A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention.
A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention.
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DOI：
10.1177/0333102420970889
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Mikol DD
中科院分区：
文献类型：
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作者：
Ashina M;Doležil D;Bonner JH;Zhou L;Klatt J;Picard H;Mikol DD
目的：评价垂体腺苷环化酶激活多肽(PACAP)-1(PAC1)受体抑制剂AMG 301预防偏头痛的安全性和有效性。在一项双盲试验中，患者被随机分为4：3：3的安慰剂，每4周服用AMG 301 210 mg，或每2周服用AMG 301 420 mg，为期12周。在9-12周内评估对每月偏头痛天数和其他辅助措施的影响。评估安全性和耐受性。在343名随机分组的患者中(平均年龄41.8-42.5岁)，大多数是女性(85.4-90.4%)，白人(94.1-96.2%)，并有发作性偏头痛(62.5-67.9%)。共有305名患者完成治疗(安慰剂，n = 124；AMG301210 mg，n = 94；AMG301420 mg，n = 87)。12周时，两个AMG301治疗组的每月偏头痛天数较基线的最小二乘平均减少分别为−2.5d(0.4d)和−2.2d(0.5d)。没有观察到AMG301和安慰剂在任何疗效指标上的差异；AMG301210 mg和安慰剂每月偏头痛天数的平均治疗差异(95%可信区间)，0.3(−0.9至1.4)；AMG301420 mg，0.3(−0.9至1.4)。不同组别的不良事件发生率相似。在偏头痛预防方面，AMG301与安慰剂相比没有好处；可能需要进一步研究，以充分了解PACAP异构体及其受体在偏头痛病理生理学中的作用。ClinicalTrials.gov：NCT03238781
To assess the safety and efficacy of AMG 301, an inhibitor of the pituitary adenylate cyclase-activating polypeptide (PACAP)-1 (PAC1) receptor, for prevention of migraine. In a double-blind trial, patients were randomized 4:3:3 to placebo, AMG 301 210 mg every 4 weeks, or AMG 301 420 mg every 2 weeks for 12 weeks. Effect on monthly migraine days and other secondary measures were assessed over weeks 9–12. Safety and tolerability were assessed. Of 343 randomized patients (mean age, 41.8–42.5 years), the majority were women (85.4–90.4%), white (94.1–96.2%), and had episodic migraine (62.5–67.9%). A total of 305 patients completed treatment (placebo, n = 124; AMG 301 210 mg, n = 94; AMG 301 420 mg, n = 87). Least squares mean reduction at week 12 in monthly migraine days from baseline was −2.5 (0.4) days for placebo and −2.2 (0.5) days for both AMG 301 treatment groups. No difference between AMG 301 and placebo on any measure of efficacy was observed; mean (95% confidence interval) treatment difference versus placebo for monthly migraine days for AMG 301 210 mg, 0.3 (−0.9 to 1.4); AMG 301 420 mg, 0.3 (−0.9 to 1.4). The incidence of adverse events was similar across groups. AMG 301 offered no benefit over placebo for migraine prevention; further studies may be necessary to fully understand the role of PACAP isoforms and its receptors in migraine pathophysiology. ClinicalTrials.gov: NCT03238781