Anakinra in the Treatment of Pediatric Acute Myocarditis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To compare the efficacy of Anakinra vs placebo, on top of the standard of care, on restoration of myocardial function at 3 days following treatment initiation, in children admitted for acute myocarditis in intensive care units.

Secondary objectives 8

1. To describe the proportion of patients treated with Anakinra with a restoration of myocardial function at other timestamps (7 days and 28 days following treatment initiation).
2. To compare the efficacy of Anakinra vs placebo on the delay until recovery of normal left ventricular ejection fraction during the first 3 days following treatment initiation
3. To compare the need for extracorporeal membrane oxygenation (ECMO) in the Anakinra group vs the placebo group at 3 days following treatment initiation
4. To describe the need for heart transplant at 6 months following treatment initiation in patients treated with Anakinra
5. To describe all-cause mortality at 6 months following treatment initiation in patients treated with Anakinra
6. To describe cardiovascular-related mortality at 6 months following treatment initiation in patients treated with Anakinra
7. To assess the safety of Anakinra in the setting of pediatric acute myocarditis
8. a- o NT proBNP at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation o Troponin T at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation o Proportion of children with ventricular tachycardia assessed by EKG at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation b- o NT proBNP at 7 days following treatment initiation o Troponin T at 7 days following treatment initiation

Conditions and MedDRA coding

PEDIATRIC ACUTE MYOCARDITIS

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Children from ≥ 3 months to < 18 years of age
2. Hospitalized in the Intensive Care Unit (ICU) for acute myocarditis defined as : - a reduced left ventricle ejection fraction below 50% and - troponin T rise (>1.5x normal range)
3. Signed informed consent by legal representative and patient according to the legislation.

Exclusion criteria 17

1. Children weighing less than 5 Kgs
2. Pregnancy** or breastfeeding
3. No affiliation to the Social Security
4. Current enrollment in another clinical trial
5. Known anterior cardiomyopathy or operated cardiopathy
6. Neutropenia (< 1,5 × 10^9 /L).
7. Known hypersensitivity to Anakinra or any of its excipients (citric acid anhydrous, sodium chloride, disodium EDTA dihydrate, polysorbate 80, E. coli derived proteins)
8. Administration of a live vaccine in the 4 weeks prior to inclusion
9. Hepatitis B infection, defined as positive HBsAg and/or detectable HBV DNA (PCR). Due to the urgent need to start treatment, inclusion may occur before hepatitis B screening results are available. If hepatitis B infection is subsequently confirmed, the study treatment will be immediately discontinued.
10. Anti TNF-α within the past 14 days
11. Malignancy or history of malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study
12. Ongoing or recent use of any other medication Known inhibitors/inducers of cytochrome P450
13. - Patients with increased risk of Tuberculosis (TB ) infection - Recent tuberculosis infection or with active TB o Close contact with a patient with TB o Patients recently arrived less than 3 months from a country with high prevalence of TB o A chest radiograph suggestive of TB
14. - Patients with overt concomitant bacterial infection
15. - Patients with overt concomitant bacterial infection
16. - Patients with any type of immunodeficiency or cancer
17. - Inability of the legal representative (and the patient, when applicable) to understand the national language (French)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of children with recovered left ventricle ejection fraction (LVEF ≥ 50%) measured by echocardiography at 3 days after treatment initiation. Patients who die within the first 3 days after treatment initiation or patients who still require ECMO at 3 days after treatment initiation will be considered as a failure.

Secondary endpoints 8

1. Proportion of children with recovered left ventricle ejection fraction (LVEF ≥ 50%) measured by echocardiography at 7 and 28 days after treatment initiation. Patients who die or undergo heart transplant within the first 7 and 28 days after treatment initiation respectively will be considered as a failure (i.e, LVEF < 50%). Patients who still require ECMO at 7 and 28 days after treatment initiation respectively will also be considered as failure (i.e., LVEF < 50%).
2. Time to recovery of normal left ventricular ejection fraction (LVEF ≥ 50%) within the first 3 days after treatment initiation 3- Proportion of children requiring ECMO within the first 3 days after treatment initiation
3. Proportion of children requiring ECMO within the first 3 days after treatment initiation
4. Proportion of children who undergo heart transplant within 6 months after treatment initiation
5. Time to all-cause death within 6 months after treatment initiation
6. Time to cardiovascular-related death within 6 months after treatment initiation
7. Proportion of children with drug-related side effects (hypersensitivity, neutropenia, drug-related liver enzymes elevation…)
8. a- o NT proBNP at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation o Troponin T at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation o Proportion of children with ventricular tachycardia assessed by EKG at inclusion and at 24 hours, 48 hours, 72 hours following treatment initiation b- o NT proBNP at 7 days following treatment initiation o Troponin T at 7 days following treatment initiation o Proportion of children with ventricular tachyca

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Ramy CHARBEL

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Ramy CHARBEL

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications