International, Multi-center, Open Label, Follow-up Extension Study Assessing the Long-term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 187
- 试验地点
- 23
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
研究概览
简要总结
All randomised patients with Charcot-Marie-Tooth Type 1A (CMT1A) who completed the primary study CLN-PXT3003-02, i.e. treatment with PXT3003 or placebo, are eligible to continue in the extension study CLN-PXT3003-03.
Period 1: Patients randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL).
Period 2: All patients continue on twice dose 1 (2X5mL).
详细描述
PXT3003 is a rational design, fixed combination of low-dose (RS) baclofen, naltrexone hydrochloride and D-sorbitol. The use of PXT3003 in a multicenter, randomised, placebo controlled phase II study (CLN-PXT3003-01) was well-tolerated and safe in patients with CMT1A for the three dose-levels investigated (Attarian et al., 2014). The intermediate and high dose of PXT3003 demonstrated an improvement of disability in this patient population.
Subsequently a multicenter, randomised, placebo controlled phase III study (CLN-PXT3003-02) to assess the efficacy and safety of PXT3003 in the treatment of patients with CMT1A was initiated in December 2015. In March 2017 the first patients completed the 15-month treatment with PXT3003 and rolled over into the extension study CLN-PXT3003-03.
During Period 1 (9 months), patients that were randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL). During Period 2, all patients continue on twice dose 1 (2X5mL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 67 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Any clinically significant change in health status that, in the opinion of the Investigator, would prevent the subject from participating in this study or successfully completing this study
- •Any unauthorized concomitant treatments, as study CLN-PXT3003-02 (e.g. including but not limited to baclofen, naltrexone,sorbitol (pharmaceutical form), opioids, levothyroxin, and potentially neurotoxic drugs such as amiodarone, chloroquine, cancer drugs susceptible to induce peripheral neuropathy)
研究组 & 干预措施
PXT3003 dose 1
Period 1, PXT3003 : Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months
干预措施: PXT3003 (Drug)
PXT3003 dose 2
Period 1, PXT3003: Liquid oral solution (1.2 mg/mL baclofen, 0.14 mg/mL naltrexone HCl and 420 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months
Period 2, PXT3003: Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 10 mL bid (taken morning and evening with food)
干预措施: PXT3003 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
时间窗: 9 or 24 months
Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
次要结局
- Nine-hole Peg Test (9-HPT)(9 or 24 months)
- Incidence of adverse events leading to withdrawal of study drug(9 or 24 months)
- Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items(9 or 24 months)
- Time to walk 10 meters(9 or 24 months)
- Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome(9 or 24 months)
- Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items(9 or 24 months)
- Compound Muscle Action Potential (CMAP) on ulnar nerve(9 or 24 months)
- Nerve conduction velocity (NCV)(9 or 24 months)
- Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)(9 or 24 months)
- Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)(9 or 24 months)
- Sensory Nerve Action Potential (SNAP) on radial nerve(9 or 24 months)
- Quality of Life (EQ-5D)(9 or 24 months)