背景:少突胶质细胞(OGs)为运动神经元(MN)提供代谢支持,并参与肌萎缩侧索硬化(ALS)的病理生理学。MD1003,或高剂量制药级生物素(hdPB),可能通过增加OG或MN能量水平来改善进行性多发性硬化症患者的残疾。这里,我们评估了MD1003在ALS患者中的安全性和有效性.
方法:这个单一的中心,随机化,双盲,安慰剂对照试验纳入年龄在25~80岁的可能或明确的ALS患者.患者被分配(2:1),使用计算机生成的随机化列表,接受口服MD1003(300mg/天)或安慰剂治疗24周。主要结果,安全,在接受至少一剂研究药物的所有患者中进行分析。这项研究,在ClinicalTrials.gov注册,NCT03114215已经完成。
结果:在2016年6月至12月之间,招募了30名患者(MD1003,n=20;安慰剂,n=10)。基线特征代表ALS群体。MD1003组和安慰剂组在筛选时没有很好地平衡,与安慰剂相比,MD1003治疗组在筛查前的ALSFRS-R下降率更高(-6·0IQR[-8·5,-5·0]vs.-5·0IQR[-5·0,-3·0])和与安慰剂相比,上肢发作的ALS占优势(35%vs.10%)。MD1003具有良好的安全性,耐受性良好。两组的不良事件发生率相似(60%)。MD1003组发生2例死亡,安慰剂组发生1例死亡。从基线到第6个月,ALSFRS-R的中位数变化在两组之间没有显着差异(p=0·49)。组间平均差异为-1·6(SEM=3·3)。
结论:MD1003治疗安全且耐受性良好。在这项相对较小的研究中不可能建立MD1003功效。考虑到MD1003的良好安全性和支持安慰剂的治疗组之间的不平衡,额外,有必要对ALS进行更大规模的研究.
背景:MedDay制药。
BACKGROUND: 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.
METHODS: 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.
RESULTS: Between June and December 2016, 30 patients were enrolled (MD1003, n = 20; placebo, n = 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 (p = 0·49); the mean difference between groups was -1·6 (SEM=3·3).
CONCLUSIONS: 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.
BACKGROUND: MedDay Pharmaceuticals.