Phase II, IL-1 Trap for Treatment of Familial Mediterranean Fever

用于治疗家族性地中海热的 II 期 IL-1 陷阱

• 批准号: 7782822
• 负责人: STEVEN J SPALDING
• 金额: $ 34.95万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-29 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7782822
• 关键词: Phase; II; IL; Trap; Treatment

DESCRIPTION (provided by applicant): Familial Mediterranean fever is an autosomal recessive autoinflammatory genetic disorder resulting in recurrent episodes of fever, serositis, arthritis and rash. Late complications of untreated FMF include the development of renal amyloidosis. FMF is a rare orphan disease in the United States. Treatment with colchicine is effective in reducing the frequency of episodes in most patients and the development of amyloidosis in nearly all patients. However, there are still 5-15% of patients who continue to have acute FMF episodes despite colchicine therapy or are intolerant of colchicine, usually from gastrointestinal adverse effects. Currently there are no effective alternatives to colchicine. Pyrin, the mutated protein in FMF has an important role in the regulation of Interleukin-1 (lL-1) production and activity. Mutations in pyrin result in increased IL-1 beta levels in mice and humans. Interleukin-1 is an important pro-inflammatory cytokine. Thus, the investigators hypothesize that inhibition of IL-1 will decrease acute episodes in patients with FMF. They propose to use IL-1 Trap, a fusion protein consisting of human IL-1 cytokine receptor extracellular domains and the FC portion of human immunoglobulin G (lgG) that binds and neutralizes IL-1. The investigators will enroll 17 subjects from the age of 4 years, including adults, from multiple centers in the United States with active FMF (at least one episode per month) despite receiving at least 1.2-5.5 mg/d of colchicine (dose dependent on age) or are intolerant of colchicine. Subjects will be diagnosed by clinical criteria with at least one heterozygote mutation of the MEFV (pyrin) gene. Subjects will use a single-subject alternating treatments design with subjects receiving in random order two 3 month courses of IL-1 Trap at 2.2 mg/kg (maximum 160 mg) by weekly subcutaneous (SC) injection and two 3 month courses of comparable volume placebo. Subjects with 2 acute FMF episodes during a treatment course will be able to crossover to the other treatment arm until the end of that treatment course. Results will be analyzed by traditional frequency statistics and by Bayesian hierarchical modeling. The investigators primary aim is to assess the efficacy of IL-1 Trap in decreasing the number of acute FMF episodes while monitoring drug safety. Secondary exploratory aims include determining the proportion of subjects who have no acute FMF episodes while taking IL-1 Trap, determining the proportion of subjects who attain at least a 50% decrease in acute FMF episodes, and determining the differences in the FMF severity score, acute phase reactants and quality of life between the treatment arms. The significance of the study includes short and long-term benefits. Fewer FMF episodes will result in less functional impairment and a higher quality of life in colchicine resistant or intolerant patients. Once weekly injections have the potential to improve treatment compliance. Fewer acute episodes of arthritis may prevent the development of chronic joint damage. In the long- term, better FMF control may prevent amyloidosis. This study may confirm the importance of IL-1 in the pathogenesis of FMF and provide support for an FDA filing for use of IL-1 Trap in FMF.

描述（由申请人提供）：

项目成果

Enhancing crossover trial design for rare diseases: limiting ineffective exposure and increasing study power by enabling patient choice to escape early.

加强罕见疾病的交叉试验设计：通过让患者选择尽早逃避来限制无效暴露并提高研究能力。

• DOI: 10.1016/j.cct.2014.05.001
• 发表时间: 2014
• 期刊: Contemporary clinical trials
• 影响因子: 2.2
• 作者: Huang,Bin;Giannini,EdwardH;Lovell,DanielJ;Ding,Lili;Liu,Yongchao;Hashkes,PhilipJ
• 通讯作者: Hashkes,PhilipJ