A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

NCT07326709 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CHTT227A12301
• Study Type: interventional
• Target: 770
• Locations: 3 countries
• Sites: 10

Brief Summary

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.

Conditions

Huntington Disease

Keywords

HD; INVEST-HD; HTT227; VOTOPLAM; HUNTINGTON DISEASE; UHDRS; mHTT; NfL

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in cUHDRS score

  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.

  Baseline, Month 36

Secondary Outcomes (9)

• 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 UHDRS-TMS

  Baseline, Month 36

• Change from Baseline in SDMT

  Baseline, Month 36

Study Arms (2)

Votoplam

EXPERIMENTAL

Votoplam (blinded) taken orally, randomized in a 3:2 ratio (Votoplam: Placebo)

Drug: Votoplam (blinded)

Placebo

PLACEBO COMPARATOR

Placebo (blinded) taken orally, randomized in a 3:2 ratio (Votoplam: Placebo)

Drug: Placebo

Interventions

Votoplam (blinded) DRUG

Votoplam (blinded) active treatment

Also known as: HTT227

Votoplam

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

CenExcel Rocky Mtn Clin Research

Englewood, Colorado, 80113, United States

RECRUITING

Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Albany Medical College

Albany, New York, 12208, United States

RECRUITING

UBMD Neurology

Buffalo, New York, 14202, United States

RECRUITING

U of TX Health Science Ct

Houston, Texas, 77030, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Novartis Investigative Site

North York, Ontario, M2K1E1, Canada

RECRUITING

Centre de recherche du CHUM

Montreal, Quebec, H2W 1T8, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Novartis Investigative Site

London, NW1 2BU, United Kingdom

RECRUITING

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: January 8, 2026
• Study Start: March 24, 2026
• Primary Completion (Estimated): April 2, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); CA (3); US (6)