FMFPhase 3KIN-ATTACK-FMFNCT06336733
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
A Phase 3 study testing ANAKINRA in people with FMF, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- FMF
- What is being tested?
- ANAKINRA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 4 Jun 2024to 4 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Service de Médecine interne Hopital Tenon
Paris, 75020
Léa SAVEY, 00 33 1 56 01 60 77, lea.savey@aphp.fr
Sophie Georgin-Lavialle, MD,PHD, 0 33 1 56 01 74 31, sophie.georgin-lavialle@aphp.fr
About this study
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.
Read the 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
- Being tested
- ANAKINRA
- Keywords
- Anakinra, Familial Mediterranean fever, Colchicine resistance, Randomized prospective study
- Medical subject headings
- Familial Mediterranean Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANAKINRADrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: ANAKINRA |
| Standard of Care | No intervention | Usual analgesics + colchicine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The number of days of injections (for anakinra arm) or number of days of consumption of analgesics (for control group) will be collected via a notebook . Safety
Measured: At Months 0 (baseline), Month 1, Month 3 and Month 6
AIDAI (Auto-inflammatory Diseases activity index) score
Patients will complete the AIDAI (Auto-inflammatory Diseases activity index) score monthly.
Measured: 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
Number of painful days will be measured by VAS (Visual Analogue Scale) and collected via a notebook).
Measured: At Months 0 (baseline), Month 1, Month 3 and Month 6
Quality of life score measured by EuroQOL questionnaire (EQ-5D5L)
The EQ5D5L will be completed at each visit
Measured: 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
Number of local cutaneous reaction will be collected via a notebook
Measured: At Months 0 (baseline), Month 1, Month 3 and Month 6
Proportion of Adverse events
Adverse events will be collected via a notebook
Measured: At Months 0 (baseline), Month 1, Month 3 and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2024
- Study start4 Jun 2024
- Primary completion4 Dec 2026 (estimated)
- Study completion4 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FMFStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Léa Léa Léa SAVEY, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06336733
- Sponsor's protocol ID
- APHP220828
- Acronym
- KIN-ATTACK-FMF
- Status last verified
- Jun 2025
- First submitted
- 15 Mar 2024
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables,figures, and appendices) could be shared. Data would be available Beginning 9 months and ending 36 months following article publication with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06336733
- Acronym / sponsor ID
- KIN-ATTACK-FMF / APHP220828
- Conditions
- FMF
- Keywords
- Anakinra, Familial Mediterranean fever, Colchicine resistance, Randomized prospective study
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 4 Jun 2024 (actual)
- Primary completion
- 4 Dec 2026 (estimated)
- Study completion
- 4 Dec 2026 (estimated)
- First posted
- 29 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ANAKINRA on Demand | Experimental | Drug: ANAKINRAOn 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 | No intervention | –Usual analgesics + colchicine |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
- Arthritis or
- Chest pain or
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ANAKINRAOn 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 on Demand |
Primary outcome
Mean number of FMF-attacks per month at 6 months of treatment.
Time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6
* 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.
6 secondary outcomes
Cumulative days of FMF attack treatment from randomization to 6 months
Time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6
AIDAI (Auto-inflammatory Diseases activity index) score
Time frame: 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
Time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6
Quality of life score measured by EuroQOL questionnaire (EQ-5D5L)
Time frame: 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
Time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6
Proportion of Adverse events
Time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables,figures, and appendices) could be shared. Data would be available Beginning 9 months and ending 36 months following article publication with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Léa Léa Léa SAVEY principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ANAKINRA in people with FMF, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Léa SAVEY (0033 1 56 01 67 91, lea.savey@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean number of FMF-attacks per month at 6 months of treatment. (time frame: At Months 0 (baseline), Month 1, Month 3 and Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.