Randomized controlled trial in patients on long-term colchicine with colchicine-resistant familial Mediterranean fever (FMF) to evaluate the efficacy of on-demand Anakinra treatment for painful attacks in patients who refuse continuous daily therapy (KIN-ATTACK-FMF).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

4 Jun 2024 → ongoing

Decision date (initial)

2024-02-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC 2021 (Ministère de la Santé )

External identifiers

EU CT number

2023-506721-11-00

ClinicalTrials.gov

NCT06336733

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

to evaluate the efficacy on clinical symptoms in case of FMF attack among FMF patients resistant to Colchicine who refuse continuous daily therapy of on demand anakinra treatment associated with daily colchicine and on demand antalgics compared to standard of care treatment with on demand antalgics associated with daily colchicine. On demand anakinra defined by: injection of 100 mg/d from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) or 100 mg/d to prevent an attack in the event of a known trigger factor.

Secondary objectives 2

1. Efficacy: – Treatment consumption (anakinra vs analgesics), Alteration of general condition, fever (T°>38°C), arthralgia, skin manifestations, Number and severity of FMFattacks during 6 months, Quality of life at6 months
2. The number of local cutaneous reaction at 6 months , Adverse events

Conditions and MedDRA coding

Familial Mediterranean Fever (FMF)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Age > 6 years old with no upper limit. Proven FMF according to Livneh international criteria (2) and 2 non ambiguous MEFV mutations. Colchicine resistance defined as persistent FMF attack despite the maximum daily posology of colchicine (average one or more attacks per month over a 3-month period). FMF Attack is defined by: - Arthritis or - Chest pain or - Abdominal pain or - Myalgia or - Erysipelas-like skin lesion - Duration of episodes 1–4 days. - Patient refusing daily anakinra injections - Patients covered at 100% by the health insurance (ALD) -Patients who do not have biological inflammation between attacks - Written informed consent of the patients and or his legal representatives

Exclusion criteria 1

1. - Evidence of active tuberculosis - Infection requiring treatment with intravenous antibiotics within 2 weeks prior to Inclusion - History of recurrent infection (Need more than 4 courses of antibiotic treatment per year (in children) or more >2 times per year (in adults), experience pneumonia twice over any time or > 3 bacterial sinusitis in 1 year) - Contraindication to anakinra : -Hypersensitivity to the active substance or to any of the excipients (Citric acid, anhydrous Sodium chloride, Disodium edetate dehydrate, Polysorbate 80, Sodium hydroxide, Water for injections ) or to E. coli derived proteins - Patients with neutropenia (ANC <1.5 x 109/l) - Contraindication to colchicine - Inability to provide informed consent - Ongoing chronic treatment with anti IL1 biotherapy since at least 3 months - Pregnant women or breast feeding - No health care insurance - Patient participating in another interventional clinical trial - Patient deprived of liberty - Patient under guardianship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean number of painful days per month at 6 months of treatment.

Secondary endpoints 2

1. Efficacy: −Cumulative days of FMF attack treatment from randomization to 6 months, - AIDAI (Auto-inflammatory Diseases activity index) score D0 and M6 Number of painful days and severity of FMF attacks (measured by VAS Visual Analogue Scale) occurring between randomization and M6 − Quality of life score measured by EuroQOL questionnaire (EQ-5D5L) at M6
2. Safety: − Number of local cutaneous reaction at 6 months (erythema and oedema involving the injection sites) in the anakinra arm − Proportion of adverse events

Investigational products

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

Test 1

Auxiliary 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

Lea SAVEY

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Fatiha Djennaoui

Locations

1 EU/EEA country · 11 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 15 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