OBJECTIVE To investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann-Pick disease type C (NPC) patients. METHODS In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. RESULTS 33 subjects aged 7-64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. CONCLUSIONS NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. CLINICALTRIALS. GOV IDENTIFIER NCT03759639.

中文翻译：

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N-乙酰基-L-亮氨酸在 Niemann-Pick 病 C 型中的疗效和安全性。

目的 研究 N-乙酰-L-亮氨酸 (NALL) 对儿科（≥ 6 岁）和成人 Niemann-Pick 病 C 型 (NPC) 患者的症状、功能和生活质量的安全性和有效性。方法 在这项多国、开放标签、评估者盲法 II 期研究中，患者在基线期、6 周治疗期（≥13 岁的患者口服 NALL 4 g/天，体重分级剂量对于 6-12 岁的患者）和 6 周的治疗后清除期。严重程度变化的主要临床印象 (CI-CS) 终点（基于 7 点李克特量表）由盲法集中评估者评估，他们比较执行预定义的主要锚点测试的每位患者的随机视频对 (8-在每个研究期间进行仪表步行测试或 9 孔钉测试）。次要结果包括小脑功能评定量表、临床总体印象和生活质量评估。结果 33 名年龄在 7-64 岁、确诊为鼻咽癌的受试者入组。32 名患者被纳入主要改良意向治疗分析。NALL 达到了 CI-CS 主要终点（平均差 0.86，SD = 2.52，90% CI 0.25，1.75，p = 0.029）以及次要终点。未发生与治疗相关的严重不良事件。结论 NALL 在 6 周内表现出在症状、功能和生活质量方面具有统计学意义和临床意义的改善，其临床效果在 6 周清除期后丧失。NALL 是安全且耐受性良好的，为 NPC 的治疗提供了有利的收益风险概况。临床试验。政府识别码 NCT03759639。