Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study
Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study
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DOI：
10.1016/s1474-4422(15)00249-5
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发表时间：
2015-11-01
期刊：
影响因子：
48
通讯作者：
Lipton, Richard B.
中科院分区：
文献类型：
--
作者：
Bigal, Marcelo E.;Dodick, David W.;Lipton, Richard B.
降钙素基因相关肽（CGRP）是治疗发作性偏头痛的有效靶点。在这里，我们评估TEV-48125（一种单克隆抗cgrp抗体）预防性治疗高频发作性偏头痛的安全性、耐受性和有效性。在这项多中心、随机、双盲、安慰剂对照的2b期研究中，我们招募了来自美国62个地点、每月有8-14天偏头痛的男性和女性（年龄18-65岁）。使用由中央计算机系统和交互式网络响应系统生成的随机列表，我们在28天的磨合期后将患者随机分配（1:1，按性别和使用伴随预防药物分层）到三个28天的治疗周期，分别为皮下225 mg TEV-48125、675 mg TEV-48125或安慰剂。研究者、患者和资助者对治疗分配不知情。患者每天使用电子日记报告头痛信息。主要终点是第三个治疗周期（9-12周）偏头痛天数与基线的变化以及安全性和耐受性。次要终点是9-12周头痛天数相对于基线的变化。对意向治疗人群的疗效终点进行分析。安全性和耐受性采用描述性统计分析。该试验已在ClinicalTrials.gov注册，编号NCT02025556。在2014年1月8日至2014年10月15日期间，我们招募了297名参与者：104名随机分配接受安慰剂，95名接受225 mg TEV-48125, 96名接受675 mg TEV-48125。从基线到第9-12周，安慰剂组偏头痛天数的最小二乘平均值（LSM）变化为-3.46天（SD 5.40）， 225 mg剂量组为-6.27天（SD 5.38）， 675 mg剂量组为-6.09天（SD 5.22）。安慰剂组和225 mg剂量组偏头痛天数减少的LSM差异为-2.81天(95% CI为-4.07至-1.55
Background Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine.Methods In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14 days per month. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1: 1: 1; stratified by sex and use of concomitant preventive drugs) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125, 675 mg TEV-48125, or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Patients reported headache information daily using an electronic diary. Primary endpoints were change from baseline in migraine days during the third treatment cycle (weeks 9-12) and safety and tolerability. The secondary endpoint was change relative to baseline in headache-days during weeks 9-12. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered at ClinicalTrials.gov, number NCT02025556.Findings Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants: 104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125, and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number of migraine-days from baseline to weeks 9-12 was -3.46 days (SD 5.40) in the placebo group, -6.27 days (5.38) in the 225 mg dose group, and -6.09 days (5.22) in the 675 mg dose group. The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days (95% CI -4.07 to -1.55; p