Kineret (Anakinra), in Adult Patients With Colchicine-Resistant Familial Mediterranean Fever

NCT01705756 | Completed Phase 3

• 1 other identifier: SHEBA-11-8557-AL-CTIL
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

FMF is the most common periodic fever with a worldwide patient population estimated as 150,000, mainly located in the Eastern Mediterranean basin. colchicine is the established therapy of choice ,however, around 20.000 patients worldwide fail to respond or cannot tolerate therapeutic doses, thereby suffering from recurrent debilitating, severe, painful attacks of peritonitis, pleuritis and synovitis and are at risk to die from reactive amyloidosis .Mutation-induced reduction in pyrin/ marenostrin activity is thought to underlie the disease by leading to NALP3 inflammasome activation ,and thereby to IL-1β related burst of inflammation. The IL-1 receptor antagonist Kineret (Anakinra), seems to be the most appropriate response to the uncontrolled IL-1β elevation. Indeed, an increasing number of reports over the last few years indicate a good response to Kineret (Anakinra), in colchicine-resistant FMF ,also in children ,however, no controlled study has thoroughly evaluated the efficacy and safety of this treatment. Study outline: The study aims to run at the FMF centre in Sheba Medical Center, covering more than 10,000 patients. The study will evaluate the effect of recombinant IL-1 receptor antagonist, Kineret (Anakinra), on the frequency of FMF attacks in patients that, despite maximum tolerable dose of colchicine, present with more than one attack per month. The study is designed as a randomised, placebo-controlled, double-blind study. 50 patients will be randomised to treatment with either Kineret (Anakinra), or placebo treatment for 4 months.

Conditions

Familial Mediterranean Fever

Keywords

Colchicine; Anakinra; Colchicine resistance; Familial Mediterranean fever

Outcome Measures

Primary Outcomes (1)

• Number of patients with less than a mean of one FMF attack per month

  Total number of FMF attacks in abdominal, thoracic, skin or joint locations during the observational period (4 months) as recorded in the patient diary, devided by 4 for each patient will result in number of attacks per one month. The number of patients with less than 1 attack per month will be compared between the 2 study groups

  4 months

Secondary Outcomes (1)

• Number of serious adverse events

  4 months

Study Arms (2)

Vehicle

PLACEBO COMPARATOR

•Patients randomized to placebo will receive syringes identical to active drug (100 mg prefilled syringes for subcutaneous injection) filled with drug vehicle

Drug: Kineret

Kineret (Anakinra)

EXPERIMENTAL

Patients randomized to active drug will receive Kineret (Anakinra), 100 mg prefilled syringes for subcutaneous injection, once a day for 4 months. The syringes will arrive relabeled from the supplier (SOBI) to Sheba Medical Center. They will be stored at the PI's store room in a temperature controlled refrigerator.

Drug: Kineret

Interventions

Kineret DRUG

Patients randomized to active drug will receive Kineret(Anakinra), 100 mg prefilled syringes for subcutaneous injection, once a day for 4 months. The syringes will arrive relabeled from the supplier (SOBI) to Sheba Medical Center. They will be stored at the PI's store room in a temperature controlled refrigerator.

Also known as: Anakinra

Kineret (Anakinra); Vehicle

Eligibility Criteria

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

You may qualify if:

• A subject must fulfil the following criteria in order to be included in the study:
• FMF diagnosed as per the Tel-Hashomer criteria -(Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum.1998 Aug; 41(8):1516-7-Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M).
• years of age
• Verified as mutations in both alleles of the MEFV gene, thus including homozygous and compound heterozygous patients
• Patient compliant with maximum tolerable dose of colchicine (up to 3 mg/day)
• At least one FMF attack per month in chest, abdomen or joints (definition of attack see above)
• Adequate contraception for sexually active male and female patients

You may not qualify if:

• Patient pregnant at enrolment visit
• Prior or existing malignancy
• Active infection
• Manifest renal failure with Creatinine clearance \<30mL/min as determined by the equation Creatinine clearance (ml/min) = (140-age) x Wight (Kg) /72 x serum creatinine (mg/dcl) For women one should multiply the results by 0.8
• Live vaccinations last three months before enrolment
• Sociopsychological state threatening compliance with the treatment protocol
• Alcohol or substance abuse
• Concomitant medication with biological or anti-rheumatic disease-modifying drugs or systemic steroids
• Any prior use of IL-1 inhibitory drugs
• Associated disease that could interfere with clinical assessment:
• Rheumatic disorder
• Systemic disease, e.g. autoimmune or other autoinflammatory disorder, diabetes, hypertension, vasculitis, Behçet's disease
• Gastrointestinal disorder, e.g. Crohn's disease, ulcerative colitis, irritable bowel syndrome
• Cardiovascular disorder, e.g. post myocardial infarction, angina
• Pulmonary disorder, e.g. COPD, pulmonary hypertension

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Related Publications (1)

• Ben-Zvi I, Kukuy O, Giat E, Pras E, Feld O, Kivity S, Perski O, Bornstein G, Grossman C, Harari G, Lidar M, Livneh A. Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2017 Apr;69(4):854-862. doi: 10.1002/art.39995.

  PMID: 27860460 DERIVED

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

• Avi Livneh, professor

  Sheba Medical Center, Tel- Hashomer, Ramat- Gan, Israel.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Internal Medicine "F" , Director of national center of FMF, Israel

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: October 12, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2015
• Last Updated: April 2, 2024

Record last verified: 2024-03

Locations

IL (1)