Targeted therapy with anakinra for dilated cardiomyopathy: phase IIa randomized double blind monocentric clinical trial to evaluate the efficacy and safety of anakinra plus standard of care vs standard of care alone in the treatment of dilated cardiomyopathy.

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] - Immune System Diseases [C20]

Trial duration

25 May 2023 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514861-21-00

EudraCT number

2020-005507-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy of IL-1 therapeutic blockade with Anakinra in improving Left Ventricular Ejection Fraction (LVEF) assessed by Trans Thoracic Echocardiograhy (TTE) at 4 weeks.

Conditions and MedDRA coding

Inflammatory dilated cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age: 18 Years to 75 years;
2. Diagnosis of DCM according to current guidelines;
3. Symptoms of HF not improved or worsened despite at least 3 months of optimal therapy;
4. LVEF<50% at echocardiography (TTE), not improved or worsened despite at least 3 months of optimal therapy;
5. Increased high-sensitive troponin T (hs-TnT), and/or findings suggestive for actual or prior myocardial inflammation at cardiac MRI (within 6 months);
6. Absence of coronary artery disease (coronary artery stenosis > 50% at angiography or coronary CT Scan, acceptable if performed during the last 12 months).
7. Ability to sign an informed consent;
8. Presence of CD3+ >7/mm2 cells on EMB, in addiction to all the aformentioned inclusion criteria, will be needed exclusively to be enrollend in the Phase IIa Randomized Double Blind monocentric Clinical Trial.

Exclusion criteria 18

1. Genetic DCM;
2. Toxin abuse/exposure (Alcohol, amphetamines, cocaine, anthracyclines [e.g., doxycycline], trastuzumab, clozapine, chloroquine, carbon monoxide, cobalt, lead, mercury;
3. Clinical suspicion or proven underlying active, chronic or recurrent bacterial, fungal or viral infections, including tuberculosis, or HIV infection or epatitis B virus (HBV) or hepatitis C virus (HCV) infection, Lyme disease, Chagas disease or any other bacterial/fungeal/protozoal disease possibly responsible for DCM;
4. Endocrine, infiltrative (Cushing’s disease, acromegaly not clinically controlled hypo/hyperthyroidism, pheochromocytoma) or neuromuscular diseases (Dystrophinopathies [Duchenne/Becker muscular dystrophy/X-linked DCM], Limb-girdle muscular dystrophies, Facioscapulohumeral muscular dystrophy, Emery-Dreifuss muscular dystrophy, Friedreich’s ataxia, Myotonic dystrophy);
5. Contraindications to EMB;
6. Contraindications to PET/MRI (i.e. gadolinium hypersensitivity, renal failure, claustrophobia, pacemaker or ICD device, blood glucose>12.5 mmol/L);
7. 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;
8. Any other concomitant or previous biological anti-cytokine treatment administered within 5 -half lives of the specific drug;
9. Renal failure as defined by estimated glomerular filtration rate (eGFR) <30 ml/min, according to Cockcroft-Gault;
10. Hepatic impairment = Child-Pugh Class C;
11. Mechanical ventilation circulatory assistance;
12. 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.”)
13. Contra-indication to ANAKINRA (known hypersensitivity to the active substance or to any of the excipients or to Escherichia coli-derived proteins).
14. Presence of neutropenia < 1,5.109/L), or thrombocytopenia < 50.000/mm3;
15. Any comorbidity limiting survival or conditions predicting inability to complete the study;
16. Any concomitant immune-suppressive medications (i.e. azathioprine, methotrexate, cyclosporine, mycophenolate, cyclophosphamide, rituximab, tacrolimus);
17. Therapy with prednisone >10 mg daily and/or any immuno-suppressive agents within 3 months before the enrolment;
18. Congenital and/or acquired valvular disease or any other heart disease that could justify the severity of cardiac dysfunction; Major surgery within 2 weeks prior to randomization, or unhealed operation wounds.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement in left-ventricular function, based on the increase of left ventricular (LV) ejection fraction (EF) assessed by transthoracic echocardiography at 4-weeks.

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 6 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