Overview
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.
Description
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)
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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
