A Randomized, Placebo-controlled, Double-blind Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 770
- 试验地点
- 117
- 主要终点
- Change from Baseline in cUHDRS score
研究概览
简要总结
The purpose is to assess safety and tolerability of votoplam and to determine whether votoplam slows disease progression in patients with early symptomatic Huntington's disease (HD) compared to the control arm.
HTT227 - current compound code (former code is PTC518 from PTC Therapeutics), HTT227 is Novartis code under Novartis sponsorship.
详细描述
This study will have a variable double-blind treatment duration of up to 36 months. As part of the study design, not every participant will complete 36 months of treatment.
The study consists of 3 periods:
- Screening Period: A period of up to 42-days to assess participants eligibility
- Double-blind Treatment Period: This period will have variable individual treatment duration, up to 36 months. The double-blind treatment period concludes when ≥50% patients complete Month 36. The maximum treatment duration for an individual participant is 36 months.
- Safety Follow-up Period: A period consisting of one safety follow-up visit, conducted on site or by phone call, for all participants not continuing treatment in the separate open-label extension study or discontinuing early. The visit/phone call will take place 30 days after End of Study (EOS)
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
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consents must be obtained prior to participation in the study
- •Ambulatory male or female participants between 21 to 70 years of age, inclusive, on the day of Informed Consent signature
- •Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length of 40 or above. Participants must have prior genetic confirmation and known CAG repeat length obtained prior to screening.
- •Meets all of the following criteria:
- •UHDRS IS score ≥90
- •UHDRS TFC score = 13
- •UHDRS TMS score = 7-25, inclusive
- •CAP100 ≥ 70 Calculation: CAP = Age at study entry × (CAG length - 30) / 6.49
排除标准
- •History of gene therapy or cell transplantation or any other experimental brain surgery for the treatment of HD
- •Serologic evidence for active viral hepatitis as indicated by:
- •positive anti-HBc IgM
- •positive anti-HBc IgG confirmed by positive HBsAg and/or HBV DNA
- •positive HCV ab test confirmed by positive HCV RNA
- •Immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result
- •History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:
- •Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker
- •History of familial long QT syndrome or known family history of Torsade de Pointes
- •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In the case of oophorectomy alone, the reproductive status of the woman needs to have been confirmed by follow-up hormone level assessment.
- •o WOCBP are excluded unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 8 months after stopping study treatment.
- •Pregnant or nursing (breastfeeding) women
- •Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Votoplam
Votoplam (blinded) taken orally, randomized in a 3:2 ratio (Votoplam: Placebo)
干预措施: Votoplam (blinded) (Drug)
Placebo
Placebo (blinded) taken orally, randomized in a 3:2 ratio (Votoplam: Placebo)
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline in cUHDRS score
时间窗: Baseline, Month 36
The Composite Unified Huntingtons Disease Ratings Scale (cUHDRS) is an improved composite measure to assess multi-domain clinical progression in HD. The cUHDRS is a combined weighted score of measures of motor function (TMS), cognition (SDMT and SWRT) and overall functional capacity (TFC): cUHDRS = \[(TFC-10.4)/1.9 - (TMS-29.7)/14.9 + (SDMT-28.4)/11.3 + (SWRT - 66.1)/20.1\] + 10. In conjunction with one another, these measures provide a comprehensive, sensitive and specific tool for monitoring disease progression, with lower scores indicating more severe disease. cUHDRS score range from -8 to 25.
次要结局
- Change from Baseline in UHDRS-TFC(Baseline, Month 36)
- Change from Baseline in UHDRS-IS(Baseline, Month 36)
- The time to decline in TFC score by at least one or IS score by at least 10(Baseline to end of treatment up to 36 months)
- Change from Baseline in SWRT(Baseline, Month 36)
- Change from Baseline in UHDRS-TMS(Baseline, Month 36)
- Change from Baseline in SDMT(Baseline, Month 36)
- Change from Baseline in serum NfL(Baseline, Month 36)
- Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and TEAEs leading to participant withdrawal(Baseline to up to 36 months)
- Percent change from Baseline in blood mHTT protein(Baseline to steady state and up to 36 months in blood mHTT protein)