A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Clinical Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients With Manifest Huntington's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 899
- 试验地点
- 96
- 主要终点
- Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score
研究概览
简要总结
This study will evaluate the efficacy, safety, and biomarker effects of RO7234292 (RG6042) compared with placebo in participants with manifest Huntington's disease (HD)
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
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Manifest HD diagnosis, defined as a DCL score of 4
- •Independence Scale (IS) score >= 70
- •Genetically confirmed disease by direct DNA testing with a CAP score >400
- •Clinical assessment to ensure individual has intact functional independence at baseline to maintain self-care and core activities of daily living (ADLs).
排除标准
- •Any serious medical condition or clinically significant laboratory, or vital sign abnormality or claustrophobia at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug
研究组 & 干预措施
RO7234292 Q8W
RO4234292 is administered intrathecally every 8 weeks.
干预措施: RO7234292 (Drug)
RO7234292 Q16W
RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.
干预措施: RO7234292 (Drug)
RO7234292 Q16W
RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.
干预措施: Placebo (Drug)
Placebo
Placebo will be administered every 8 weeks by IT injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score
时间窗: Weeks 21 for ODC and 69 for NDC
cUHDRS includes the Total Functional Capacity (range, 0-13; higher score means better functioning), Total Motor Score (range, 0-124; higher score means worse motor severity), Symbol Digit Modality Test (range, 0-110, correctly paired numbers-symbols in 90 seconds; higher score means better cognitive performance), and Stroop Word Reading (range, 0-no max value, correctly read colour words in 45 seconds; higher score means better cognitive performance) scores. A z-score for each test is calculated, which alone can be used to describe relationship between an individual's test score and the mean score of a target population. A z-score of 0 is the mean, and ±1 is 1 standard deviation from the mean. For cUHDRS, z-scores of each test are summed, whereby a higher cUHDRS score is better (score of -3.06-no max value) and a change of ≥1.2 is a meaningful worsening, shown to track functional decline.
Change From Baseline in the Total Functional Capacity (TFC) Score
时间窗: Weeks 21 for ODC and 69 for NDC
Total Functional Capacity (TFC) Scores are reported at Weeks 21 and 69. Total Functional Capacity Score ranges from 0 to 13, with a higher score representing better functioning.
次要结局
- Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale Score(Weeks 53 and 69 NDC only)
- Trough Concentration of RO7234292 in Cerebrospinal Fluid (CSF)(Week 21 for ODC and Week 69 for NDC)
- Change From Baseline in Whole and Regional Brain Volumes, as Detrmined by Structural Magnetic Resonance Imaging (MRI)(Week 13 for ODC)
- Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level(Week 21 for ODC, Weeks 21 and 69 for NDC)
- Change From Baseline in Stroop Word Reading (SWR) Test Scores' Least Squares Mean Values(Weeks 21 for ODC and 69 for NDC)
- Percentage of Patients With a Decrease From Baseline of >=1 Point on the Total Functional Capacity (TFC) Score(Week 69 for NDC only)
- Change From Baseline in Total Motor Score (TMS)(Weeks 21 for ODC and 69 for NDC)
- Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores' Least Squares Mean Values(Weeks 21 for ODC and 69 NDC)
- Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) Scores' Least Squares Mean Values(Week 69 for NDC Only)
- Incidence of Anti-Drug Antibodies (ADAs).(Week 21 for ODC and Week 69 for NDC)
- Percentage of Patients With a Decline From Baseline of >=1.2 Points on the Composite Unified Huntington's Disease Rating Scale-cUHDRS Score(Week 69 for NDC Only)
- Percentage of Participants With Adverse Events(Up to 117 Weeks (29 months))
- Change From Baseline in Montreal Cognitive Assessment (MoCA)(Up to Week 21 for ODC, Up to Week 69 for NDC)
- Concentration of RO7234292 in Plasma(Week 21 for ODC and Week 69 for NDC)
- Change From Baseline in CSF mHTT Protein Level(Baseline, Week 101)
- Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score(For ODC at 13th Month, for NDC at Week 101)
- Titer and Antibody Subtype, Determined if ADAs Are Identified(Week 21 for ODC and Week 69 for NDC)