A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A (CMT1A) Treated 15 Months
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 176
- 试验地点
- 25
- 主要终点
- Overall Neuropathy Limitation Scale (ONLS) score
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled and multicenter 3 phase trial evaluating the therapeutic effect and safety of CMT1A by PXT3003. This double-blind study will assess in parallel groups 1 dose of PXT3003 compared to Placebo in CMT1A patients treated for 15 months.
详细描述
This multi-center, randomized, double-blind, placebo-controlled, Phase III clinical study is designed to evaluate PXT3003 versus placebo in subjects with genetically confirmed CMT1A of mild-to-moderate severity (CMTNS-V2 score >2 and ≤18) aged 16 to 65 years.
Genetically confirmed CMT1A subjects will be screened and randomized in a 1:1 ratio to receive either oral PXT3003 daily or matching placebo for 15 months. A total of approximately 176 subjects will be enrolled.
Visits will take place at Screening (up to -30 days), Baseline , and Months 3, 6, 9, 12, and 15.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 16 to 65 years (included boundary value), of either sex;
- •Patients with CMT1A (PMP22 duplication on chromosome 17p11.2) confirmed by gene diagnosis; 3.2 < CMTNS-v2 score ≤ 18;
- •4.Patients are dorsalis pedis flexor weakness at least (clinical evaluation); 5.Ulnar nerve motor nerve conductance velocity > 15 m/s; 6.Subjects participate in clinical trials and sign informed consent voluntarily , and they have the ability to understand as will as abide by research procedures.
排除标准
- •Being allergic to RS-baclofen, naltrexone HCL, D-sorbitol or any component in pxt3003 excipients or having other serious prior allergic reaction;
- •Existence contraindications of baclofen, naltrexone or sorbitol, such as porphyria;
- •Any other associated cause of peripheral neuropathy such as diabetes mellitus (including diabetes history and glycosylated hemoglobin >6.5%)
- •Subjects with other neurological diseases affecting the evaluation of study treatment;
- •Patients with the score of ONLS score is 0;
- •A history of unstable medical diseases with clinically significant unstable medical diseases (unstable angina pectoris, tumor, blood disease, hepatitis or liver failure, renal failure, etc.) that may cause harm to the subjects participating in this study in the past 1 year;
- •Limb surgery had implemented within the first six months of randomization or will be planned before the completion of the clinical trial;
- •Hepatic or renal dysfunction:
- •TBIL>1.5×ULN,ALT>3×ULN,AST>3×ULN;
- •Cr>1.5×ULN;
- •Syphilis antibody and HIV antibody positive subjects;
- •Subjects with tumors indicated by chest radiograph or B-ultrasound;
- •Subjects with alcohol dependence in recent 3 months;
- •Females that are of childbearing potential, pregnant, or are breast-feeding;Subjects who are unable to use appropriate contraceptives during the trial;
- •Subjects with concomitant treatment 4 weeks before enrollment, including but not limited to baclofen, naltrexone, sorbitol, opioids, vitamin C, levothyroxine and potentially neurotoxic drugs (such as amiodarone and chloroquine);
- •Subjects unable to complete the follow-up of study;
- •Participated in another clinical trial and used the test drug within the last 30 days;
- •Different subjects from the same family and living in the same residence can only include one subject, so as to avoid treatment confusion, affect blind treatment and affect the interpretation of the research results;
- •Investigators affirm the compliance in a certain subject is poor or there are some other factors that are not suitable to participate in this clinical trial.
研究组 & 干预措施
PXT3003
Liquid oral solution, 10 mL twice a day, morning and evening with food
干预措施: PXT3003 (Drug)
PXT3003 Placebo
Liquid oral solution, 10 mL twice a day, morning and evening with food
干预措施: PXT3003 placebo (Drug)
结局指标
主要结局
Overall Neuropathy Limitation Scale (ONLS) score
时间窗: 15 months
The primary efficacy endpoint will be the main effect of the studied treatment on the improvement of disability measured by the Overall Neuropathy Limitation Scale (ONLS) score, summarized at 15 months defined by: the change of the ONLS from baseline to the 15 months.ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score to measure limitations in the everyday activities of the upper limbs (rated in 5 points) and the lower limbs (rated on 7 points) . The total score goes from 0 ( no disability) to 12 (maximum disability).
次要结局
- Treatment responders rate of PXT3003;(15 months)
- 10-Meter Walk Test (10MWT);(15 months)
- Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side:(15 months)
- The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS)(15 months)
- Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2);(15 months)
- Nine-hole peg test (9HPT) for non-dominant hand ;(15 months)
- Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side(15 months)
- Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ;(15 months)