Votoplam for adults with early symptomatic Huntington's disease
A Randomized, Placebo-controlled, Double-blind Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease
This trial will test whether votoplam (HTT227) is safe and can slow disease progression in adults with early symptomatic Huntington's disease.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 770 (estimated) |
| Ages | 21 Years to 70 Years |
| Sex | All |
| Sponsor | Novartis Industry-sponsored |
| Locations | 10 sites (Englewood, Colorado and 9 other locations) |
| Trial ID | NCT07326709 on ClinicalTrials.gov |
What this trial studies
This Phase 3, randomized, double-blind, placebo-controlled trial tests votoplam (HTT227) in participants with early symptomatic Huntington's disease with a variable individual treatment duration of up to 36 months. After a screening period of up to 42 days, eligible participants meeting genetic and clinical criteria (including CAG repeat ≥40 and specified UHDRS and CAP100 scores) are randomized to blinded votoplam or placebo. The double-blind period concludes when at least 50% of participants reach month 36, and participants not entering an open-label extension have a single safety follow-up about 30 days after end of study. The main aims are to characterize safety and tolerability and to see if votoplam slows disease progression compared to placebo.
Who should consider this trial
Good fit: Ideal candidates are ambulatory adults aged 21–70 with genetically confirmed Huntington's disease (CAG ≥40) who meet the specified UHDRS and CAP100 eligibility criteria and can attend regular on-site visits.
Not a fit: Patients with advanced nonambulatory disease, prior experimental brain surgery or gene therapy, active viral hepatitis, or those who do not meet the trial's UHDRS/CAP criteria are unlikely to receive benefit from this study.
Why it matters
Potential benefit: If successful, votoplam could slow symptom progression in early Huntington's disease and offer a disease-modifying oral treatment option.
How similar studies have performed: HTT-lowering approaches (for example antisense oligonucleotides and other gene-silencing strategies) have shown mixed early results, and oral small-molecule HTT-lowering agents like HTT227 are relatively novel with limited late-stage evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
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. 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
Where this trial is running
Englewood, Colorado and 9 other locations
- CenExcel Rocky Mtn Clin Research — Englewood, Colorado, United States (Recruiting)
- Georgetown University — Washington D.C., District of Columbia, United States (Recruiting)
- Albany Medical College — Albany, New York, United States (Recruiting)
- UBMD Neurology — Buffalo, New York, United States (Recruiting)
- U of TX Health Science Ct — Houston, Texas, United States (Recruiting)
- University of Washington Medical Center — Seattle, Washington, United States (Recruiting)
- Novartis Investigative Site — North York, Ontario, Canada (Recruiting)
- Centre de recherche du CHUM — Montreal, Quebec, Canada (Recruiting)
- Novartis Investigative Site — Montreal, Quebec, Canada (Recruiting)
- Novartis Investigative Site — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Novartis Pharmaceuticals
- Email: novartis.email@novartis.com
- Phone: 1-888-669-6682
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.