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

• ClinicalTrials.gov Identifier: NCT05358717
• Recruitment Status: Recruiting
• First Posted: May 3, 2022
• Last Update Posted: March 15, 2024
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Tracking Information

• First Submitted Date: April 27, 2022
• First Posted Date: May 3, 2022
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: April 25, 2022
• Estimated Primary Completion Date: March 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2023)

• Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Month 18 ]
• Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Month 3 [ Time Frame: Baseline, Month 3 ]

Original Primary Outcome Measures (submitted: April 27, 2022)

• Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Day 113 ]
• Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Day 85 [ Time Frame: Baseline, Day 85 ]

Current Secondary Outcome Measures (submitted: July 14, 2023)

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

Original Secondary Outcome Measures (submitted: April 27, 2022)

• Change From Baseline in Blood HTT Messenger Ribonucleic Acid (mRNA) at Days 29, 57, and 85 [ Time Frame: Baseline, Days 29, 57, and 85 ]
• Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Day 85 [ Time Frame: Baseline, Day 85 ]
• Change From Baseline in Blood mHTT at Day 85 [ Time Frame: Baseline, Day 85 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)
• Official Title: A Phase 2A, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of PTC518 in Subjects With Huntington's Disease
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Huntington Disease

Intervention

• Drug: PTC518
  PTC518 will be administered per dose and schedule specified in the arm.
• Drug: Placebo
  Placebo matching to PTC518 will be administered per schedule specified in the arm.

Study Arms

• Experimental: PTC518 5 mg
  Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months.
  Intervention: Drug: PTC518
• Experimental: PTC518 10 mg
  Participants will receive PTC518 10 mg tablets once daily orally for 12 months.
  Intervention: Drug: PTC518
• Experimental: PTC518 20 mg
  Participants will receive PTC518 20 mg tablets once daily orally for 12 months.
  Intervention: Drug: PTC518
• Placebo Comparator: Placebo
  Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 14, 2023): 252
• Original Estimated Enrollment (submitted: April 27, 2022): 162
• Estimated Study Completion Date: July 31, 2024
• Estimated Primary Completion Date: March 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Patient Advocacy; 1-866-562-4620; medinfo@ptcbio.com

• Listed Location Countries: Australia, Austria, Canada, France, Germany, Italy, Netherlands, New Zealand, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05358717
• Other Study ID Numbers: PTC518-CNS-002-HD; 2021-003852-18 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: PTC Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: PTC Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PTC Therapeutics
• Verification Date: March 2024