Votoplam (blinded): Votoplam (blinded) active treatment
Placebo: Placebo
Study 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.
Eligibility
Sex
ALL
Min age
21 Years
Max age
70 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Change from Baseline in cUHDRS score — Baseline, Month 36 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.
Trial sites (82)
Facility
City
Region
Status
University of Alabama Birmingham
Birmingham
Alabama
Recruiting
Univ of Arkansas for Med Sciences
Little Rock
Arkansas
Recruiting
University of CA San Diego
La Jolla
California
Recruiting
UC Davis Health System
Sacramento
California
Recruiting
Stanford Healthcare
Stanford
California
Recruiting
CenExcel Rocky Mtn Clin Research
Englewood
Colorado
Recruiting
U Conn Health
Farmington
Connecticut
Recruiting
Georgetown University
Washington D.C.
District of Columbia
Recruiting
University Of South Florida
Tampa
Florida
Recruiting
Grady Memorial Hospital and Clinics
Atlanta
Georgia
Recruiting
Parkinsons-Movement Disorder Ctr
Chicago
Illinois
Recruiting
Indiana University Health
Indianapolis
Indiana
Recruiting
University of Iowa Health Care
Iowa City
Iowa
Recruiting
University of Kansas Hospital
Fairway
Kansas
Recruiting
Beth Israel Deaconess Med Ctr
Boston
Massachusetts
Recruiting
Henry Ford Health System
Detroit
Michigan
Recruiting
Trinity Health Michigan
Grand Rapids
Michigan
Recruiting
Albany Medical College
Albany
New York
Recruiting
UBMD Neurology
Buffalo
New York
Recruiting
Columbia University Irving Medical
New York
New York
Recruiting
Universi of Rochester School of Med
Rochester
New York
Recruiting
University Of NC At Chapel Hill
Chapel Hill
North Carolina
Recruiting
Duke University Health System
Durham
North Carolina
Recruiting
Cleveland Clinic Foundation
Cleveland
Ohio
Recruiting
University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
University Of Pittsburgh
Pittsburgh
Pennsylvania
Recruiting
Veracity Neuroscience LLC
Memphis
Tennessee
Recruiting
Vanderbilt University Medical CenterX
Nashville
Tennessee
Recruiting
TX Movement Disorder Spec PLLC
Georgetown
Texas
Recruiting
U of TX Health Science Ct
Houston
Texas
Recruiting
The University of Vermont MC
Burlington
Vermont
Recruiting
VCU Health Systems MCV
Richmond
Virginia
Recruiting
University of Washington Medical Center
Seattle
Washington
Recruiting
Uni Of Wisconsin Hosp And Clinic
Madison
Wisconsin
Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Recruiting
Novartis Investigative Site
CABA
Buenos Aires
Recruiting
Novartis Investigative Site
Ciudad de
Buenos Aires
Recruiting
Novartis Investigative Site
Westmead
New South Wales
Recruiting
Novartis Investigative Site
Caulfield South
Victoria
Recruiting
Novartis Investigative Site
Leuven
Vlaams Brabant
Recruiting
+ 42 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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