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

NCT06336733 | Recruiting Phase 3 DMC

• 1 other identifier: APHP220828
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

FMF

Keywords

Anakinra; Familial Mediterranean fever; Colchicine resistance; Randomized prospective study

Outcome Measures

Primary Outcomes (1)

• Mean number of FMF-attacks per month at 6 months of treatment.

  * FMF attacks is defined by a painful (consensual definition) manifestation during 12 to 72 hours, in either : * abdomen (with features consistent with a diagnosis of peritonitis), * chest (with features consistent with a diagnosis of pleuritis), * joints (with features consistent with a diagnosis of lower extremity large joint monoarthritis), * skin (with features consistent with a diagnosis of erysipeloid rash) * The painful manifestation can be (or not) accompanied by fever of ≥ 38°C Patients will be asked to note the number of days of pain of each inflammatory attack on a diary.

  At Months 0 (baseline), Month 1, Month 3 and Month 6

Secondary Outcomes (6)

• Cumulative days of FMF attack treatment from randomization to 6 months

  At Months 0 (baseline), Month 1, Month 3 and Month 6

• AIDAI (Auto-inflammatory Diseases activity index) score

  At Months 0 (baseline), Month 1, Month 3 and Month 6

• Number of painful days and severity of FMF attacks occurring between randomization and M6

  At Months 0 (baseline), Month 1, Month 3 and Month 6

• Quality of life score measured by EuroQOL questionnaire (EQ-5D5L)

  At Months 0 (baseline), Month 1, Month 3 and Month 6

• Number of local cutaneous reactions at 6 months (erythema and oedema involving the injection sites) in the anakinra arm

  At Months 0 (baseline), Month 1, Month 3 and Month 6

Study Arms (2)

ANAKINRA on Demand

EXPERIMENTAL

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

Drug: ANAKINRA

Standard of Care

NO INTERVENTION

Usual analgesics + colchicine

Interventions

ANAKINRA 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

ANAKINRA on Demand

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Evidence of active tuberculosis
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Médecine interne Hopital Tenon

Paris, 75020, France

RECRUITING

MeSH Terms

Conditions

Familial Mediterranean Fever

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Léa Léa Léa SAVEY

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Léa SAVEY

CONTACT

0033 1 56 01 67 91; lea.savey@aphp.fr

Sophie Georgin-Lavialle, MD,PHD

CONTACT

00 33 1 56 01 74 31; sophie.georgin-lavialle@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 29, 2024
• Study Start: June 4, 2024
• Primary Completion (Estimated): December 4, 2026
• Study Completion (Estimated): December 4, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)