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
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 22
- 主要终点
- Changes in blood mHTT protein levels
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 clinical trial aims to evaluate the safety, pharmacodynamics, and efficacy of SKY-0515, a novel, orally-administered small molecule mRNA-splicing modulator for treating Huntington's Disease (HD). 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 by lowering of HTT messenger RNA (mRNA) through a splicing mechanism, 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. In early studies, SKY-0515 has reduced HTT and PMS1 mRNA levels in a dose-dependent manner, with favorable safety and tolerability profiles in healthy volunteers.
This study is a randomized, double-blind, placebo-controlled, trial conducted at multiple sites. 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) in a 1:1:1:1 ratio.
The study is composed of three periods:
- Screening Period (up to 4 weeks): Participants will undergo eligibility assessments.
- Double-Blind Treatment Period (12 months): Participants will take SKY-0515 or a placebo once daily and undergo regular clinic visits for monitoring. Safety and efficacy will be evaluated through blood tests, imaging (MRI), and clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS).
- Follow-Up Period (4 weeks): After completing treatment, participants will be monitored for any remaining effects.
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
- •You must be 25 years or older.
- •You must have Huntington's Disease confirmed through genetic testing, with a specific gene change (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.
- •You must agree to sign a consent form and follow the study's rules and schedule.
排除标准
- •You have other serious health problems or brain/spinal issues that could interfere with the study or make procedures unsafe.
- •You have a condition that interferes with protocol-specified assessments, like an implanted medical device or difficulty getting an MRI.
- •You have cancer, except for some types of skin cancer, or a history of cancer in the last five years.
- •You have severe allergies or have reacted badly to similar drugs in the past.
- •You are taking medications or treatments that might interfere with the study.
- •You've been in another study or taken experimental drugs in the last two months (or longer for some drugs).
- •You have had any kind of gene therapy.
- •You have a history of suicidal thoughts, severe depression, or have attempted suicide in the past year.
- •Your liver function tests show significant abnormalities.
- •You have tested positive for hepatitis B, hepatitis C, or HIV.
- •You are pregnant, breastfeeding, or planning to become pregnant during the study.
研究组 & 干预措施
1 (Active)
Dosage Level(s): Low dose once daily oral
干预措施: SKY-0515 (Drug)
2 (Active)
Dosage Level(s): Mid dose once daily oral
干预措施: SKY-0515 (Drug)
3 (Active)
Dosage Level(s): High dose once daily oral
干预措施: SKY-0515 (Drug)
4 (Control)
Matching placebo once daily oral
干预措施: SKY-0515 Placebo (Drug)
结局指标
主要结局
Changes in blood mHTT protein levels
时间窗: 12 months
Changes in brain volume measured through MRI
时间窗: 12 months
Changes in UHDRS
时间窗: 12 months
次要结局
未报告次要终点