一项评估 AMG 301（一种垂体腺苷酸环化酶激活多肽 PAC1 受体单克隆抗体）预防偏头痛的 2 期、随机、双盲、安慰剂对照试验。

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.

机构信息

Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Prague Headache Center, DADO MEDICAL sro, Prague, Czech Republic.

出版信息

Cephalalgia. 2021 Jan;41(1):33-44. doi: 10.1177/0333102420970889. Epub 2020 Nov 24.

DOI:10.1177/0333102420970889

PMID:33231489

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7786389/

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

STUDY REGISTRATION

ClinicalTrials.gov: NCT03238781.

摘要

目的

评估垂体腺苷酸环化酶激活肽（PACAP）-1（PAC1）受体抑制剂 AMG 301 预防偏头痛的安全性和有效性。

方法

在一项双盲试验中，患者以 4:3:3 的比例随机分为安慰剂组、AMG 301 210 mg 每 4 周组和 AMG 301 420 mg 每 2 周组，共 12 周。在第 9-12 周评估每月偏头痛天数和其他次要指标的变化。评估安全性和耐受性。

结果

343 名随机患者（平均年龄 41.8-42.5 岁）中，大多数为女性（85.4-90.4%）、白人（94.1-96.2%）和偶发性偏头痛（62.5-67.9%）。共有 305 名患者完成了治疗（安慰剂组 124 例，AMG 301 210 mg 组 94 例，AMG 301 420 mg 组 87 例）。与基线相比，治疗 12 周时每月偏头痛天数的最小二乘均值变化，安慰剂组为-2.5（0.4）天，AMG 301 两组治疗组均为-2.2（0.5）天。AMG 301 与安慰剂在任何疗效评估指标上均无差异；AMG 301 210 mg 与安慰剂相比，每月偏头痛天数的平均（95%置信区间）治疗差异为 0.3（-0.9 至 1.4）；AMG 301 420 mg 为 0.3（-0.9 至 1.4）。不良事件的发生率在各组间相似。