Therapeutic approach in Colchicine-resistant Recurrent pEricarditis in children: an open-label randomized trial comparing Anakinra vs sTEroids

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Giannina Gaslini Institute For Scientific Hospitalization And Care

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

22 Mar 2024 → ongoing

Decision date (initial)

2023-10-23

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Italian Ministry of Health

External identifiers

EU CT number

2023-504756-96-00

WHO UTN

U1111-1290-2511

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Main objective of this study is to demonstrate that anakinra is more effective than steroids to control the disease and prevent further flares in paediatric (from 8 months to < 18 years) patients with RP not responding to first line treatment with NSAIDS and colchicine at the proper dosage, or in case of colchicine intolerance.

Secondary objectives 1

1. In the study we aim to collect the RNA to perform trascriptomic study in the patients enrolled in the study at different timepoints (at baseline, at day 14, 28 and, in responder patient, at the time of the relapse or at last visit of the study). Through a correlation between the clinical, laboratory parameters and the response to treatment with the trascriptome analysis, we aim to identify transcripts associated to a higher probability of response to treatment and long-term remission off-therapy.

Conditions and MedDRA coding

Recurrent pericarditis, idiopathic or secondary to invasive cardiac procedures, not responsive to colchicine and NSAIDs after the first relapse.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male and female patients, from 8 months to less than 18 years
2. Parent or legal guardian written informed consent and child assent, if appropriate, are required before any assessment is performed
3. Diagnosis of relapse of pericarditis in a patient with previous diagnosis of acute pericarditis (idiopathic or secondary to invasive cardiac procedures)
4. Inadequate response or intolerance to non-steroidal anti-inflammatory drugs or colchicine

Exclusion criteria 14

1. Pericarditis secondary to a known infection (viral, bacterial, mycobacterial)
2. Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening
3. Use of steroids at the dosage of 1 mg/kg/day of prednisone or equivalent for at least 5 days in the 30 days before randomization
4. Live vaccinations within 1 months prior to the start of the trial and during the trial
5. Pregnancy, confirmed by a positive hCG laboratory test
6. Female adolescents (<18 years of age) of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of contraception
7. Pericarditis in a patient with a previous diagnosis of any neoplasm and without complete recovery from at least one year
8. Patients fulfilling diagnostic criteria for an autoimmune systemic disease
9. Patients with a previous diagnosis of a genetically confirmed autoinflammatory disease
10. Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for immunomodulatory therapy
11. Main alteration in the blood count: Neutropenia (absolute neutrophil count <1000/mmc), Thrombocytopenia (platelets <100.000/mmc) or Severe anaemia (Hb < 7.5 mg/dl)
12. Presence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B or Hepatitis C infections
13. Evidence of active or latent tuberculosis (TB) determined by positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (>5 mm induration) within 2 months prior to randomization
14. Presence of laboratory or echocardiographic findings of myopericarditis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Complete response of disease flare at day 7
2. Lack of relapse at month 3

Secondary endpoints 8

1. Time to achieve a complete control of the flare
2. Time to flare after treatment tapering
3. Number of flares at follow up
4. Behavior of acute phase reactants during 6 months of observation
5. Quality of life
6. Safety (registration of side effects occurred during the whole period of the study)
7. Number of day of hospitalization
8. Transcriptomic study

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Giannina Gaslini Institute For Scientific Hospitalization And Care

Sponsor organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Address

Via Gerolamo Gaslini 5

City

Genoa

Postcode

16147

Country

Italy

Scientific contact point

Organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Contact name

Roberta Caorsi

Public contact point

Organisation

Giannina Gaslini Institute For Scientific Hospitalization And Care

Contact name

Nicolino Ruperto

Locations

1 EU/EEA country · 15 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 5 files

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

Application history

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