A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pridopidine in Participants With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 60
- 主要终点
- Change from baseline through Week 26 and Week 48 in the Revised ALS Functional Rating Scale (ALSFRS-R) total score adjusted for mortality
研究概览
简要总结
The goal of this clinical trial is to learn if the drug pridopidine works to treat amyotrophic lateral sclerosis in adults. It will also help to learn about the safety of pridopidine. The main question it aims to answer is:
Does pridopidine slow disease progression of ALS?
Researchers will compare pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works to treat ALS.
Participants will:
Take pridopidine or a placebo by mouth every day for 48 weeks. Afterwards, all participants will take pridopidine for another 48 weeks.
Visit the clinic once every 1-3 months for checkups and tests
详细描述
This is a Phase 3, randomized study consisting of a double-blind placebo-controlled (DBPC) period followed by an open-label extension (OLE) to evaluate the efficacy and safety of pridopidine administered orally at a dose of 45 mg twice a day in adult participants with early and rapidly progressing ALS. Standard of care treatments (e.g. riluzole, edaravone and Nuedexta) will be allowed as long as participants are on a stable dose for at least 4 weeks prior to dosing. In the DBPC period, participants will be randomized in a 3:2 ratio to the pridopidine and placebo arms.
In the DBPC period, participants will receive pridopidine or placebo for 48 weeks. In the OLE period, all participants will receive pridopidine for 48 weeks, while maintaining the blind to their original randomization for both the participant as well as the Investigator and other clinical staff. The total study duration per participant will be 102 weeks including screening and follow up.
Throughout the study, participants will be assessed through on-site clinic visits and virtual visits (via telephone).
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Definite ALS or Probable ALS using the El Escorial criteria.
- •Symptom onset of ≤18 months at screening.
- •Slow vital capacity (SVC) greater or equal to 60% predicted.
- •Treatment Research Initiative to Cure ALS (TRICALS) Risk Profile Calculator score, based on the European Network for the Cure of ALS (ENCALS) survival prediction model, in the range of -6 to -2, inclusive, at screening.
- •Able to swallow a capsule.
排除标准
- •Presence of tracheostomy or permanent assisted ventilation.
- •Clinically significant heart disease, clinically significant history of arrhythmia, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, or presence of left bundle branch block.
- •Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent and participate in the study.
- •Clinically significant and/or unstable medical condition (other than ALS) that may either pose a clinically meaningful risk to the participant and/or to study completion.
- •Use of medications that prolong QT interval.
- •Previous treatment with pridopidine, gene therapy, or antisense oligonucleotides.
- •Confirmed mutation in the SOD1, FUS or C9orf72 gene.
- •Pregnancy.
研究组 & 干预措施
Placebo
Placebo hard gelatin capsules. During titration period 1 capsule taken orally in the morning for 2 weeks. During the main treatment period, 1 capsule in the morning and 1 capsule in the afternoon taken orally.
干预措施: Placebo (Drug)
Pridopidine
Pridopidine hard gelatin capsules of 45 mg strength. During titration period 1 capsule taken orally in the morning for 2 weeks. During the main treatment period, 1 capsule in the morning and 1 capsule in the afternoon taken orally. Total daily dose of 90 mg.
干预措施: Pridopidine (Drug)
结局指标
主要结局
Change from baseline through Week 26 and Week 48 in the Revised ALS Functional Rating Scale (ALSFRS-R) total score adjusted for mortality
时间窗: Baseline to Week 48
The ALSFRS-R encompasses 12 questions grouped into 4 domains to assess bulbar symptoms, limb and trunk functionality, respiratory symptoms, and the need for percutaneous endoscopic gastrostomy (PEG), non-invasive ventilation, or tracheostomy with invasive ventilation. Each function is scored from 0 (no ability) to 4 (normal), with a minimum total score of 0 and maximum total score of 48. Higher scores indicate better functioning.
Change from baseline through Week 26 and Week 48 in the Revised ALS Functional Rating Scale (ALSFRS-R) total score adjusted for mortality
时间窗: Baseline to Week 48
The ALSFRS-R encompasses 12 questions grouped into 4 domains to assess bulbar symptoms, limb and trunk functionality, respiratory symptoms, and the need for percutaneous endoscopic gastrostomy (PEG), non-invasive ventilation, or tracheostomy with invasive ventilation. Each function is scored from 0 (no ability) to 4 (normal), with a minimum total score of 0 and maximum total score of 48. Higher scores indicate better functioning.
次要结局
- Change from baseline through Week 26 and Week 48 in speaking rate as measured by quantitative speech assessment in the clinic(Baseline to Week 48)
- Overall survival at Week 96(Baseline to Week 96)
- Change from baseline through Week 48 in intelligibility of speech by quantitative speech assessment in the clinic.(Baseline to Week 48.)
- Change from baseline through Week 48 in percent predicted slow vital capacity (SVC)(Baseline to Week 48)
- Change from baseline through Week 48 in the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 40 (ALSAQ-40)(Baseline to Week 48)
- Change from baseline through Week 26 and Week 48 in speaking rate as measured by quantitative speech assessment in the clinic(Baseline to Week 48)
- Overall survival at Week 96(Baseline to Week 96)
- Change from baseline through Week 48 in intelligibility of speech by quantitative speech assessment in the clinic.(Baseline to Week 48.)
- Change from baseline through Week 48 in percent predicted slow vital capacity (SVC)(Baseline to Week 48)
- Change from baseline through Week 48 in the Bulbar subdomain of the ALSFRS-R(Baseline to Week 48)
- Change from baseline through Week 48 in the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 40 (ALSAQ-40)(Baseline to Week 48)