A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)

Phase 2

Active, not recruiting

• Conditions: Huntington Disease
• Interventions: Drug: PTC518; Drug: Placebo

• Registration Number: NCT05358717
• Lead Sponsor: PTC Therapeutics

Brief Summary

The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD.

Detailed Description

Participants will first be randomized to Part A or Part B or Parts D or E in a 1:1 randomization ratio, depending on their Huntington's disease Integrated Staging System (HD-ISS) staging criteria and then to active treatment (PTC518 5 mg in Parts A and D and 10 mg in Parts B and E) or matching placebo within each part in a 2:1 ratio of active treatment to placebo. A Drug Safety Monitoring Board (DSMB) Charter will undertake an unblinded review of safety data from the 5 and 10 mg dosing groups and provide a recommendation on when Parts C and F (with a 20 mg active treatment arm) can be initiated. At that time, participants will be randomized to any study Part that is currently open for enrollment, and then to either active treatment or placebo (in a 2:1 ratio) within that Part.

Study Timeline

• Study Start: 2022-04-25
• Study First Submitted: 2022-04-27
• Study First Submitted QC: 2022-04-27
• Study First Posted: 2022-05-03
• Status Verified: 2025-02
• Primary Completion: 2025-02-15
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-20
• Study Completion: 2025-08-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

• Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length from 40 to 50, inclusive

Eligibility for HD-ISS Stage 2 Group (Parts A, B, and C):

• A Unified Huntington's Disease Rating Scale (UHDRS)-Independence Scale (IS) score of 100
• A UHDRS Total Functional Capacity (TFC) score of 13
• A score between 0.18 and 4.93 inclusive on the normed version of the HD prognostic index (PINHD)

Eligibility for HD-ISS Mild Stage 3 Group (Parts D, E, and F):

• A UHDRS Total Functional Capacity (TFC) score of 11 or 12, or a UHDRS TFC score of 13 with an UHDRS IS score of <100

Key

Exclusion Criteria

• Receipt of an experimental agent within 90 days or 5 half-lives prior to Screening or anytime over the duration of this study, ribonucleic acid (RNA)- or deoxyribonucleic acid (DNA)-targeted HD-specific investigational agents such as antisense oligonucleotides, cell transplantation, or any other experimental brain surgery
• Any history of gene therapy exposure for the treatment of HD
• Participation in an investigational study or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation, etc) within 90 days prior to Screening or anytime over the duration of this study
• Any medical history of brain or spinal disease that would interfere with the lumbar puncture process safety assessments
• Any medical history or condition that would interfere with the ability to complete the protocol-specified assessments (for example, implanted shunt, conditions precluding magnetic resonance imaging [MRI] scans)
• Pregnancy, planning on becoming pregnant during the course of the study or within 6 months of end of treatment, or currently breastfeeding

Note: Other inclusion and exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PTC518 20 mg	PTC518	Participants will receive PTC518 20 mg tablets once daily orally for 12 months.
Placebo	Placebo	Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months.
PTC518 5 mg	PTC518	Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months.
PTC518 10 mg	PTC518	Participants will receive PTC518 10 mg tablets once daily orally for 12 months.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Month 3	Baseline, Month 3
Number of Participants With Adverse Events (AEs)	Baseline up to Month 18

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12	Baseline, Month 12
Change From Baseline in Blood tHTT Protein at Month 12	Baseline, Month 12
Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12	Baseline, Month 12
Change From Baseline in Blood mHTT Protein at Month 12	Baseline, Month 12
Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12	Baseline, Month 12

Trial Locations

Locations (28)

Charite University Medicine Berlin; 🇩🇪 Berlin, Germany

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

The University of Texas Health Science Center at Houston; McGovern Medical School; 🇺🇸 Houston, Texas, United States

University of Washington Department of Neurology; 🇺🇸 Seattle, Washington, United States

Monash Health; 🇦🇺 Clayton, Australia

Westmead Hospital; 🇦🇺 Sydney, Australia

Medical University Innsbruck; 🇦🇹 Innsbruck, Austria

The Ottawa Hospital, Parkinson's and Movement Disorders Clinic; 🇨🇦 Ottawa, Canada

Centre Hospitalier Universitaire d'Angers; 🇫🇷 Angers, France

Hôpital Universitaire de Marseille Hôpital de la Timone; 🇫🇷 Marseille, France

Brain and Spine Institute Paris; 🇫🇷 Paris, France

Ruhr-Univ. Bochum St. Joseph-Hospital; 🇩🇪 Bochum, Germany

George-Huntington-Institut; 🇩🇪 Münster, Germany

Ulm University, UKU, Dep. of Neurology; 🇩🇪 Ulm, Germany

Irccs Istituto Delle Scienze Neurologiche Di Bologna Uoc Clinica Neurologica; 🇮🇹 Bologna, Italy

IRCCS Carlo Besta Neurological Institutte; 🇮🇹 Milan, Italy

IRCCS Casa Sollievo della Sofferenza Research Hospital; 🇮🇹 San Giovanni Rotondo, Italy

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

University of Otago, New Zealand Brain Research Institute; 🇳🇿 Christchurch, New Zealand

Hospital Universitario Cruces; 🇪🇸 Barakaldo, Spain

Hospital de la Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario Burgos; 🇪🇸 Burgos, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

The Barbery National Centre for Mental Health; 🇬🇧 Birmingham, United Kingdom

Cardiff University Schools of Medicine and Biosciences; 🇬🇧 Cardiff, United Kingdom

UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery; 🇬🇧 London, United Kingdom

Manchester University NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom