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NCT07326709PHASE3Recruiting

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

Novartis Pharmaceuticals

Start Date

3/24/2026

Completion Date

4/30/2030

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.

Detailed 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 Criteria

Age Range: 21 years to 70 years

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

Interventions

DRUG

Votoplam (blinded)

DRUG

Placebo

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Conditions

Huntington Disease

Locations

University of CA San Diego

La Jolla, California 92037

United States

Stanford Healthcare

Stanford, California 94305 5152

United States

CenExcel Rocky Mtn Clin Research

Englewood, Colorado 80113

United States

Georgetown University

Washington D.C., District of Columbia 20007

United States

University Of South Florida

Tampa, Florida 33612

United States

Parkinsons-Movement Disorder Ctr

Chicago, Illinois 60611

United States

Indiana University Health

Indianapolis, Indiana 46202

United States

University of Iowa Health Care

Iowa City, Iowa 52242-1091

United States

University of Kansas Hospital

Fairway, Kansas 66205

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Trinity Health Michigan

Grand Rapids, Michigan 49503

United States

Albany Medical College

Albany, New York 12208

United States

UBMD Neurology

Buffalo, New York 14202

United States

Columbia University Irving Medical

New York, New York 10032

United States

Universi of Rochester School of Med

Rochester, New York 14609

United States

University Of NC At Chapel Hill

Chapel Hill, North Carolina 27599 9500

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19107

United States

Veracity Neuroscience LLC

Memphis, Tennessee 38157

United States

Vanderbilt University Medical CenterX

Nashville, Tennessee 37221

United States

TX Movement Disorder Spec PLLC

Georgetown, Texas 78628

United States

U of TX Health Science Ct

Houston, Texas 77030

United States

The University of Vermont MC

Burlington, Vermont 05401

United States

University of Washington Medical Center

Seattle, Washington 98195

United States

Uni Of Wisconsin Hosp And Clinic

Madison, Wisconsin 53705-3611

United States

Novartis Investigative Site

CABA, Buenos Aires 1425

Argentina

Novartis Investigative Site

CABA, Buenos Aires C1056ABI

Argentina

Novartis Investigative Site

Caulfield South, Victoria 3162

Australia

North York General Hospital

North York, Ontario M2K1E1

Canada

Centre de recherche du CHUM

Montreal, Quebec H2W 1T8

Canada

CUSM Montreal Neurological Institute

Montreal, Quebec H3A 2B4

Canada

West China Hospital of Sichuan Uni

Chengdu, Sichuan 610041

China

Novartis Investigative Site

Hangzhou, Zhejiang 310002

China

Novartis Investigative Site

Bordeaux, 33076

France

Novartis Investigative Site

Montpellier, 34090

France

Tel Aviv Sourasky Med Ctr Ichilov

Tel Aviv, 6423906

Israel

Novartis Investigative Site

Dongjak Gu, Seoul 07061

South Korea

Novartis Investigative Site

Seoul, Seoul 03080

South Korea

Novartis Investigative Site

Busan, 47392

South Korea

Novartis Investigative Site

Basel, 4031

Switzerland

Novartis Investigative Site

Muri bei Bern, 3073

Switzerland

Novartis Investigative Site

Changhua, 50006

Taiwan

Novartis Investigative Site

Taipei, 11217

Taiwan

Novartis Investigative Site

Exeter, Devon EX2 5DW

United Kingdom

Novartis Investigative Site

Aberdeen, Grampian Region AB25 2ZN

United Kingdom

Novartis Investigative Site

Cambridge, CB2 0QQ

United Kingdom

Novartis Investigative Site

Cardiff, CF14 4XW

United Kingdom

Novartis Investigative Site

Glasgow, EH9 1LF

United Kingdom

University College Hospital

London, NW1 2BU

United Kingdom

Novartis Investigative Site

Oxford, OX3 9DU

United Kingdom

Southampton General Hospital

Southampton, SO16 6YD

United Kingdom