Clinical trial NCT05358717: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Huntington Disease
Keywords: Neurodegenerative disorder
Rare disease
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-05-03
Enrollment: 252
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Month 18
measure: Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Month 3
timeFrame: Baseline, Month 3
Secondary outcomes:
measure: Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Blood tHTT Protein at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Blood mHTT Protein at Month 12
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston; McGovern Medical School
state: Texas
city: Seattle
country: United States
facility: University of Washington Department of Neurology
state: Washington
city: Clayton
country: Australia
facility: Monash Health
city: Sydney
country: Australia
facility: Westmead Hospital
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Ottawa
country: Canada
facility: The Ottawa Hospital, Parkinson's and Movement Disorders Clinic
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Marseille
country: France
facility: Hôpital Universitaire de Marseille Hôpital de la Timone
city: Paris
country: France
facility: Brain and Spine Institute Paris
city: Berlin
country: Germany
facility: Charite University Medicine Berlin
city: Bochum
country: Germany
facility: Ruhr-Univ. Bochum St. Joseph-Hospital
city: Münster
country: Germany
facility: George-Huntington-Institut
city: Ulm
country: Germany
facility: Ulm University, UKU, Dep. of Neurology
city: Bologna
country: Italy
facility: Irccs Istituto Delle Scienze Neurologiche Di Bologna Uoc Clinica Neurologica
city: Milan
country: Italy
facility: IRCCS Carlo Besta Neurological Institutte
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza Research Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Christchurch
country: New Zealand
facility: University of Otago, New Zealand Brain Research Institute
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario Burgos
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Birmingham
country: United Kingdom
facility: The Barbery National Centre for Mental Health
city: Cardiff
country: United Kingdom
facility: Cardiff University Schools of Medicine and Biosciences
city: London
country: United Kingdom
facility: UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
References: