Eli Lilly and Company, Indianapolis, IN, USA.
Eli Lilly and Company, Erl Wood Manor, Windlesham, UK.
Osteoarthritis Cartilage. 2018 Dec;26(12):1609-1618. doi: 10.1016/j.joca.2018.08.019. Epub 2018 Sep 18.
This study tested whether galcanezumab, a humanized monoclonal antibody with efficacy against migraine, was superior to placebo for the treatment of mild or moderate osteoarthritis (OA) knee pain.
In a multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for 16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks, twice. The primary outcome was change from baseline at Week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by 100 mm visual analog scale (VAS). The trial was considered positive if ≥1 dose of galcanezumab demonstrated ≥95% Bayesian posterior probability of superiority to placebo and ≥50% posterior probability of superiority to placebo by ≥9 mm. A planned interim analysis allowed termination of the study if posterior probability of superiority to placebo by ≥9 mm was ≤5%. Secondary endpoints included WOMAC function subscore and Patient Global Assessment (PGA) of OA. Safety and tolerability were also assessed.
The study was terminated after interim analysis suggested inadequate efficacy. Celecoxib significantly reduced WOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified success criteria. No improvement in any secondary objective was observed. Galcanezumab was well tolerated by OA patients.
This study failed to demonstrate sufficient statistical evidence that galcanezumab was efficacious for treating OA knee pain.
NCT02192190.
本研究旨在测试 galcanezumab（一种对偏头痛有效的人源化单克隆抗体）是否优于安慰剂治疗轻中度骨关节炎（OA）膝关节疼痛。
在一项多中心、双盲、安慰剂对照和塞来昔布对照试验中，中度至重度 OA 疼痛患者被随机分配至安慰剂组；塞来昔布 200mg 每日治疗 16 周；或 galcanezumab 5、50、120 和 300mg 皮下每 4 周 2 次。主要终点为第 8 周时 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）疼痛子评分的变化，采用 100mm 视觉模拟量表（VAS）进行测量。如果 galcanezumab 的至少 1 个剂量显示出优于安慰剂的 95%贝叶斯后验概率≥95%，并且优于安慰剂的后验概率≥50%且≥9mm，则认为试验阳性。计划的中期分析允许如果优于安慰剂的后验概率≤5%，则终止研究。次要终点包括 WOMAC 功能子评分和患者整体评估（PGA）OA。还评估了安全性和耐受性。
中期分析提示疗效不足，研究因此终止。塞来昔布与安慰剂相比显著降低 WOMAC 疼痛子评分[-12.0mm；95%置信区间（CI）-23 至-2mm]。galcanezumab 的任何剂量组均未显示出有临床意义的改善（范围：1.5 至-5.0mm）或符合预定的成功标准。任何次要终点均未观察到改善。OA 患者对 galcanezumab 耐受良好。
本研究未能证明 galcanezumab 治疗 OA 膝关节疼痛具有足够的统计学证据。
NCT02192190。
