A Randomized Placebo-Controlled Study of the Efficacy and Safety of Kineret (Anakinra), in Adult Patients With Colchicine-Resistant Familial Mediterranean Fever
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number of patients with less than a mean of one FMF attack per month
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •18-65 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
排除标准
- •The presence of any of the following will exclude a subject from inclusion in the study:
- •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
- •Any other condition which in the opinion of the investigator makes the subject unsuitable for inclusion
- •Enrolment in another concurrent clinical study, or intake of an investigational drug, within three months prior to inclusion in this study
- •Failure or refusal to cooperate with given instructions
研究组 & 干预措施
Vehicle
•Patients randomized to placebo will receive syringes identical to active drug (100 mg prefilled syringes for subcutaneous injection) filled with drug vehicle
干预措施: Kineret (Drug)
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.
干预措施: Kineret (Drug)
结局指标
主要结局
Number of patients with less than a mean of one FMF attack per month
时间窗: 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
次要结局
- Number of serious adverse events(4 months)
研究者
Prof.Avi Livneh
Principal Investigator, Head of Internal Medicine "F" , Director of national center of FMF, Israel
Sheba Medical Center