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

Last Update: Jul 29, 2026

A Randomized, Placebo-controlled, Double-blind Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

ClinicalTrials.gov Identifier:

NCT07326709

Novartis Reference Number:CHTT227A12301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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. 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)

Condition

Huntington Disease

Phase

Phase3

Overall Status

Recruiting

Number of Participants

770

Start Date

Mar 24, 2026

Completion Date

Apr 30, 2030

Gender

All

Age(s)

21 Years - 70 Years (Adult, Older Adult)

Interventions

Drug

Placebo

Drug

Votoplam (blinded)

Votoplam (blinded) active treatment

Eligibility 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

Novartis Investigative Site

Recruiting

CABA,Buenos Aires,C1056abi,Argentina

Novartis Investigative Site

Recruiting

CABA,Buenos Aires,1425,Argentina

Novartis Investigative Site

Recruiting

Caulfield South,Victoria,3162,Australia

CUSM Montreal Neurological Institute

Recruiting

Montreal,Quebec,H3a 2b4,Canada

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

Study Description

Interventions

Placebo

Votoplam (blinded)

Eligibility Criteria

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

CUSM Montreal Neurological Institute

Yara Nasr

Anne-Louise Lafontaine

Centre de recherche du CHUM

Alby Richard

Martine Comeau

North York General Hospital

Ragini Srinivasan, MD

Clare Gibbons

Novartis Investigative Site

West China Hospital of Sichuan Uni

Huifang Shang

Novartis Investigative Site

Novartis Investigative Site

Tel Aviv Sourasky Med Ctr Ichilov

Tanya Gurevich

Tanya Gurevich

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

University College Hospital

Sarah Tabrizi

Kate Fayer

Southampton General Hospital

Christopher Kipps

Giorgia Cortorillo

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

The University of Vermont MC

James Thomas Boyd

Nasim Nehzat

Georgetown University

Karen Anderson

Robin Kuprewicz

TX Movement Disorder Spec PLLC

Michael Soileau

Wendy White

University of Pennsylvania

Gwenivere Toti

Aaron Lasker

University of Washington Medical Center

Suman Jayadev

Debra Del Castillo

U of TX Health Science Ct

Erin Furr Stimming

Dane Weinig

Albany Medical College

Era Kaur Hanspal

Alicia Leader

Stanford Healthcare

Hengameh Zahed Kargaran

Jessica Yankulova

Henry Ford Health System

Bisena Bulica

Blagica Veselinova

University Of NC At Chapel Hill

Alexandra Seemungal

Claudia Testa

Uni Of Wisconsin Hosp And Clinic

Amy Nagel

Kathleen Shannon

UBMD Neurology

Sonia Joseph