An Extension Study to Evaluate the Long-Term Safety and Efficacy of Votoplam in Participants With Huntington's Disease (HD)

A Phase 2b, Double-Blind, Randomized Extension Study to Evaluate the Long-Term Safety and Efficacy of Votoplam in Participants With Huntington's Disease

The primary goal of this study is to evaluate the long-term safety and pharmacodynamic effects of votoplam in participants with HD.

Study Overview

• Status: Active, not recruiting
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Votoplam

Detailed Description

Participants who completed the Treatment Period in the parent Phase 2a Study PTC518-CNS-002-HD (NCT05358717), fulfilled the enrollment criteria, and chose to enroll in this extension study will undergo baseline evaluations and be assessed for 54 additional months.

All participants will receive active votoplam in this extension study. Participants who received votoplam in the parent Study PTC518-CNS-002-HD will continue at the same dose level they received in that study in a blinded fashion (5, 10 milligrams [mg]). Participants who received placebo in the parent Study PTC518-CNS-002-HD will be allocated to a votoplam dose level according to the same dosing group in which they were previously randomized (5, 10 mg).

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Novartis Investigative Site
  • Westmead, Australia, 2145
    • Novartis Investigative Site
• Austria
  • Innsbruck, Austria, 6020
    • Novartis Investigative Site
• Canada
  • Ottawa, Canada, K1Y 4E9
    • Novartis Investigative Site
• France
  • Angers, France, 49100
    • Novartis Investigative Site
  • Marseille, France, 13385
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Münster, Germany, 48149
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40139
    • Novartis Investigative Site
  • Milan, Italy, 20133
    • Novartis Investigative Site
  • San Giovanni Rotondo, Italy, 71013
    • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Novartis Investigative Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Novartis Investigative Site
• Spain
  • Barakaldo, Spain, 48903
    • Novartis Investigative Site
  • Barcelona, Spain, 8025
    • Novartis Investigative Site
  • Burgos, Spain, 90550
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2FG
    • Novartis Investigative Site
  • Cardiff, United Kingdom, CF14 4XW
    • Novartis Investigative Site
  • London, United Kingdom, WC1N 3BG
    • Novartis Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant who has completed the Treatment Period in Study PTC518-CNS-002-HD.

Exclusion Criteria:

• Participants who have not previously completed the Treatment Period in Study PTC518-CNS-002-HD.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Votoplam 5 mg; Participants will receive Votoplam 5 mg tablets once daily orally for 48 months.	Drug: Votoplam; Votoplam will be administered per dose and schedule specified in the arm.; Other Names: HTT227 / PTC518
Experimental: Votoplam 10 mg; Participants will receive votoplam 10 mg tablets once daily orally for 48 months.	Drug: Votoplam; Votoplam will be administered per dose and schedule specified in the arm.; Other Names: HTT227 / PTC518

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Baseline up to Month 54
Blood Total Huntingtin Protein (tHTT) Levels	Baseline up to Month 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 48	Baseline, Month 48
Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 48	Baseline, Month 48
Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) Levels	Baseline up to Month 48
Blood mHTT Protein Levels	Baseline up to Month 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Estimated): July 16, 2029
• Study Completion (Estimated): July 16, 2029

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Neurodegenerative disorder; Rare disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Rare Diseases; Neurodegenerative Diseases; Huntington Disease
• Other Study ID Numbers: PTC518-CNS-004-HD; 2023-504628-24-00 (Other Identifier: EU CT Number); CHTT227A12201 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No