Department of Neurology, Faculty of Medicine, CHU de Reims, URCA, Reims, France.
LPN EA 2027, Université Paris 8, Saint-Denis, France.
CNS Drugs. 2018 Jul;32(7):661-672. doi: 10.1007/s40263-018-0528-2.
Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS.
The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss.
The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed.
Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (- 0.061 logMAR, + 3.1 letters) than with placebo (- 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (- 0.058 logMAR) with MD1003 and worsened by - 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo.
MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated.
EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals.
慢性视力丧失是多发性硬化症（MS）患者的致残特征。最近的研究表明，MD1003（高剂量医药级生物素或 hdPB）可能改善进展性 MS 患者的残疾状况。
本研究旨在评估 MD1003 是否比安慰剂改善 MS 慢性视力丧失患者的视力。
MS-ON 是一项为期 6 个月的随机、双盲、安慰剂对照研究，具有 6 个月的开放标签扩展阶段。患有 MS 相关慢性视力丧失的成年患者（至少一眼视力低于 0.5 十进制图表），按 2:1 的比例随机分配接受口服 MD1003 300mg/天或安慰剂。所选眼必须在过去 3 年内出现急性视神经炎（AON）或缓慢进展性视神经病变（PON）后出现视力恶化。主要终点是所选眼在 100%对比度下测量的对数最小角度分辨率（logMAR）的基线至第 6 个月的平均变化。还评估了视觉诱发电位、视野、视网膜神经纤维层（RNFL）厚度和健康结果。
93 名患者接受了 MD1003（n=65）或安慰剂（n=28）治疗。该研究未达到其主要终点，因为主要终点的平均变化无显著差异（p=0.66），MD1003（-0.061 logMAR，+3.1 个字母）大于安慰剂（-0.036 logMAR，+1.8 个字母）。预先计划的亚组分析表明，MD1003 治疗组患者的 100%对比度 VA 平均改善了+2.8 个字母（-0.058 logMAR），而安慰剂治疗组患者的 VA 恶化了-1.5 个字母（+0.029 logMAR）（p=0.45）。在 PON 患者亚组中，MD1003 治疗组患者的 5%对比度 logMAR、RNFL 厚度和健康结果评分也有非显著性改善。在 AON 患者中，MD1003 与安慰剂相比没有优势。MD1003 的安全性与安慰剂相似。
与安慰剂相比，MD1003 并未显著改善慢性视力丧失 MS 患者的视力。在 PON 患者亚组中观察到有利于 MD1003 的有趣趋势。总体而言，治疗耐受性良好。
EudraCT 标识符 2013-002112-27。临床试验.gov 标识符：NCT02220244 资金来源：MedDay 制药公司。
