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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Sheba Medical Center
Sponsor:
Information provided by (Responsible Party):
Prof.Avi Livneh, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01705756
First received: September 27, 2012
Last updated: November 3, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Familial Mediterranean Fever,
Drug: Kineret
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-Controlled Study of the Efficacy and Safety of Kineret (Anakinra), in Adult Patients With Colchicine-Resistant Familial Mediterranean Fever

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Number of patients with less than a mean of one FMF attack per month [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Number of serious adverse events [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

    Secondary endpoint is defined as total number of serious adverse events per 4 months in each study group. SAE is defined as an adverse event that meets one or more of the following criteria/outcomes:

    • Death
    • Life-threatening (i.e., at immediate risk of death)
    • In-patient hospitalization or prolongation of existing hospitalization
    • Persistent or significant disability/incapacity
    • Congenital anomaly/birth defect


Estimated Enrollment: 50
Study Start Date: November 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Vehicle
•Patients randomized to placebo will receive syringes identical to active drug (100 mg prefilled syringes for subcutaneous injection) filled with drug vehicle
Experimental: Kineret (Anakinra)
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
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.
Other Name: Anakinra

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A subject must fulfil the following criteria in order to be included in the study:

  1. 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).
  2. 18-65 years of age
  3. Verified as mutations in both alleles of the MEFV gene, thus including homozygous and compound heterozygous patients
  4. Patient compliant with maximum tolerable dose of colchicine (up to 3 mg/day)
  5. At least one FMF attack per month in chest, abdomen or joints (definition of attack see above)
  6. Adequate contraception for sexually active male and female patients

Exclusion Criteria:

The presence of any of the following will exclude a subject from inclusion in the study:

  1. Patient pregnant at enrolment visit
  2. Prior or existing malignancy
  3. Active infection
  4. 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
  5. Live vaccinations last three months before enrolment
  6. Sociopsychological state threatening compliance with the treatment protocol
  7. Alcohol or substance abuse
  8. Concomitant medication with biological or anti-rheumatic disease-modifying drugs or systemic steroids
  9. Any prior use of IL-1 inhibitory drugs
  10. Associated disease that could interfere with clinical assessment:

    1. Rheumatic disorder
    2. Systemic disease, e.g. autoimmune or other autoinflammatory disorder, diabetes, hypertension, vasculitis, Behçet's disease
    3. Gastrointestinal disorder, e.g. Crohn's disease, ulcerative colitis, irritable bowel syndrome
    4. Cardiovascular disorder, e.g. post myocardial infarction, angina
    5. Pulmonary disorder, e.g. COPD, pulmonary hypertension
    6. Any other condition which in the opinion of the investigator makes the subject unsuitable for inclusion
  11. Enrolment in another concurrent clinical study, or intake of an investigational drug, within three months prior to inclusion in this study
  12. Failure or refusal to cooperate with given instructions

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01705756

Locations
Israel
Sheba Medical Center Recruiting
Tel- Hashomer, Ramat- Gan, Israel, 52621
Contact: Avi Livneh, prof.    +972-3-5302156    Avi.Livneh@sheba.health.gov.il   
Contact: Carni Gaoni, Vice President    +972-9-7604596    Cgaoni@megapharm.co.il   
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Avi Livneh, professor Sheba Medical Center, Tel- Hashomer, Ramat- Gan, Israel.
  More Information

No publications provided

Responsible Party: Prof.Avi Livneh, Principal Investigator, Head of Internal Medicine "F" , Director of national center of FMF, Israel, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01705756     History of Changes
Other Study ID Numbers: SHEBA-11-8557-AL-CTIL
Study First Received: September 27, 2012
Last Updated: November 3, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Sheba Medical Center:
Colchicine
Anakinra
FMF
Colchicine resistance

Additional relevant MeSH terms:
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Brucellosis
Fever
Gram-Negative Bacterial Infections
Bacterial Infections
Body Temperature Changes
Signs and Symptoms
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Colchicine
Interleukin 1 Receptor Antagonist Protein
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014