Last Update: Jun 23, 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:
Novartis Reference Number:CHTT227A12301
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)

Huntington Disease
Phase3
Recruiting
770
Mar 24, 2026
Apr 30, 2030
All
21 Years - 70 Years (Adult, Older Adult)

Interventions

Drug

Placebo

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

CUSM Montreal Neurological Institute

Recruiting

Montreal,Quebec,H3a 2b4,Canada

Anne-Louise Lafontaine
Yara Nasr

North York General Hospital

Recruiting

North York,Ontario,M2k1e1,Canada

Ragini Srinivasan, MD
Clare Gibbons

Centre de recherche du CHUM

Recruiting

Montreal,Quebec,H2w 1t8,Canada

Alby Richard
Martine Comeau

Novartis Investigative Site

Recruiting

Chengdu,Sichuan,610041,China

Tel Aviv Sourasky Med Ctr Ichilov

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Tel Aviv,6423906,Israel

Tanya Gurevich
Tanya Gurevich

Novartis Investigative Site

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Seoul,Seoul,03080,South Korea

Novartis Investigative Site

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Taipei,11217,Taiwan

University College Hospital

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London,Nw1 2bu,United Kingdom

Sarah Tabrizi
Kate Fayer

Southampton General Hospital

Recruiting

Southampton,So16 6yd,United Kingdom

Christopher Kipps
Giorgia Cortorillo

Novartis Investigative Site

Recruiting

Aberdeen,Grampian Region,Ab25 2zn,United Kingdom

Novartis Investigative Site

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Cardiff,Cf14 4xw,United Kingdom

Novartis Investigative Site

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Glasgow,G51 4tf,United Kingdom

Novartis Investigative Site

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Exeter,Devon,Ex2 5dw,United Kingdom

Parkinsons-Movement Disorder Ctr

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Chicago,Illinois,60611,United States

Zsa Zsa Brown
Danny Bega

University of Kansas Hospital

Recruiting

Fairway,Kansas,66205,United States

Cameron Zoraghchi
Richard Dubinsky

Columbia University Irving Medical

Recruiting

New York,New York,10032,United States

Karen Marder
Sandra Rizer

Veracity Neuroscience LLC

Recruiting

Memphis,Tennessee,38157,United States

Jennifer Marshall
Mark Steven LeDoux

University of CA San Diego

Recruiting

La Jolla,California,92037,United States

Jody Corey-Bloom
Krisha Bagga

Cleveland Clinic Foundation

Recruiting

Cleveland,Ohio,44195,United States

Margaret Andorf
Adam Margolius

U of TX Health Science Ct

Recruiting

Houston,Texas,77030,United States

Erin Furr Stimming
Dane Weinig

Georgetown University

Recruiting

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

Robin Kuprewicz
Karen Anderson

CenExcel Rocky Mtn Clin Research

Recruiting

Englewood,Colorado,80113,United States

Liza Heap
Meagen Salinas

UBMD Neurology

Recruiting

Buffalo,New York,14202,United States

Kelly Andrzejewski
Sonia Joseph

Albany Medical College

Recruiting

Albany,New York,12208,United States

Alicia Leader
Era Kaur Hanspal

University of Washington Medical Center

Recruiting

Seattle,Washington,98195,United States

Debra Del Castillo
Suman Jayadev

University of Pennsylvania

Recruiting

Philadelphia,Pennsylvania,19107,United States

Aaron Lasker
Gwenivere Toti

TX Movement Disorder Spec PLLC

Recruiting

Georgetown,Texas,78628,United States

Michael Soileau
Wendy White

Worldwide Contacts

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Novartis Pharmaceuticals

Novartis Pharmaceuticals