Myocarditis Therapy with IL-1 inhibitor (MYTH-1): a double-blind, phase IIa, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of anakinra in addition to standard of care for the treatment of virus-negative myocarditis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 Sep 2021 → 18 Feb 2026

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515472-13-00

EudraCT number

2018-003472-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the benefit of Anakinra combined with standard immunosuppressive therapy with azathioprine and prednisone in the treatment of virus-negative myocarditis.

Conditions and MedDRA coding

endomyocardial biopsy (EBM)-proven virus-negative myocarditis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 18 Years to 75 Years
2. Myocarditis defined by cardiac magnetic resonance (according with Lake Louise Criteria) and virus-negativity defined by on endomyocardial biopsy.
3. Any impairment of left ventricular ejection fraction (LV-EF) <55% on Trans Thoracic Echocardiography.
4. Ability to sign an informed consent.

Exclusion criteria 17

1. Coronary artery stenosis > 50% at angiography or coronary CT Scan (acceptable if performed during the last 12 months).
2. Evidence of genome of cardiotropic viruses by Polymerase chain reaction on EBM.
3. Clinical suspicion or proven underlying disease: Lyme disease, any other bacterial disease possibly responsible for myocarditis, trypanosomiase disease, giant cell myocarditis.
4. Known presence or suspicion of active or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
5. Pregnancy, breastfeeding. Female patients of childbearing potential may participate if adequate contraception is used during the study. (For the purposes of this trial, women of childbearing potential are defined as “All female subjects after puberty unless they are post-menopausal for at least 2 years or are surgically sterile.”
6. Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients or to Escherichia coli-derived proteins).
7. Presence of neutropenia < 1,5.109/L).
8. Renal failure as defined by estimated glomerular filtration rate (eGFR) <30 ml/min, according to Cockcroft-Gault.
9. Any comorbidity limiting survival or conditions predicting inability to complete the study.
10. History of malignancy in the previous 5 years. Exceptions are basal cell skin cancer, carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy.
11. Any other previous biological treatment administered within 5 -half lives of the specific drug.
12. Any concomitant immune-suppressive medications other than those included in the study protocol.
13. Therapy with prednisone >10 mg daily and/or immuno-suppressive agents within 3 months before the enrolment.
14. Hepatic impairment = Child-Pugh Class C
15. Mechanical ventilation circulatory assistance.
16. Congenital and/or acquired valvular disease or any other heart disease that could justify the severity of cardiac dysfunction.
17. Major surgery within 2 weeks prior to randomization, or unhealed operation wounds.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the benefit of Anakinra combined with standard immunosuppressive therapy in improving Left Ventricular Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) at 2 months.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Giacomo De Luca

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Giacomo De Luca

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 4 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