加巴喷丁治疗发作性偏头痛的 3 期、随机、双盲、安慰剂对照 PERSIST 研究。
Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study.
机构信息
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
出版信息
J Headache Pain. 2022 Jul 28;23(1):90. doi: 10.1186/s10194-022-01458-0.
BACKGROUND
Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia.
METHODS
This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.
RESULTS
In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo).
CONCLUSIONS
Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.
背景
降钙素基因相关肽结合人源化单克隆抗体加奈珠单抗在先前的 3 期临床试验中已显示出对发作性偏头痛患者的疗效和良好耐受性。我们报告了 PERSIST 研究的结果，该研究旨在评估加奈珠单抗在中国、印度和俄罗斯发作性偏头痛患者中的疗效和安全性。
方法
这是一项在中国（n=26）、印度（n=10）和俄罗斯（n=4）的 40 个中心进行的 3 期研究。符合条件的成年发作性偏头痛患者按 1:1 比例随机接受每月加奈珠单抗 120mg（有 240mg 负荷剂量）或安慰剂治疗，为期 3 个月的双盲治疗期。主要终点是从基线到每月偏头痛头痛天数（MHDs）的总体平均变化。关键次要终点是 MHDs 从基线降低≥50%、≥75%和 100%的患者比例以及偏头痛特异性生活质量问卷（MSQ）角色功能受限领域评分的平均变化。
结果
共有 520 名患者随机接受了至少一剂加奈珠单抗（n=261）或安慰剂（n=259）。与安慰剂相比，加奈珠单抗治疗 3 个月后每月 MHDs 的最小二乘（LS）均值从基线的降低显著更大（-3.81 天与-1.99 天；p<0.0001）。与安慰剂相比，接受加奈珠单抗治疗的患者中，MHDs 从基线降低≥50%、≥75%和 100%的比例显著更高（均 p<0.0001）。与安慰剂相比，加奈珠单抗治疗 3 个月后 MSQ 角色功能受限领域评分的总体平均改善从基线显著更大（p<0.0001）。除注射部位瘙痒（5.0%比 0.0%）、注射部位反应（3.8%比 0.4%）和注射部位不适（2.3%比 0.0%）发生率较高外，加奈珠单抗组与安慰剂组之间在任何安全性参数上均无临床意义上的差异。注射部位相关的 TEAEs 严重程度均为轻度，除 1 例患者出现中度注射部位反应外。6 例严重不良事件由 6 例患者报告（2 例加奈珠单抗，4 例安慰剂）。
结论
每月一次加奈珠单抗 120mg 对来自中国、印度和俄罗斯的发作性偏头痛患者有效且耐受性良好。
试验注册
ClinicalTrials.gov 标识符 NCT03963232（PERSIST），于 2019 年 5 月 24 日注册。
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