4/PD1 genetic knock-out mice model. Finally, this group recently described the first cases of glucocorticoid-refractory myocarditis induced by nivolumab (anti-PD1) which resolved after treatment with abatacept. This success prompted the investigators to treat over 15 ICI-myocarditis patients in their institution and several other teams to use abatacept in ICI-induced myocarditis with encouraging results. Though, in their experience, initial doses of abatacept needed to promptly reach CD86RO≥80% in ICI-myocarditis setting were much higher than those needed in its usual indications. Due to abatacept slow time to onset, combination with ruxolitinib (a JAK inhibitor) on top of corticosteroids was also proposed in ICI myocarditis management with very promising results (ICI-myotoxicity related mortality dropped from 60% on corticosteroids + 2nd line abatacept to 3% in 1st line abatacept + ruxolitinib + corticosteroids (https://doi.org/10.1158/2159-8290.CD-22-1180).

Abatacept will be added to the standard of care of these severe ICI myocarditis patients, which include preferentially prednisone and ruxolitinib, tapered as a function of the bio-clinical evolution of ICI-myocarditis.

Conditions: Myocarditis
Being tested: Abatacept 250 MG
Keywords: Myocarditis, Immune-checkpoint-inhibitors (ICI), ICI-induced myocarditis, immune-related adverse events, Abatacept, Dose-finding
Medical subject headings: Myocarditis

What participants receive

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

Abatacept 250 MGDrug
Also called ORENCIA® BMS
Abatacept will be administered by intravenous injection over 1h15 to 2h30 on D1, D5+/-2 and D14+/-2 at 10mg/kg (arm A), or 20mg/kg (arm B) or 25mg/kg (arm C) depending on the randomization (max 3 000 mg per administration). Starting Day 21 (after evaluation of the primary outcome), other injection of abatacept may be given (D22 at D90) with dosage (10 or 20mg/kg max) decided by the treating physician (max 2 500 mg per administration) as a function of the relapse or not of the ICI myocarditis after immunosuppressant therapeutics tapering. After day 21, the administrations will be carried out in open but the blind administration 1 to 3 (D1 to D21) will be kept.

Study groups in NCT05195645
Study group	Role	What they receive
A-10mg/kg	Experimental	Patients in arm A will receive doses of 10 mg/kg of Abatacept Receives: Drug: Abatacept 250 MG
B-20mg/kg	Experimental	Patients in arm B will receive doses of 20 mg/kg of Abatacept Receives: Drug: Abatacept 250 MG
C-25mg/kg	Experimental	Patients in arm C will receive doses of 25 mg/kg of Abatacept Receives: Drug: Abatacept 250 MG

What is being measured

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

Proportion of patients with an adequate circulating monocytes CD86 receptor occupancy (CD86RO) saturation ≥ 80%
A patient will be considered with an adequate CD86RO saturation (≥80%) within the first weeks of treatment if at least three CD86RO assessment are over 80% until Day 21 after the first abatacept administration.
Measured: CD86RO will be assessed versus baseline levels (1 to 3 hours before 1st abatacept administration for baseline) and then, once 1 to 3 hours and 12 to 72 hours after the 1st, 2nd and 3rd abatacept administration, and at Day 21 .

Secondary outcomes (52)

