High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial.

Here we assessed the potential for high-dose nusinersen to rapidly slow neurodegeneration and lead to improved outcomes for patients.

在这里，我们评估了高剂量ヌシネルセン迅速减缓神经退行性病变并改善患者预后的潜力。

The global, three-part, phase 2/3 DEVOTE trial evaluated the efficacy and safety of high-dose nusinersen (50-mg loading dose; 28-mg maintenance dose) in individuals with SMA.

全球性的、三部分的DEVOTE试验是一个2/3期研究，评估了高剂量的nusinersen（50-mg负荷剂量；28-mg维持剂量）在脊髓性肌萎缩症（SMA）患者中的疗效和安全性。

In Part B, treatment-naive individuals (n = 75) were randomized 2:1 to 50/28 mg or 12/12 mg nusinersen.

在B部分中，未接受过治疗的患者（n = 75）被随机分为2:1的比例，接受50/28 mg或12/12 mg的nusinersen治疗。

In a supportive open-label cohort (Part C), nusinersen-experienced individuals (12/12 mg for more than 1 year) were enrolled.

在一项支持性的开放标签队列研究（C部分）中，招募了接受nusinersen治疗超过1年的个体（12/12 mg）

The primary endpoint (Part B infantile-onset participants) was a 6-month change in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score comparing 50/28 mg with matched ENDEAR participants (n = 20) who received sham.

主要终点（B部分婴儿发病参与者）是与接受安慰剂的匹配ENDEAR参与者（n = 20）相比，50/28 mg组在6个月内的儿童医院费城神经肌肉障碍测试（CHOP-INTEND）总分的变化。

DEVOTE met its primary endpoint: at day 183, the CHOP-INTEND total score significantly improved (+15.1 points) in those who received 50/28 mg nusinersen and worsened (-11.1 points) in matched ENDEAR participants who received sham (difference, 26.19 (95% confidence interval= 20.7 to 31.74); statistical testing was performed using the joint-rank test where the difference in ranks was 26.06 (95% confidence interval= 17.9 to 34.2; P < 0.0001).

DEVOTE 达到了其主要终点：在第183天，接受50/28 mg nusinersen治疗的患者的CHOP-INTEND总分显著提高了（+15.1分），而在匹配的ENDEAR参与者中，接受安慰剂治疗的患者病情恶化（-11.1分），差异为26.19（95%置信区间=20.7至31.74）；使用联合秩次检验进行统计测试，秩次差异为26.06（95%置信区间=17.9至34.2；P < 0.0001）。

The safety profile of 50/28 mg nusinersen was similar to the 12/12 mg regimen.

50/28 mg nusinersen的安全性特征与12/12 mg方案相似。

The data support that high-dose nusinersen provides benefit in patients with SMA, with a generally well-tolerated safety profile.

数据支持高剂量的nusinersen在脊髓性肌萎缩症（SMA）患者中具有益处，并且具有良好的耐受性安全特性。

ClinicalTrials.gov registration: https://clinicaltrials.gov/study/NCT04089566 .

ClinicalTrials.gov注册信息：https://clinicaltrials.gov/study/NCT04089566 .

EudraCT no: 2019-002663-10.

EudraCT编号：2019-002663-10。