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NCT Number: NCT05358717

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

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

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Key information

Conditions

Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Chorea Cognition Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dementia Disease Attributes Dyskinesias Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Mental Disorders Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Rare Diseases

Age range

25 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Monash Health, Clayton, Australia

Loading trial locations.

About this study

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.

Participants who complete this study and agree to participate in a long-term extension (LTE) study, will be enrolled in a separate LTE study PTC518-CNS-004-HD (NCT06254482).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PTC518

Drug

PTC518 will be administered per dose and schedule specified in the arm.

Placebo

Drug

Placebo matching to PTC518 will be administered per schedule specified in the arm.

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: Baseline up to Month 18

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as an AE that had an onset date or date of worsening on or after the first dose of study drug. A summary of other non-serious AEs and all serious adverse events (SAEs), regardless of causality is located in the 'Reported AE section'.

  2. Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 3

    Time frame: Baseline, Month 3

    Least square (LS) mean and 95% confidence interval (CI) were calculated using mixed-model repeated measures (MMRM). The blood tHTT protein value was log-transformed before fitting the MMRM model. The LS means from MMRM model were back-transformed to present geometric mean percent changes.

Secondary outcomes

  1. Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12

    Time frame: Baseline, Month 12

    LS mean and standard error (SE) were calculated using MMRM.

  2. Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12

    Time frame: Baseline, Month 12

    cUHDRS includes the Total Functional Capacity (range, 0-13; higher score means better functioning), Total Motor Score (range, 0-124; higher score means worse motor severity), Symbol Digit Modality Test (range, 0-110, correctly paired numbers-symbols in 90 seconds; higher score means better cognitive performance), and Stroop Word Reading (range, 0-no max value, correctly read colour words in 45 seconds; higher score means better cognitive performance) scores. The total score for the cUHDRS ranges from approximately 3 to 18, where higher scores indicated better functioning. LS mean and SE were calculated using analysis of covariance (ANCOVA) model.

  3. Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 12

    Time frame: Baseline, Month 12

    LS mean and 95% CI were calculated using MMRM. The blood tHTT protein value was log-transformed before fitting the MMRM model. The LS means from MMRM model were back-transformed to present geometric mean percent changes.

  4. Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12

    Time frame: Baseline, Month 12

    LS mean and 95% CI were calculated using MMRM. The CSF mHTT protein value was log-transformed before fitting the MMRM model. The LS means from MMRM model were back-transformed to present geometric mean percent changes.

  5. Percent Change From Baseline in Blood mHTT Protein at Month 12

    Time frame: Baseline, Month 12

    LS mean and 95% CI were calculated using MMRM. The blood mHTT protein value was log-transformed before fitting the MMRM model. The LS means from MMRM model were back-transformed to present geometric mean percent changes.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase 2A, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of PTC518 in Subjects With Huntington's Disease

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
May 3, 2022
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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