瑞加巴林（HSK16149）用于成人带状疱疹后神经痛的疗效和安全性：一项3期随机临床试验
Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial.
作者信息
Zhang Daying, Lei Tiechi, Qin Lanying, Li Chenyu, Lin Xuewu, Wang Huiping, Zhang Guoqiang, Zhang Shoumin, Shi Kemei, Li Linfeng, Yang Zhenling, Yang Xiumin, Ba Xiaohong, Gao Ying, Zhang Zhuobo, Wang Guonian, Wu Liming, Wang Yaping, Wang Yu, Zhu Shoumin, Shi Jihai, Ye Zhijian, Yang Chunjun, Liu Changyi, Zhang Tong, Lu Shousi, Yu Nan, Li Xiangkui, Han Xiuping, Chen Xiaoyan, Wan Li, Cheng Zhigang, Bai Nianyue, Jin Zhehu, Yu Chunshui, Zhang Weiyi, Lu Jianyun, Wang Dongmei, Sun Hui, Wu Wenzhong, Qin Pingping, Feng Zhiying, Chen Rixin, Zhang Tangde, Yang Dong, Yin Wenhao, Zhang Jianglin, Li Xin, Li Fangqiong, Wu Tingting, Lu Qianjin
机构信息
Department of Pain Medicine, The First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China.
Department of Dermatology, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, Hubei, China.
出版信息
JAMA Dermatol. 2024 Nov 1;160(11):1182-1191. doi: 10.1001/jamadermatol.2024.3410.
IMPORTANCE
China carries a heavy burden of postherpetic neuralgia, with an unmet need for novel drugs with greater efficacy and less prominent neurotoxic effects than existing calcium channel ligands.
OBJECTIVE
To investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, carried out between November 9, 2021, and January 5, 2023, at 48 tertiary care centers across China had 2 parts. Part 1 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisting of a 2-week screening period, a 7-day run-in period, and a 12-week double-blind treatment period. Part 2 was a 14-week open-label extension study. Investigators, statisticians, trial clinicians, and patients were blinded to trial group assignments. Participants included adults with postherpetic neuralgia with an average daily pain score (ADPS) of at least 4 on the 11-point Numeric Pain Rating Scale over the preceding week, with the exclusion of patients with pain not controlled by prior therapy with pregabalin (≥300 mg/d) or gabapentin (≥1200 mg/d).
INTERVENTIONS
Patients were randomized 1:1:1 to receive crisugabalin, 20 mg twice daily (ie, 40 mg/d), and crisugabalin, 40 mg twice daily (ie, 80 mg/d), or placebo for 12 weeks. Eligible patients received crisugabalin, 40 mg, twice daily during extension.
MAIN OUTCOME AND MEASURE
The primary efficacy end point was the change from baseline in ADPS at week 12.
RESULTS
The study enrolled 366 patients (121 patients receiving crisugabalin, 40 mg/d; 121 patients receiving crisugabalin, 80 mg/d; 124 patients receiving placebo; median [IQR] age, 63.0 [56.0-69.0] years; 193 men [52.7%]). At week 12, the least squares mean (SD) change from baseline in ADPS was -2.2 (0.2) for crisugabalin, 40 mg/d, and -2.6 (0.2) for crisugabalin, 80 mg/d, vs -1.1 (0.2) for placebo, with a least squares mean difference of -1.1 (95% CI, -1.6 to -0.7; P < .001) and -1.5 (-95% CI, -2.0 to -1.0; P < .001) vs placebo, respectively. No new safety concerns emerged.
CONCLUSIONS AND RELEVANCE
Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05140863.
重要性
中国带状疱疹后神经痛负担沉重，对疗效更佳且神经毒性比现有钙通道配体更不显著的新型药物存在未满足的需求。
目的
研究口服钙通道α2δ-1亚基配体曲西加巴林治疗带状疱疹后神经痛的疗效和安全性。
设计、地点和参与者：这项随机临床试验于2021年11月9日至2023年1月5日在中国48家三级医疗中心进行，分为两部分。第1部分是一项3期、多中心、随机、双盲、安慰剂对照、平行组研究，包括2周的筛查期、7天的导入期和12周的双盲治疗期。第2部分是一项14周的开放标签扩展研究。研究人员、统计学家、试验临床医生和患者对试验组分配情况不知情。参与者包括带状疱疹后神经痛成人患者，其在之前一周的11点数字疼痛评分量表上的平均每日疼痛评分（ADPS）至少为4分，排除先前使用普瑞巴林（≥300 mg/天）或加巴喷丁（≥1200 mg/天）治疗疼痛未得到控制的患者。
干预措施
患者按1:1:1随机分组，接受曲西加巴林，每日两次，每次20 mg（即40 mg/天），或曲西加巴林，每日两次，每次40 mg（即80 mg/天），或安慰剂，为期12周。符合条件的患者在扩展期接受曲西加巴林，每日两次，每次40 mg。
主要结局和测量指标
主要疗效终点是第12周时ADPS相对于基线的变化。
结果
该研究共纳入366例患者（121例接受40 mg/天曲西加巴林治疗；121例接受80 mg/天曲西加巴林治疗；124例接受安慰剂治疗；年龄中位数[四分位间距]为63.0[56.0 - 69.0]岁；193例男性[52.7%]）。在第12周时，40 mg/天曲西加巴林组ADPS相对于基线的最小二乘均值（标准差）变化为 -2.2（0.2），80 mg/天曲西加巴林组为 -2.6（0.2），而安慰剂组为 -1.1（0.2），与安慰剂相比，最小二乘均值差异分别为 -1.1（95%置信区间，-1.6至 -0.7；P <.001）和 -1.5（95%置信区间，-2.0至 -1.0；P <.001）。未出现新的安全问题。
结论和相关性
40 mg/天或80 mg/天的曲西加巴林耐受性良好，与安慰剂相比，ADPS有统计学显著改善。
试验注册
ClinicalTrials.gov标识符：NCT05140863。
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