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

NCT ID: NCT06336733

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-04
• Study Completion Date: 2026-12-04

Brief Summary

To evaluate the efficacy on clinical symptoms in case of FMF attack among FMF patients resistant to Colchicine of

• on demand anakinra treatment (100 mg/d from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) associated with daily colchicine.
• compared to analgesic associated with daily colchicine in patients refusing continuous anti-IL-1 treatment.

Detailed Description

KIN-ATTACK-FMF will be the first randomized prospective study comparing the efficacy of on-demand anakinra versus standard of care treatment in patients with colchicine resistant symptoms of FMF who refuse continuous daily therapy.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (100,000 people worldwide and 7500 in France). It causes monthly recurrent febrile abdominal pain with a biological inflammatory syndrome.

To prevent FMF attacks and development of inflammatory amyloidosis (IA) daily oral colchicine is the first line recommended treatment. 10 to 15% of patients are resistant to colchicine: persistence of 1attack/month over a period of 3 months (in spite of taking the maximum tolerated dose of colchicine daily). Subcutaneous anti-interleukin 1 biotherapies were recently allowed in France combined to daily oral colchicine for colchicine resistant FMF: anakinra (short-acting anti-IL1 drug, daily) or canakinumab (long acting monoclonal anti IL1 antibody, every 2 months). These treatments cost respectively 30 and 12,000 euros/injection.

If abdominal attacks are controlled by colchicine, patients still suffer from lower limb pains, particularly erysipelas like erythema and exertional myalgias, which are very disabling and require use of analgesics or anti-inflammatory. However, in the referral center, 20% of colchicine resistant FMF patients don't receive chronic anti IL1 treatment, despite an indication. Main reasons are: 1-they do not want to inject themselves every day (for anakinra); 2-women of childbearing age are afraid about the impact of biotherapies on their fetus; 3-some do not want to ask for 100% coverage because of the biotherapy cost; 4- the authorization for anti IL1 in FMF is very recent and they want more certainty about its effectiveness.

The hypothesis of the study is that on-demand use of Anakinra from onset of attack until 24 hours of remission (during 7 days maximum) associated with chronic daily colchicine as background treatment in case of attack could stop it, thus reducing its length and pain compared to standard of care treatment which includes only classical antalgics with colchicine in patients refusing chronic daily anti IL1 treatment.

In the experimental arm, patients receive on demand anakinra treatment (100 mg/d from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) associated with daily colchicine. In the control arm, patients receive analgesics associated with daily colchicine.

50 participants should be included in the study during a period of 24 months with a 6 months participation period (treatment + follow up)

It's a Multicenter national study including 11 centers.

Conditions

FMF

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ANAKINRA on Demand

On demand Anakinra 100 mg/j from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) + colchicine + on demand analgesics

Group Type: EXPERIMENTAL

ANAKINRA

Intervention Type: DRUG

On demand Anakinra 100 mg/j from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) + colchicine + on demand analgesics

Standard of Care

Usual analgesics + colchicine

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

ANAKINRA

On demand Anakinra 100 mg/j from the prodromal phase of the attack until 24 hours of remission (during 7 days maximum) + colchicine + on demand analgesics

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >= 6 years old with no upper limit
• Proven FMF according to Livneh international criteria 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-months 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)
• Patient who do not have biological inflammation between attacks
• Written informed consent of the patients and or his legal representatives

Exclusion Criteria

• 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 10^9/l)
• Inability to provide informed consent
• Ongoing chronic treatment with anti IL1 biotherapy since at least 3 months
• Pregnant women
• Women in labor and nursing mothers
• Patients in emergency situations and people hospitalized without consent
• No health care insurance
• Contraindication to colchicine
• Patient participating in another interventional clinical trial
• Patient deprived of liberty
• Patient under guardianship or curatorship
• Patient under court protection

Randomization criteria :

• Absence of active or latent tuberculosis (no tuberculosis sign on chest X-ray and a negative quantiferon)
• Negative pregnancy test

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Léa Léa Léa SAVEY

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Service de Médecine interne Hopital Tenon

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Léa SAVEY

Role: CONTACT

lea.savey@aphp.fr

0033 1 56 01 67 91

Sophie Georgin-Lavialle, MD,PHD

Role: CONTACT

sophie.georgin-lavialle@aphp.fr

00 33 1 56 01 74 31

Facility Contacts

Léa SAVEY

Role: primary

lea.savey@aphp.fr

00 33 1 56 01 60 77

Sophie Georgin-Lavialle, MD,PHD

Role: backup

sophie.georgin-lavialle@aphp.fr

0 33 1 56 01 74 31

Other Identifiers

APHP220828

Identifier Type: -

Identifier Source: org_study_id