Quantification of proxies reflecting the resolution of systemic immune activation
% of regulator T-cells CTLA4+ will be assessed versus baseline levels (one to 3 hours before abatacept treatment, preferentially before corticosteroids or any other immunossupressant intake). In case of additional doses of abatacept, it will also be additionally measured one to 3 hours before and one to three hours after each dose of abatacept.
Measured: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Levels of pro and anti-inflammatory cytokines will be assessed versus baseline levels (one to 3 hours before abatacept treatment, preferentially before corticosteroids or any other immunossupressant intake). In case of additional doses of abatacept, it will also be additionally measured one to 3 hours before and one to three hours after each dose of abatacept.
Measured: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
C-reactive protein levels will be assessed versus baseline levels (one to 3 hours before abatacept treatment, preferentially before corticosteroids or any other immunossupressant intake). In case of additional doses of abatacept, it will also be additionally measured one to 3 hours before and one to three hours after each dose of abatacept.
Measured: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
% of circulating T-cells expressing PDL1 will be assessed versus baseline levels (one to 3 hours before abatacept treatment, preferentially before corticosteroids or any other immunossupressant intake). In case of additional doses of abatacept, it will also be additionally measured one to 3 hours before and one to three hours after each dose of abatacept.
Measured: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
% of circulating T-cells expressing PD1 will be assessed versus baseline levels (one to 3 hours before abatacept treatment, preferentially before corticosteroids or any other immunossupressant intake). In case of additional doses of abatacept, it will also be additionally measured one to 3 hours before and one to three hours after each dose of abatacept.
Measured: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the corticosteroid decrease kinetics (total cumulative dose)
Measured: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the corticosteroid decrease kinetics (total cumulative dose)
Measured: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the corticosteroid decrease kinetics (time to weaning)
Measured: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the corticosteroid decrease kinetics (time to weaning)
Measured: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the proportion of patients for whom it was necessary to add other immunosuppressants in addition to glucocorticoids to control the disease
Measured: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Quantification of the proportion of patients for whom it was necessary to add other immunosuppressants in addition to glucocorticoids to control the disease
Measured: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Cumulative dose of other immunosuppressants added to glucocorticoids in patients for whom it was necessary to add this immunossupressant to control the disease
Measured: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Cumulative dose of other immunosuppressants added to glucocorticoids in patients for whom it was necessary to add this immunossupressant to control the disease
Measured: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Time to weaning of other immunosuppressants added to glucocorticoids in patients for whom it was necessary to add this immunossupressant to control the disease
Measured: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time to weaning of other immunosuppressants added to glucocorticoids in patients for whom it was necessary to add this immunossupressant to control the disease
Measured: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of myocarditis
Incidence of heart failure (defined as left-ventricular drop below 50%)
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Incidence of life-threatening cardiac arrhythmias (defined a sustained >30 seconds ventricular tachycardia epidose, ventricular fibrillation, cardiac arrest, sinus arrest >4 seconds and complete atrio-ventricular block).
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Evolution of grading of the cardiomyotoxicity overall
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Evolution of grading of the cardiomyotoxic sub-features (cardiac dysfunction)
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Evolution of grading of the cardiomyotoxic sub-features (cardiac pro-arrhythmias)
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Evolution of grading of the cardiomyotoxic sub-features (respiratory muscle dysfunction)
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Evolution of grading of the cardiomyotoxic sub-features (dysphagia)
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
troponin-T and -I maximal value
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Area under the curve of troponin levels
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Area under the curve of Creatine Kinase level
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Creatine Kinase level maximal value
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
NT-proBNP maximal value
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Area under the curve of NT-proBNP
Measured: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
left ventricular ejection fraction by echocardiography
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the resolution of myocarditis
Cardiac inflammation and myocardial edema quantification by cardiac MRI
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the resolution of myocarditis
Arrhythmias and ventricular conductive disorders quantified on 48hours electrocardiographic Holter acquisitions
Measured: At admission, Day 5, Day 14, Day 21, Day 90 and then every 3 months up to one year
Quantification of proxies reflecting the resolution of myocarditis
Humoral autoimmunity against the myocardium or the muscles (anti- cardiac troponin I and T, anti-titin, anti-muscle specific kinases (musK), anti-acetylcholine receptor antibodies).
Measured: At admission, Day 21, Day 90, 6 months and one year
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Presence/absence on electromyogram assessment of : myogenic syndrome (0/1), diaphragmatic nerve dysfunction (0/1), decrement on assessment of neuromuscular dysfunction (0/1)
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis:
Number of significant hypoxemic episodes by capnography
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Proportion of time with abnormal CO2 (%) by capnography.
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Maximum C02 (mmHg) by capnography
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Presence/absence of restrictive syndrome (0/1) by functional respiratory exploration.
Presence/absence of sign of diaphragmatic failure (0/1) by functional respiratory exploration.
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Maximal/minimal Inspiratory Pressure (mmHg) by functional respiratory exploration.
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis:
Excursion of the right and left diaphragmatic border (mm) by diaphragmatic MRI and echography
Measured: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of the volume of distribution (Liter) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of the terminal half-life (days) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of clearance (ml/min/kg) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of maximum concentration of circulating abatacept (Cmax, µg/ml) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of residual concentration of circulating abatacept (Cmin, µg/ml) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Determination of time to Cmax (hours) by using all the evaluated abatacept circulating levels
Measured: Throughout the study completion (up to one year after randomization)
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Modelling of the 50% median effective concentration (µg/ml) of abatacept to saturate CD86 receptor on circulating monocytes (%) and to achieve troponin safety levels targets
Measured: Abatacept, CD86RO and troponin-T blood levels assessed minimum at baseline (1-3h before abatacept) and once 1-3h after, and 12-72h after 1st, 2nd, 3rd and extra abatacept doses, then every 10days up to day90, and then every 3months up to 1year.
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Presence of Abatacept anti-drug antibody (ADA, 0/1)
Measured: ADA will be searched at inclusion (before 1st abatacept intake), and then at day 21, 3 months and 6 months after randomization
Quantification of tumor progression
Quantification of tumor progression by appropriate examination depending on the tumor type (e.g. CT-scan for lung or renal cancer) using the best monitoring work-up used in standard of care.
Measured: The imaging modalities will be assessed at least once as soon as possible after admission, after 3 months and one year after abatacept start.
Quantification of tumor progression
Progression free survival defined as time from randomization to progression according to RECIST criteria
Measured: Progression free survival rate at 90days, 6 months and 12 months
Quantification of the number and severity (in particular fatal) of adverse events, in particular infectious, according to the CTCAE v5.0 classification.
A Full clinical examination searching for any ongoing infection before starting treatment and active clinical monitoring of any sign of new infection during the treatment course and for 1 year.
The biological monitoring will include with a blood PCR seeking for CMV reactivation weekly for 4 weeks and then at 3 months and one year (in patients carrying a positive serology for CMV); as well as a blood next generation sequencing seeking for pathogens will be assessed at least once as soon as possible after admission, then at day 14, 3 months and one year after the first abatacept administration.
Measured: Full clinical examination : Before starting treatment, during the treatment course and during 1 year / Active clinical monitoring during the treatment course and for 1 year / Biological monitoring : During the first 4 weeks, at 3 months and one year
Overall survival
Proportion of patients alive without myotoxicity grade >2
Measured: Between Day 0 and 1 month, 3 months, 6 months and 12 months
Overall survival
Proportion of patients alive
Measured: Between Day 0, and 3 months, 6 months and 12 months

