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

Huntington Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05358717
• Other study ID #: PTC518-CNS-002-HD
• Secondary ID: 2021-003852-18
• Status: Recruiting
• Phase: Phase 2
• Start date: April 25, 2022
• Est. completion date: July 31, 2024

Study information

• Verified date: March 2024
• Source: PTC Therapeutics
• Contact: Patient Advocacy
• Phone: 1-866-562-4620
• Email: medinfo[@]ptcbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 252
• Est. completion date: July 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Health	Clayton
Australia	Westmead Hospital	Sydney
Austria	Medical University Innsbruck	Innsbruck
Canada	Centre hospitalier de l'université de Montréal (CHUM)	Montreal
Canada	The Ottawa Hospital, Parkinson's and Movement Disorders Clinic	Ottawa
Canada	University of British Columbia (UBC)	Vancouver
France	Centre Hospitalier Universitaire d'Angers	Angers
France	Hôpital Universitaire de Marseille Hôpital de la Timone	Marseille
France	Brain and Spine Institute Paris	Paris
Germany	Ruhr-Univ. Bochum St. Joseph-Hospital	Bochum
Germany	George-Huntington-Institut	Münster
Germany	Ulm University, UKU, Dep. of Neurology	Ulm
Italy	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
Netherlands	Leiden University Medical Center	Leiden
New Zealand	University of Otago, New Zealand Brain Research Institute	Christchurch
Spain	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
United Kingdom	The Barbery National Centre for Mental Health	Birmingham
United Kingdom	Cardiff University Schools of Medicine and Biosciences	Cardiff
United Kingdom	The Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital	Leeds
United Kingdom	UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery	London
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	The University of Texas Health Science Center at Houston; McGovern Medical School	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University, G.H. Sergievsky Center	New York	New York
United States	University of Washington Department of Neurology	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Italy,  Netherlands,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)		Baseline up to Month 18
Primary	Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Month 3		Baseline, Month 3
Secondary	Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12		Baseline, Month 12
Secondary	Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12		Baseline, Month 12
Secondary	Change From Baseline in Blood tHTT Protein at Month 12		Baseline, Month 12
Secondary	Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12		Baseline, Month 12
Secondary	Change From Baseline in Blood mHTT Protein at Month 12		Baseline, Month 12