A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of Troriluzole in Adult Participants With Spinocerebellar Ataxia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 141
- 试验地点
- 18
- 主要终点
- Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
研究概览
简要总结
The primary purpose of this study was to compare the efficacy of BHV-4157 (Troriluzole) 140 milligrams (mg) once daily versus placebo after 8 weeks of treatment in participants with spinocerebellar ataxia (SCA).
详细描述
The study was conducted in 2 phases: Randomization Phase (8 weeks) followed by an open-label Extension Phase (336 weeks). During the Randomization Phase, participants received either Troriluzole 140 mg or matching placebo up to 8 weeks. Participants who agreed to enter the Open-label Extension Phase continued dosing of Troriluzole 140 mg for 336 weeks. The study was subsequently amended to follow participants for a total of 336 weeks in the Open-label Extension Phase.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10
- •Ability to ambulate 8 meters without assistance (canes and other devices allowed)
- •Screening total Scale for the Assessment and Rating of Ataxia (SARA) score ≥8
- •Score of ≥ 2 on the gait subsection of the SARA
- •Determined by the investigator to be medically stable at baseline/randomization and must be physically able and expected to complete the trial as designed
排除标准
- •Any medical condition other than one of the hereditary ataxias specified in the inclusion criteria that could predominantly explain or contribute significantly to the participants symptoms of ataxia
- •Mini Mental State Exam (MMSE) score < 24
- •SARA total score of > 30 points at screening
- •Clinical history of stroke
- •Active liver disease or a history of hepatic intolerance to medications that in the investigator's judgment, is medically significant
研究组 & 干预措施
Troriluzole - Randomization Phase
Troriluzole - Randomization Phase: Participants received Troriluzole 140 mg capsules orally once daily (QD) for 8 weeks.
干预措施: Troriluzole (Drug)
Placebo - Randomization Phase
Placebo - Randomization Phase: Participants received matching placebo capsules orally QD for 8 weeks.
干预措施: Placebo (Drug)
Troriluzole/Troriluzole - OLE (Open Label Extension) Phase
Participants received Troriluzole 140 mg capsules orally QD for 48 weeks in the extension period and were allowed to participate in 288 weeks for expanded extension phase, for a total of 336 weeks of open-label treatment.
干预措施: Troriluzole (Drug)
Placebo/Troriluzole - OLE Phase
Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks in the extension period and were allowed to participate in 288 weeks for expanded extension phase, for a total of 336 weeks of open-label treatment.
干预措施: Placebo (Drug)
Placebo/Troriluzole - OLE Phase
Participants who received placebo during randomization phase, received Troriluzole 140 mg capsules orally QD for 48 weeks in the extension period and were allowed to participate in 288 weeks for expanded extension phase, for a total of 336 weeks of open-label treatment.
干预措施: Troriluzole (Drug)
结局指标
主要结局
Change From Baseline in Total Score on the Scale for the Assessment and Rating of Ataxia (SARA) at Randomization Phase Week 8
时间窗: Baseline, Randomization Phase Week 8
The severity of ataxia was assessed with the SARA, an 8-item clinical rating scale from 0 (no ataxia) to 40 (most severe ataxia). The total score was derived as the sum of the individual items, which included gait (0-8), stance (0-6), sitting (0-4), speech disturbance (0-6), finger chase (0-4), nose-finger test (0-4), fast alternating hand movements (0-4), and heel-shin slide (0-4). Since the finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide were repeated on both the right and left side, the average of the right and left side assessments was used to derive the total score. A negative change in score shows improvement.
次要结局
- Number of Participants With Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Treatment-Emergent AEs (TEAEs) During the Randomization Phase(From first dose of study drug to 30 days post the last dose in the Randomization Phase (Up to 12 weeks))
- Number of Participants With Deaths, SAEs, AEs Leading to Discontinuation and TEAEs During the OLE Phase(From first dose of study drug to 30 days post the last dose in the OLE Phase (Up to 340 weeks))
- Number of Participants Who Received At Least One Dose of Troriluzole in the Randomization Phase or OLE Phase With Deaths, SAEs, AEs Leading to Discontinuation and TEAEs(From first dose of study drug to 30 days post the last dose in the OLE Phase (Up to 348 weeks after last randomization participant was enrolled))
- Number of Participants With Impression of Benefit Via Use of the Patient Global Impression of Change (PGI-C) Index Scale During Randomization Phase(Randomization Phase Week 8)