Phase 2 N=159 Randomized Double-blind Treatment

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

Huntington Disease

Bottom Line

View on ClinicalTrials.gov: NCT05358717 ↗

Enrolled (actual)

159

Serious AEs

4.4%

Results posted

Jan 2026

Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 46; 43; 49 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: PTC518 (Drug); Placebo (Drug)
Age: Adult, Older Adult · 25+ yrs
Sex: All
Sponsor: PTC Therapeutics
Primary completion: Feb 2025

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs)	46; 43; 49	—
PRIMARY Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 3	-1.40; -17.36; -28.67	< 0.0001 sig
SECONDARY Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12	4.42; 4.99; 5.74	—
SECONDARY Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12	-0.64; -0.61; -0.92	—
SECONDARY Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 12	8.19; -14.18; -28.44	—
SECONDARY Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12	-15.64; -23.68; -23.28	—
SECONDARY Percent Change From Baseline in Blood mHTT Protein at Month 12	13.89; -14.11; -28.20	—

Summary

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

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05358717). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.