Timeline

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

27 Oct 202228 Jan 2025

First posted19 Jan 2022
Study start27 Oct 2022
Primary completion5 Mar 2024
Study completion28 Jan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for MyocarditisStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05195645
Sponsor's protocol ID: APHP210303
Acronym: ACHLYS
Status last verified: Jul 2026
First submitted: 10 Dec 2021
Last updated: 16 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

Publications

Salem JE, Ederhy S, Belin L, Zahr N, Tubach F, Procureur A, Allenbach Y, Rosenzwjag M, Bretagne M. Abatacept dose-finding phase II triaL for immune checkpoint inhibitors myocarditis (ACHLYS) trial design. Arch Cardiovasc Dis. 2025 Feb;118(2):106-115. doi: 10.1016/j.acvd.2024.12.005. Epub 2024 Dec 20.
PubMed 39743436

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Baduanjin Rehabilitation for Functional Restoration in ICI-Associated Myocarditis
Immune Checkpoint Inhibitors Related Myocarditis
Not yet recruitingObservational study
Monitoring and Rehabilitation for ICIACI Rehabilitation：A Cohort Study
Immune Checkpoint Inhibitor-Related Myocarditis
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
Recruiting
Heart@Home Safety and Efficacy of Hospital-at-Home Care Versus Standard Hospitalization in Cardiac Patients
Myocardial Infarction, Myocarditis Acute
RecruitingObservational study
MYocarditis and/or Pericarditis Following mRNA COVID-19 VACCination National Surveillance Study
Myocarditis, Myocarditis Acute

All Myocarditis trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: AbataCept for the Treatment of Immune-cHeckpoint Inhibitors Induced mYocarditiS
ClinicalTrials.gov ID: NCT05195645
Acronym / sponsor ID: ACHLYS / APHP210303
Conditions: Myocarditis
Keywords: Myocarditis, Immune-checkpoint-inhibitors (ICI), ICI-induced myocarditis, immune-related adverse events, Abatacept, Dose-finding
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Study start: 27 Oct 2022 (actual)
Primary completion: 5 Mar 2024 (actual)
Study completion: 28 Jan 2025 (actual)
First posted: 19 Jan 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
A-10mg/kg	Experimental	Drug: Abatacept 250 MGPatients in arm A will receive doses of 10 mg/kg of Abatacept
B-20mg/kg	Experimental	Drug: Abatacept 250 MGPatients in arm B will receive doses of 20 mg/kg of Abatacept
C-25mg/kg	Experimental	Drug: Abatacept 250 MGPatients in arm C will receive doses of 25 mg/kg of Abatacept

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Age ≥ 18 years old
Weight ≥ 40 kg and ≤ 125 kg
Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer (even those in which ICI is not currently approved by regulatory)
Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations (e.g27, to be updated with any new recommendations to be published)
Severe or corticosteroid-resistant ICI-myocarditis:

Key exclusion criteria (8 listed)

