Juntas-Morales Raul, Pageot Nicolas, Bendarraz Abdelkarim, Alphandéry Sébastien, Sedel Frédéric, Seigle Stéphanie, Camu William
Clinique du motoneurone, Explorations Neurologiques, CHU Gui de Chauliac, Montpellier, France.
MedDay Pharmaceuticals, Paris, France.
EClinicalMedicine. 2020 Jan 27;19:100254. doi: 10.1016/j.eclinm.2019.100254. eCollection 2020 Feb.
Oligodendrocytes (OGs) provide metabolic support to motor neurons (MNs) and are implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). MD1003, or high-dose Pharmaceutical grade Biotin (hdPB), may improve disability in progressive multiple sclerosis patients via augmentation of OG or MN energy levels. Here, we assessed the safety and efficacy of MD1003 in ALS patients.
This single centre, randomised, double-blind, placebo-controlled trial included patients aged 25-80 years with probable or definite ALS. Patients were assigned (2:1), using a computer-generated randomisation list, to receive oral MD1003 (300 mg/day) or placebo treatment for 24 weeks. The primary outcome, safety, was analysed in all patients who received at least one dose of study drug. This study, registered with ClinicalTrials.gov, NCT03114215, has been completed.
Between June and December 2016, 30 patients were enrolled (MD1003, = 20; placebo, = 10). Baseline characteristics were representative of the ALS population. MD1003 and placebo groups were not well balanced at screening, with the MD1003-treated group having a higher rate of ALSFRS-R decline prior to screening versus placebo (-6·0 IQR [-8·5, -5·0] vs. -5·0 IQR [-5·0, -3·0]) and a predominance of ALS with upper limb onset compared to placebo (35% vs. 10%). MD1003 had a favourable safety profile and was well tolerated. The occurrence of adverse events was similar in both groups (60%). Two deaths occurred in the MD1003 group versus 1 in the placebo group. ALSFRS-R median change from baseline to month 6 was not significantly different between the two groups ( = 0·49); the mean difference between groups was -1·6 (SEM=3·3).
MD1003 treatment was safe and well tolerated. It was not possible to establish MD1003 efficacy in this relatively small study. Given the favourable safety profile of MD1003 and an imbalance between treatment groups favouring placebo, additional, larger studies in ALS are warranted.
MedDay Pharmaceuticals.
少突胶质细胞（OGs）为运动神经元（MNs）提供代谢支持，并与肌萎缩侧索硬化症（ALS）的病理生理学有关。MD1003，即高剂量药用级生物素（hdPB），可能通过提高OG或MN的能量水平来改善进展性多发性硬化症患者的残疾状况。在此，我们评估了MD1003在ALS患者中的安全性和疗效。
这项单中心、随机、双盲、安慰剂对照试验纳入了年龄在25至80岁之间、可能或确诊为ALS的患者。使用计算机生成的随机列表将患者按2:1分配，分别接受口服MD1003（300毫克/天）或安慰剂治疗24周。对所有接受至少一剂研究药物的患者分析主要结局即安全性。本研究已在ClinicalTrials.gov注册，编号为NCT03114215，现已完成。
在2016年6月至12月期间，共招募了30名患者（MD1003组20名；安慰剂组10名）。基线特征代表了ALS患者群体。MD1003组和安慰剂组在筛查时未达到良好的平衡，MD1003治疗组在筛查前ALSFRS-R下降率高于安慰剂组（-6.0四分位间距[-8.5, -5.0]对-5.0四分位间距[-5.0, -3.0]），且与安慰剂组相比，上肢起病的ALS患者占比更高（35%对10%）。MD1003具有良好的安全性，耐受性良好。两组不良事件的发生率相似（60%）。MD1003组有2例死亡，安慰剂组有1例死亡。两组从基线到第6个月时ALSFRS-R的中位数变化无显著差异（P = 0.49）；组间平均差异为-1.6（标准误=3.3）。
MD1003治疗安全且耐受性良好。在这项相对较小的研究中无法确定MD1003的疗效。鉴于MD1003良好的安全性以及治疗组间偏向安慰剂的不平衡性，有必要在ALS患者中开展更多、更大规模的研究。
MedDay制药公司。
