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: 27 countries
• Sites: 117

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

Placebo DRUG

Placebo

Placebo

Votoplam (blinded) DRUG

Votoplam (blinded) active treatment

Also known as: HTT227

Votoplam

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 (117)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Univ of Arkansas for Med Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

University of CA San Diego

La Jolla, California, 92037, United States

RECRUITING

UC Davis Health System

Sacramento, California, 95817, United States

RECRUITING

UCSF

San Francisco, California, 94115, United States

RECRUITING

Stanford Healthcare

Stanford, California, 94305-5152, United States

RECRUITING

CenExcel Rocky Mtn Clin Research

Englewood, Colorado, 80113, United States

RECRUITING

U Conn Health

Farmington, Connecticut, 06030, United States

RECRUITING

Georgetown University

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

RECRUITING

UM Department Of Neurology

Miami, Florida, 33136, United States

RECRUITING

University Of South Florida

Tampa, Florida, 33612, United States

RECRUITING

Grady Memorial Hospital and Clinics

Atlanta, Georgia, 30303, United States

RECRUITING

Parkinsons-Movement Disorder Ctr

Chicago, Illinois, 60611, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Indiana University Health

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Health Care

Iowa City, Iowa, 52242-1091, United States

RECRUITING

University of Kansas Hospital

Fairway, Kansas, 66205, United States

RECRUITING

Hereditary Neurological Disease Centre

Wichita, Kansas, 67226, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Trinity Health Michigan

Grand Rapids, Michigan, 49503, United States

RECRUITING

Albany Medical College

Albany, New York, 12208, United States

RECRUITING

UBMD Neurology

Buffalo, New York, 14202, United States

RECRUITING

Columbia University Irving Medical

New York, New York, 10032, United States

RECRUITING

Universi of Rochester School of Med

Rochester, New York, 14609, United States

RECRUITING

University Of NC At Chapel Hill

Chapel Hill, North Carolina, 27599-9500, United States

RECRUITING

Duke University Health System

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health Sciences University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University Of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Veracity Neuroscience LLC

Memphis, Tennessee, 38157, United States

RECRUITING

Vanderbilt University Medical CenterX

Nashville, Tennessee, 37221, United States

RECRUITING

TX Movement Disorder Spec PLLC

Georgetown, Texas, 78628, United States

RECRUITING

U of TX Health Science Ct

Houston, Texas, 77030, United States

RECRUITING

The University of Vermont MC

Burlington, Vermont, 05401, United States

RECRUITING

VCU Health Systems MCV

Richmond, Virginia, 23298, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Uni Of Wisconsin Hosp And Clinic

Madison, Wisconsin, 53705-3611, United States

RECRUITING

Instituto Argentino de Investigación Neurológica (IADIN)

CABA, Buenos Aires, 1425, Argentina

RECRUITING

Centro de Investigaciones Metabólicas (CINME)

