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

PTC Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Huntington Disease

Treatments: Drug: Placebo; Drug: PTC518

Study type: Interventional

Funder types: Industry

Identifiers

NCT05358717

2021-003852-18 (EudraCT Number)

PTC518-CNS-002-HD

Details and patient eligibility

About

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

Full 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.

Enrollment: 252 estimated patients

Sex: All

Ages: 25+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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252 participants in 4 patient groups, including a placebo group

PTC518 5 mg

Experimental group

Description:

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

Treatment:

Drug: PTC518

PTC518 10 mg

Experimental group

Description:

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

Treatment:

Drug: PTC518

PTC518 20 mg

Experimental group

Description:

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

Treatment:

Drug: PTC518

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo