We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619.

中文翻译：

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Domagrozumab 在杜氏肌营养不良症中的随机 2 期试验和开放标签扩展

我们报告了一项 2 期、随机、双盲、2 期试验（每次 48 周）的结果，该试验在杜氏肌营养不良症 (DMD) 患者中进行了多马珠单抗及其开放标签扩展。在 120 名患有 DMD 的门诊男孩（6 至 <16 岁）中，80 名接受了多次递增剂量（5、20 和 40 毫克/千克）多马珠单抗治疗，40 名接受安慰剂治疗。主要终点是安全性和第 49 周 4 级爬坡 (4SC) 时间的平均变化。次要终点包括其他功能测试、药代动力学和药效学。在 domagrozumab 和安慰剂治疗的患者中，平均 (SD) 年龄分别为 8.4 (1.7) 和 9.3 (2.3) 岁。在第 49 周，多马格珠单抗与安慰剂相比，4SC 中平均 (95% CI) 变化与基线的差异为 0.27 (-7.4 至 7.9) 秒 (p = 0.94)。在任何次要临床终点方面没有显着的组间差异。大多数患者在前 48 周内发生≥1 次不良事件；大多数是轻微的，与治疗无关。在每个剂量水平内，多马格珠单抗的中位血清浓度随给药剂量而增加。在 domagrozumab 与安慰剂治疗的患者中观察到肌肉体积的非显着增加。Domagrozumab 在 DMD 患者中通常是安全且耐受性良好的。疗效措施不支持显着的治疗效果。Clinicaltrials.gov 标识符：NCT02310763 和 NCT02907619。在 domagrozumab 与安慰剂治疗的患者中观察到肌肉体积的非显着增加。Domagrozumab 在 DMD 患者中通常是安全且耐受性良好的。疗效措施不支持显着的治疗效果。Clinicaltrials.gov 标识符：NCT02310763 和 NCT02907619。在 domagrozumab 与安慰剂治疗的患者中观察到肌肉体积的非显着增加。Domagrozumab 在 DMD 患者中通常是安全且耐受性良好的。疗效措施不支持显着的治疗效果。Clinicaltrials.gov 标识符：NCT02310763 和 NCT02907619。