A Phase 2/3 Randomized, Double Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 33
- 主要终点
- Change From Baseline in the Z-score from the Composite Unified Huntington's Disease Rating Scale (cUHDRS)
研究概览
简要总结
The goal of this clinical trial is to test if the drug SKY-0515, an oral medication, can lower harmful proteins linked to Huntington's Disease (HD) and improve the symptoms of participants with HD. This study includes men and women aged 25 and older who have HD confirmed by genetic testing and meet certain requirements for physical ability and independence.
详细描述
This study is a randomized, double-blind, placebo-controlled trial conducted across multiple sites. This clinical trial aims to evaluate the safety, pharmacodynamics, and efficacy of SKY-0515, a novel, orally administered small molecule. Huntington's Disease (HD) is a rare, inherited neurodegenerative condition caused by a mutation in the huntingtin (HTT) gene, resulting in excessive production of mutant huntingtin (mHTT) protein, which damages nerve cells and leads to progressive motor, cognitive, and psychiatric symptoms. SKY-0515 is designed to reduce mHTT protein levels, leading to a decrease in both wild-type and mutant forms of HTT protein. Additionally, the drug lowers postmeiotic segregation 1 (PMS1) protein, which plays a role in somatic CAG repeat expansion-a key driver of HD progression. Participants must be aged 25 or older, have genetically confirmed HD (CAG repeat length ≥ 40), and meet specific functional and motor criteria. They will be assigned randomly to one of four treatment arms (three doses of SKY-0515 and one placebo group). Safety and efficacy will be evaluated through blood tests, imaging (MRI), and clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •25 years or older.
- •Huntington's Disease confirmed through genetic testing, with a specific change in exon 1 of the HTT gene (CAG repeat of 40 or more).
- •Total Functional Capacity (TFC) score of 10 or more).
- •Total Motor Score (TMS) of 6 or more).
- •Independence Score (IS) of 70 or more).
- •Women who can have children must have a negative pregnancy test before starting and use two types of birth control during the study and for 30 days after the last dose of the study drug.
- •Men must agree to use birth control during the study and for 90 days after the last dose.
- •Agree to sign a consent form and follow the study's rules and schedule.
排除标准
- •Other Serious health problems or brain/spinal issues that could interfere with the study or make procedures unsafe.
- •Conditions that interfere with protocol-specified assessments, like an implanted medical device or difficulty getting an MRI.
- •Cancer, except for some types of skin cancer, or a history of cancer in the last five years.
- •Severe allergies or have reacted badly to similar drugs in the past.
- •Taking medications or treatments that might interfere with the study.
- •Participated in another study or taken experimental drugs in the last two months (or longer for some drugs).
- •Any kind of gene therapy.
- •History of suicidal thoughts, severe depression, or have attempted suicide in the past year.
- •Liver function tests show significant abnormalities.
- •Positive for hepatitis B, hepatitis C, or HIV.
- •Pregnancy, breastfeeding, or planning to become pregnant during the study.
研究组 & 干预措施
Active Comparator (1)
Dosage Level(s): Low Dose
干预措施: SKY-0515 (Drug)
Active Comparator (3)
Dosage Level(s): High Dose
干预措施: SKY-0515 (Drug)
Active Comparator (2)
Dosage Level(s): Mid Dose
干预措施: SKY-0515 (Drug)
Placebo Comparator (4)
Matching placebo once daily oral
干预措施: SKY-0515 Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Z-score from the Composite Unified Huntington's Disease Rating Scale (cUHDRS)
时间窗: 72 weeks
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 Color and Word Test (range, 0-no max value, correctly read color 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.
次要结局
- Change from Baseline in Total Motor Score (TMS)(72 weeks)
- Change from Baseline in Total Functional Capacity (TFC)(72 weeks)
- Change from Baseline in Independence Scale Score (IS)(72 weeks)
- Change from Baseline in Symbol Digit Modalities Test (SDMT)(72 weeks)
- Change from Baseline in the Stroop Color and Word Test (SCWT)(72 weeks)