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

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ClinicalTrials.gov Identifier: NCT01705756
Recruitment Status : Completed
First Posted : October 12, 2012
Last Update Posted : July 21, 2017
Sponsor:
Information provided by (Responsible Party):
Prof.Avi Livneh, Sheba Medical Center

Study Description
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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.


Condition or disease Intervention/treatment Phase
Familial Mediterranean Fever Drug: Kineret Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : November 2012
Actual Primary Completion Date : December 2014
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Family Issues Fever

Arms and Interventions
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Arm Intervention/treatment
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
 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
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


Outcome Measures
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Primary Outcome Measures :
  1. Number of patients with less than a mean of one FMF attack per month [ Time Frame: 4 months ]
    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 :
  1. Number of serious adverse events [ Time Frame: 4 months ]

    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01705756


Locations
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Israel
Sheba Medical Center
Tel- Hashomer, Ramat- Gan, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
Investigators
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Principal Investigator: Avi Livneh, professor Sheba Medical Center, Tel- Hashomer, Ramat- Gan, Israel.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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    
Other Study ID Numbers: SHEBA-11-8557-AL-CTIL
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: July 21, 2017
Last Verified: July 2017
Keywords provided by Prof.Avi Livneh, Sheba Medical Center:
Colchicine
Anakinra
Colchicine resistance
Familial Mediterranean fever
Additional relevant MeSH terms:
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Brucellosis
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Fever
Body Temperature Changes
Gram-Negative Bacterial Infections
Bacterial Infections
 Bacterial Infections and Mycoses
Infections
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents