Department of Pediatrics, Peking University First Hospital, No.1, Xi'an Men Street, West District, Beijing, 100034, China.
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Orphanet J Rare Dis. 2020 Sep 14;15(1):248. doi: 10.1186/s13023-020-01530-5.
This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).
A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson's Disease Rating Scale (UPDRS) I-III and Fahn-Marsden (FM) score from baseline to week 24 after treatment.
Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60 mg/kg per day, there was no difference in either UPDRS I-III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as "slightly improved" by doctors through blinded video assessment. Patients with lower baseline UPDRS I-III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study.
Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day.
Clinical trial registration number at www.chictr.org.cn :ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered.
本研究旨在探讨泛酰巯基乙胺（pantethine）治疗泛酸激酶相关神经变性（PKAN）患儿的疗效和安全性。
本研究为单臂、开放标签研究。所有受试者在 24 周的治疗期间接受泛酰巯基乙胺治疗。主要终点为治疗后 24 周时统一帕金森病评定量表（UPDRS）Ⅰ-Ⅲ和 Fahn-Marsden（FM）评分与基线相比的变化。
共纳入 15 例 PKAN 患儿，所有患者均完成了研究。在每天 60mg/kg 的泛酰巯基乙胺治疗 24 周后，UPDRS Ⅰ-Ⅲ评分（t=0.516，P=0.614）或 FM 评分（t=0.353，P=0.729）与基线相比均无差异。然而，UPDRS Ⅰ-Ⅲ评分（Z=2.614，p=0.009）和 FM 评分（Z=2.643，p=0.008）的增加率均有所减缓。通过盲法视频评估，有 4 名（26.7%）患者被医生评估为“略有改善”。基线 UPDRS Ⅰ-Ⅲ或 FM 评分较低的患者更有可能改善。患者治疗后，通过 PedsQL TM 2.0 FIM 评分评估，其家属的生活质量得到改善，而患者在 W24 时的生活质量通过 PedsQL TM 4.0 和 PedsQL TM 3.0 NMM 评估则保持不变。治疗前后血清 CoA 水平无差异。研究期间无药物相关不良事件发生。
在 24 周治疗后，泛酰巯基乙胺不能显著改善 PKAN 患儿的运动功能，但可能延缓运动功能障碍的进展。每天 60mg/kg 的泛酰巯基乙胺耐受性良好。
www.chictr.org.cn 临床试验注册号：ChiCTR1900021076，注册于 2019 年 1 月 27 日，首位入组患者于 2018 年 9 月 30 日入组，其余 14 名患者在试验注册后入组。
