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来自 Pridopidine 治疗亨廷顿病的开放性延展研究(Open-HART)的 48 个月和 60 个月的额外安全性和探索性疗效数据。

Additional Safety and Exploratory Efficacy Data at 48 and 60 Months from Open-HART, an Open-Label Extension Study of Pridopidine in Huntington Disease.

机构信息

Cooper University Health Care at Rowan University, Camden, NJ, USA.

University of Rochester Medical Center, Rochester, NY, USA.

出版信息

J Huntingtons Dis. 2020;9(2):173-184. doi: 10.3233/JHD-190393.

Abstract

BACKGROUND

Open-HART was an open-label extension of HART, a randomized, double-blind, placebo-controlled study of pridopidine in Huntington disease (HD). Previously, we reported safety and exploratory efficacy data after 36 months of treatment with pridopidine 45 mg twice daily. In the interim, emerging data suggests pridopidine may have neuroprotective effects mediated by sigma-1 receptor agonism.

OBJECTIVE

To report additional safety and exploratory efficacy data for continued open-label use of 45 mg BID pridopidine at 48 and 60 months.

METHODS

Patients in Open-HART were followed up to or greater than 60 months. Adverse events, concomitant medications, vital signs, laboratory values, and ECG data were monitored. Rates of decline in total functional capacity (TFC) and total motor score (TMS) over 60 months were evaluated in an exploratory analysis and compared between Open-HART and placebo recipients from the 2CARE trial. To account for missing data, sensitivity analyses were performed.

RESULTS

Of the original Open-HART baseline cohort (N = 118), 40 remained in the study at 48 months and 33 at 60 months. Pridopidine remained safe and well tolerated over the 60-month interval. TFC and TMS at 48 and 60 months remained stable, showing less decline at these timepoints compared to historical placebo controls from the 2CARE trial. TFC differences at 48 and 60 months observed remained nominally significant after sensitivity analysis.

CONCLUSION

The 45 mg BID pridopidine dosage remained safe and tolerable over 60 months. Exploratory analyses show TFC and TMS stability at 48 and 60 months, in contrast to placebo historical controls from the 2CARE trial. Results are consistent with data reported from the recent Phase 2 PRIDE-HD trial showing less functional decline in the pridopidine 45 mg BID treated group at 52 weeks.

摘要

背景

Open-HART 是 HART 的开放性扩展研究,HART 是一项针对亨廷顿病(HD)的随机、双盲、安慰剂对照的普里多吡啶研究。此前,我们报告了普里多吡啶 45mg 每日两次治疗 36 个月后的安全性和探索性疗效数据。在此期间,新出现的数据表明,普里多吡啶可能通过 sigma-1 受体激动作用具有神经保护作用。

目的

报告继续使用普里多吡啶 45mg 每日两次治疗 48 个月和 60 个月的额外安全性和探索性疗效数据。

方法

Open-HART 中的患者随访时间达到或超过 60 个月。监测不良事件、伴随药物、生命体征、实验室值和心电图数据。在探索性分析中评估了 60 个月内总功能能力(TFC)和总运动评分(TMS)的下降率,并与 2CARE 试验中的安慰剂组进行了比较。为了处理缺失数据,进行了敏感性分析。

结果

在原始 Open-HART 基线队列(N=118)中,40 例患者在 48 个月时仍在研究中,33 例在 60 个月时仍在研究中。在 60 个月的时间间隔内,普里多吡啶仍然安全且耐受良好。在 48 个月和 60 个月时,TFC 和 TMS 保持稳定,与 2CARE 试验中的历史安慰剂对照组相比,这些时间点的下降幅度较小。在敏感性分析后,观察到的 48 个月和 60 个月的 TFC 差异仍然具有名义显著性。

结论

45mg 每日两次的普里多吡啶剂量在 60 个月内仍然安全且耐受良好。探索性分析显示,在 48 个月和 60 个月时,TFC 和 TMS 稳定,与 2CARE 试验中的历史安慰剂对照组形成对比。结果与最近的 PRIDE-HD 二期试验报告的数据一致,表明在 52 周时,普里多吡啶 45mg 每日两次治疗组的功能下降幅度较小。

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