Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial
Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial
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DOI：
10.1016/s1474-4422(20)30279-9
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发表时间：
2020-10-01
期刊：
影响因子：
48
通讯作者：
Detke, Holland C.
中科院分区：
文献类型：
--
作者：
Mulleners, Wim M.;Kim, Byung-Kun;Detke, Holland C.
背景：许多需要偏头痛预防治疗的患者不能耐受或对以前的多种预防药物没有反应。我们的目标是评估降钙素基因相关肽的抗体Galcanezumab在2-4类预防药物未受益的偏头痛患者中的安全性和有效性。方法Conquer是一项多中心、随机、双盲、安慰剂对照的3b期试验，在12个国家(比利时、加拿大、捷克共和国、法国、德国、匈牙利、日本、荷兰、韩国、西班牙、英国和美国)的网站(医院、诊所或研究中心)进行。患者年龄为18-75岁，有间歇性或慢性偏头痛，偏头痛在50岁之前起病，在过去10年中，由于缺乏疗效或耐受性，或两者兼而有之，有证据表明两种至四种药物预防药物失败。患者被随机分成1：1，每月接受皮下安慰剂或Galcanezumab 120 mg(240 mg负荷量作为两次120 mg注射)，为期3个月。出于掩饰的目的，接受安慰剂的患者在第一次给药期间也接受了两次注射。通过计算机生成的随机序列，通过交互式网络响应系统按国家和偏头痛频率分层(低频率发作性偏头痛，每月4至8天偏头痛；高频发作性偏头痛，每月8至14天偏头痛，每月少于15天头痛；慢性偏头痛，每月至少8天偏头痛，每月至少15天头痛)。主要终点是在3个月的治疗期间，所有被随机分配并接受至少一剂研究药物的患者的每月偏头痛天数与基线相比的总体平均变化。这项试验在ClinicalTrials.gov，NCT03559257注册，现在已经完成。在2018年9月10日至2019年3月21日期间，462名患有发作性(269[58%])或慢性(193[42%])偏头痛的参与者被随机分配，并接受了至少一次注射安慰剂(n=230)或Galcanezumab(n=232)。在1-3个月中，接受Galcanezumab治疗的偏头痛患者比服用安慰剂的患者偏头痛天数减少得更多。与基线相比，Galcanezumab组每月偏头痛天数平均减少4.1天(13.4天)，而安慰剂组平均每月偏头痛天数比基线时减少1.0天(13.0；组间差异-3.1[95%CI-3.9至-2.3]；p
Background Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories.Methods CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). Patients were 18-75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 1:1 to receive subcutaneous placebo or galcanezumab 120 mg per month (with a 240 mg loading dose administered as two 120 mg injections) for 3 months. For masking purposes, patients receiving placebo also received two injections during the first dosing visit. Randomisation was done by a computer-generated random sequence by means of an interactive web-response system stratified by country and migraine frequency (low frequency episodic migraine, four to fewer than eight migraine headache days per month; high frequency episodic migraine, eight to 14 migraine headache days per month and fewer than 15 headache days per month; chronic migraine, at least eight migraine headache days per month and at least 15 headache days per month). The primary endpoint was the overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03559257, and is now completed.Findings Between Sept 10, 2018, and March 21, 2019, 462 participants with episodic (269 [58%]) or chronic (193 [42%]) migraine were randomly assigned and received at least one injection with placebo (n=230) or galcanezumab (n=232). Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1-3. The galcanezumab group had on average 4.1 fewer monthly migraine headache days compared with baseline (13.4), while the placebo group had on average 1.0 fewer than at baseline (13.0; between-group difference -3.1 [95% CI -3.9 to -2.3]; p