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

NCT05358717 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PTC518-CNS-002-HD2021-003852-18
• Study Type: interventional
• Target: 159
• Locations: 10 countries
• Sites: 27

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.

Conditions

Huntington Disease

Keywords

Neurodegenerative disorder; Rare disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as an AE that had an onset date or date of worsening on or after the first dose of study drug. A summary of other non-serious AEs and all serious adverse events (SAEs), regardless of causality is located in the 'Reported AE section'.

  Baseline up to Month 18

• Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 3

  Least square (LS) mean and 95% confidence interval (CI) were calculated using mixed-model repeated measures (MMRM). The blood tHTT protein value was log-transformed before fitting the MMRM model. The LS means from MMRM model were back-transformed to present geometric mean percent changes.

  Baseline, Month 3

Secondary Outcomes (5)

• Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) 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

• Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 12

  Baseline, Month 12

• Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12

  Baseline, Month 12

• Percent Change From Baseline in Blood mHTT Protein at Month 12

  Baseline, Month 12

Study Arms (4)

PTC518 5 mg

EXPERIMENTAL

Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months.

Drug: PTC518

PTC518 10 mg

EXPERIMENTAL

Participants will receive PTC518 10 mg tablets once daily orally for 12 months.

Drug: PTC518

PTC518 20 mg

EXPERIMENTAL

Participants will receive PTC518 20 mg tablets once daily orally for 12 months.

Drug: PTC518

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months.

Drug: Placebo

Interventions

PTC518 DRUG

PTC518 will be administered per dose and schedule specified in the arm.

PTC518 10 mg; PTC518 20 mg; PTC518 5 mg

Placebo DRUG

Placebo matching to PTC518 will be administered per schedule specified in the arm.

Placebo

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (28)

University of California, San Diego

La Jolla, California, 92037, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

The University of Texas Health Science Center at Houston; McGovern Medical School

Houston, Texas, 77030, United States

Location

University of Washington Department of Neurology

Seattle, Washington, 98195, United States

Location

Monash Health

Clayton, 3168, Australia

Location

Westmead Hospital

Sydney, 2145, Australia

Location

Medical University Innsbruck

Innsbruck, 6020, Austria

Location

The Ottawa Hospital, Parkinson's and Movement Disorders Clinic

Ottawa, K1Y 4E9, Canada

Location

Centre Hospitalier Universitaire d'Angers

Angers, 49100, France

Location

Hôpital Universitaire de Marseille Hôpital de la Timone

Marseille, 13385, France

Location

Brain and Spine Institute Paris

Paris, 75013, France

Location

Charite University Medicine Berlin

Berlin, 10117, Germany

Location

Ruhr-Univ. Bochum St. Joseph-Hospital

Bochum, 44791, Germany

Location

George-Huntington-Institut

Münster, 48149, Germany

Location

Ulm University, UKU, Dep. of Neurology

Ulm, 89081, Germany

Location

Irccs Istituto Delle Scienze Neurologiche Di Bologna Uoc Clinica Neurologica

Bologna, 40139, Italy

Location

IRCCS Carlo Besta Neurological Institutte

Milan, 20133, Italy

Location

IRCCS Casa Sollievo della Sofferenza Research Hospital

San Giovanni Rotondo, 71013, Italy

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

University of Otago, New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

Location

Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 8025, Spain

Location

Hospital Universitario Burgos

Burgos, 90550, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

The Barbery National Centre for Mental Health

Birmingham, B15 2FG, United Kingdom

Location

Cardiff University Schools of Medicine and Biosciences

Cardiff, CF10 3AX, United Kingdom

Location

UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Related Publications (2)

• Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.

  PMID: 38489195 DERIVED

• Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.

  PMID: 36463457 DERIVED

MeSH Terms

Conditions

Huntington Disease; Neurodegenerative Diseases; Rare Diseases

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: June 3, 2022
• Primary Completion: February 7, 2025
• Study Completion: July 31, 2025
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2025-12

Locations

DE (4); IT (3); NZ (1); FR (3); NL (1); GB (4); ES (4); US (4); AU (2); CA (1)