CABA, Buenos Aires, C1056ABI, Argentina

RECRUITING

Novartis Investigative Site

Ciudad de, Buenos Aires, C1425DND, Argentina

RECRUITING

Novartis Investigative Site

Buenos Aires, 1060, Argentina

RECRUITING

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

RECRUITING

Novartis Investigative Site

Caulfield South, Victoria, 3162, Australia

RECRUITING

Novartis Investigative Site

Leuven, Vlaams Brabant, 3000, Belgium

RECRUITING

Novartis Investigative Site

Sofia, 1113, Bulgaria

RECRUITING

Novartis Investigative Site

Sofia, 1431, Bulgaria

RECRUITING

North York General Hospital

North York, Ontario, M2K1E1, Canada

RECRUITING

Centre de recherche du CHUM

Montreal, Quebec, H2W 1T8, Canada

RECRUITING

CUSM Montreal Neurological Institute

Montreal, Quebec, H3A 2B4, Canada

RECRUITING

Novartis Investigative Site

Fuzhou, Fujian, 350000, China

RECRUITING

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

RECRUITING

Novartis Investigative Site

Guangzhou, Guangdong, 510120, China

RECRUITING

Tongji Hos Affiliated Tongji Medical College of Huazhong

Wuhan, Hubei, 430030, China

RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

RECRUITING

West China Hospital of Sichuan Uni

Chengdu, Sichuan, 610041, China

RECRUITING

The Second Affiliated Hosp Of Zhejiang Univ School Of Medicine

Hangzhou, Zhejiang, 310002, China

RECRUITING

Novartis Investigative Site

Beijing, 100053, China

RECRUITING

Novartis Investigative Site

Beijing, 100070, China

RECRUITING

Novartis Investigative Site

Shanghai, 200233, China

RECRUITING

Novartis Investigative Site

Medellín, 050001, Colombia

RECRUITING

Novartis Investigative Site

Brno, 602 00, Czechia

RECRUITING

Novartis Investigative Site

Prague, 128 08, Czechia

RECRUITING

Novartis Investigative Site

Copenhagen, 2100, Denmark

RECRUITING

Novartis Investigative Site

Angers, France, 49933, France

RECRUITING

Novartis Investigative Site

Marseille, 13885, France

RECRUITING

Novartis Investigative Site

Montpellier, 34090, France

RECRUITING

Novartis Investigative Site

Aachen, 52074, Germany

RECRUITING

Novartis Investigative Site

Bochum, 44791, Germany

RECRUITING

Novartis Investigative Site

Münster, 48149, Germany

RECRUITING

Novartis Investigative Site

Tübingen, 72076, Germany

RECRUITING

Novartis Investigative Site

Ulm, 89081, Germany

RECRUITING

Novartis Investigative Site

Budapest, 1083, Hungary

RECRUITING

Novartis Investigative Site

Szeged, 6725, Hungary

RECRUITING

Tel Aviv Sourasky Med Ctr Ichilov

Tel Aviv, 6423906, Israel

RECRUITING

Novartis Investigative Site

Bologna, BO, 40139, Italy

RECRUITING

Novartis Investigative Site

Brescia, BS, 25123, Italy

RECRUITING

Novartis Investigative Site

Milan, MI, 20133, Italy

RECRUITING

Novartis Investigative Site

Milan, MI, 20149, Italy

RECRUITING

Novartis Investigative Site

Sagamihara, Kanagawa, 2520392, Japan

RECRUITING

Novartis Investigative Site

Kashihara, Nara, 6348522, Japan

RECRUITING

Novartis Investigative Site

Bunkyo Ku, Tokyo, 1138655, Japan

RECRUITING

Novartis Investigative Site

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Novartis Investigative Site

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Novartis Investigative Site

Krakow, POL, 31-505, Poland

RECRUITING

Novartis Investigative Site

Lisbon, 1649-035, Portugal

RECRUITING

Novartis Investigative Site

Porto, 4099-001, Portugal

RECRUITING

Novartis Investigative Site

Bucharest, 040215, Romania

RECRUITING

Novartis Investigative Site

Târgu Mureş, 540136, Romania

RECRUITING

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

RECRUITING

Novartis Investigative Site

Košice, 041 90, Slovakia

RECRUITING

Novartis Investigative Site

Daejeon, Korea, 35015, South Korea

RECRUITING

SMG SNU Boramae Medical Center

Dongjak Gu, Seoul, 07061, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul, 03080, South Korea

RECRUITING

Inje University Busan Paik Hospital

Busan, 47392, South Korea

RECRUITING

Novartis Investigative Site

Palma, Balearic Islands, 07120, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08035, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08041, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28034, Spain

RECRUITING

Novartis Investigative Site

Seville, 41009, Spain

RECRUITING

Novartis Investigative Site

Basel, 4031, Switzerland

RECRUITING

Novartis Investigative Site

Muri bei Bern, 3073, Switzerland

RECRUITING

Novartis Investigative Site

Changhua, 50006, Taiwan

RECRUITING

Novartis Investigative Site

Taipei, 11217, Taiwan

RECRUITING

Novartis Investigative Site

Taoyuan, 33305, Taiwan

RECRUITING

Novartis Investigative Site

Exeter, Devon, EX2 5DW, United Kingdom

RECRUITING

Novartis Investigative Site

Aberdeen, Grampian Region, AB25 2ZN, United Kingdom

RECRUITING

Novartis Investigative Site

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Novartis Investigative Site

Cardiff, CF14 4XW, United Kingdom

RECRUITING

Novartis Investigative Site

Glasgow, EH9 1LF, United Kingdom

RECRUITING

Novartis Investigative Site

Leeds, LS1 3EX, United Kingdom

RECRUITING

University College Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Novartis Investigative Site

London, SW17 0QT, United Kingdom

RECRUITING

Novartis Investigative Site

Oxford, OX3 9DU, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, 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: September 22, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

SA (1); CZ (2); HU (2); BU (2); RO (2); SL (1); NL (2); DE (5); FR (3); AU (2); GB (10); CN (10); CA (3); US (40); KR (4); TW (3); IL (1); CH (2); AR (4); ES (5); BE (1); JP (3); DK (1); PL (1); PT (2); CO (1); IT (4)