Untreated and/or uncontrolled bacterial, fungal, or viral infection
Pregnancy, breast-feeding or planning to become pregnant during the study period
For women of childbearing age, lack of effective contraception throughout the duration of participation in the study
Being treated with abatacept or belatacept within 3 months prior to inclusion
Known hypersensitivity to abatacept or belatacept

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Abatacept 250 MGAlso: ORENCIA® BMSAbatacept will be administered by intravenous injection over 1h15 to 2h30 on D1, D5+/-2 and D14+/-2 at 10mg/kg (arm A), or 20mg/kg (arm B) or 25mg/kg (arm C) depending on the randomization (max 3 000 mg per administration). Starting Day 21 (after evaluation of the primary outcome), other injection of abatacept may be given (D22 at D90) with dosage (10 or 20mg/kg max) decided by the treating physician (max 2 500 mg per administration) as a function of the relapse or not of the ICI myocarditis after immunosuppressant therapeutics tapering. After day 21, the administrations will be carried out in open but the blind administration 1 to 3 (D1 to D21) will be kept.	Drug	A-10mg/kg, B-20mg/kg, C-25mg/kg

Primary outcome

Proportion of patients with an adequate circulating monocytes CD86 receptor occupancy (CD86RO) saturation ≥ 80%
Time frame: CD86RO will be assessed versus baseline levels (1 to 3 hours before 1st abatacept administration for baseline) and then, once 1 to 3 hours and 12 to 72 hours after the 1st, 2nd and 3rd abatacept administration, and at Day 21 .
A patient will be considered with an adequate CD86RO saturation (≥80%) within the first weeks of treatment if at least three CD86RO assessment are over 80% until Day 21 after the first abatacept administration.

52 secondary outcomes

Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: one to 3 hours before abatacept treatment (Baseline), once 1 to 3 hours after, and once 12 to 72 hours after the first administration, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 90
Quantification of proxies reflecting the resolution of systemic immune activation
Time frame: Between Day 0 and Day 21
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: Between Day 0 and Day 21, and Day 90
Quantification of proxies reflecting the resolution of myocarditis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the resolution of myocarditis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the resolution of myocarditis
Time frame: At admission, Day 5, Day 14, Day 21, Day 90 and then every 3 months up to one year
Quantification of proxies reflecting the resolution of myocarditis
Time frame: At admission, Day 21, Day 90, 6 months and one year
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis:
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Quantification of proxies reflecting the involvement and resolution of any associated myositis:
Time frame: These modalities will be assessed at least once as soon as possible after admission, 3 months and one year after the first abatacept administration.
Pharmacokinetic/pharmacodynamic (PK-PD) modelling of abatacept in ICI-myocarditis
Time frame: Throughout the study completion (up to one year after randomization)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
Derived from this study: PubMed 39743436Salem JE, Ederhy S, Belin L, Zahr N, Tubach F, Procureur A, Allenbach Y, Rosenzwjag M, Bretagne M. Abatacept dose-finding phase II triaL for immune checkpoint inhibitors myocarditis (ACHLYS) trial design. Arch Cardiovasc Dis. 2025 Feb;118(2):106-115. doi: 10.1016/j.acvd.2024.12.005. Epub 2024 Dec 20.
Individual participant dataSharing planned: Yes. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

Related trials for Myocarditis

Recruiting
Baduanjin Rehabilitation for Functional Restoration in ICI-Associated Myocarditis
Immune Checkpoint Inhibitors Related Myocarditis
Not yet recruitingObservational study
Monitoring and Rehabilitation for ICIACI Rehabilitation：A Cohort Study
Immune Checkpoint Inhibitor-Related Myocarditis
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
Recruiting
Heart@Home Safety and Efficacy of Hospital-at-Home Care Versus Standard Hospitalization in Cardiac Patients
Myocardial Infarction, Myocarditis Acute
RecruitingObservational study
MYocarditis and/or Pericarditis Following mRNA COVID-19 VACCination National Surveillance Study
Myocarditis, Myocarditis Acute

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joe-Elie SALEM, Pr study director

Pitie Salpetriere Hospital , APHP

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Abatacept 250 MG in people with Myocarditis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

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 10 inclusion and 8 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: finished, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with an adequate circulating monocytes CD86 receptor occupancy (CD86RO) saturation ≥ 80% (time frame: CD86RO will be assessed versus baseline levels (1 to 3 hours before 1st abatacept administration for baseline) and then, once 1 to 3 hours and 12 to 72 hours after the 1st, 2nd and 3rd abatacept administration, and at Day 21 .). 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 NCT05195645, 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 16 Jul 2026.