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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-003852-18 | EudraCT Number |
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The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PTC518 5 mg | Experimental | Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months. |
|
| PTC518 10 mg | Experimental | Participants will receive PTC518 10 mg tablets once daily orally for 12 months. |
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| PTC518 20 mg | Experimental | Participants will receive PTC518 20 mg tablets once daily orally for 12 months. |
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| Placebo | Placebo Comparator | Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PTC518 | Drug | PTC518 will be administered per dose and schedule specified in the arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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'. | Baseline up to Month 18 |
| Percent Change From Baseline in Geometric Mean Blood tHTT Protein at 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. | Baseline, Month 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12 | LS mean and standard error (SE) were calculated using MMRM. | Baseline, Month 12 |
| Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12 |
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Key Inclusion Criteria:
Eligibility for HD-ISS Stage 2 Group (Parts A, B, and C):
Eligibility for HD-ISS Mild Stage 3 Group (Parts D, E, and F):
Key Exclusion Criteria:
Note: Other inclusion and exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego | La Jolla | California | 92037 | United States | ||
| Vanderbilt University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38489195 | Derived | Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017. | |
| 36463457 | Derived | Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006. |
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Participants were randomized to receive placebo, PTC518 5 milligrams (mg), or PTC518 10 mg. While the Independent Data Monitoring Committee authorized opening of the 20 mg dosing arm, the sponsor elected not to open PTC518 20 mg dosing arm for enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo matched to PTC518 tablets once daily (QD) orally for 12 months. |
| FG001 | PTC518 5 mg | Participants received 5 mg tablet of PTC518 QD orally for 12 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 5, 2023 | Dec 19, 2025 |
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| Placebo | Drug | Placebo matching to PTC518 will be administered per schedule specified in the arm. |
|
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. |
| Baseline, Month 12 |
| Percent Change From Baseline in Geometric Mean Blood tHTT Protein at 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. | Baseline, Month 12 |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at 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. | Baseline, Month 12 |
| Percent Change From Baseline in Blood mHTT Protein at 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. | Baseline, Month 12 |
| Nashville |
| Tennessee |
| 37212 |
| United States |
| The University of Texas Health Science Center at Houston; McGovern Medical School | Houston | Texas | 77030 | United States |
| University of Washington Department of Neurology | Seattle | Washington | 98195 | United States |
| Monash Health | Clayton | 3168 | Australia |
| Westmead Hospital | Sydney | 2145 | Australia |
| Medical University Innsbruck | Innsbruck | 6020 | Austria |
| The Ottawa Hospital, Parkinson's and Movement Disorders Clinic | Ottawa | K1Y 4E9 | Canada |
| Centre Hospitalier Universitaire d'Angers | Angers | 49100 | France |
| Hôpital Universitaire de Marseille Hôpital de la Timone | Marseille | 13385 | France |
| Brain and Spine Institute Paris | Paris | 75013 | France |
| Charite University Medicine Berlin | Berlin | 10117 | Germany |
| Ruhr-Univ. Bochum St. Joseph-Hospital | Bochum | 44791 | Germany |
| George-Huntington-Institut | Münster | 48149 | Germany |
| Ulm University, UKU, Dep. of Neurology | Ulm | 89081 | Germany |
| Irccs Istituto Delle Scienze Neurologiche Di Bologna Uoc Clinica Neurologica | Bologna | 40139 | Italy |
| IRCCS Carlo Besta Neurological Institutte | Milan | 20133 | Italy |
| IRCCS Casa Sollievo della Sofferenza Research Hospital | San Giovanni Rotondo | 71013 | Italy |
| Leiden University Medical Center | Leiden | 2333 ZA | Netherlands |
| University of Otago, New Zealand Brain Research Institute | Christchurch | 8011 | New Zealand |
| Hospital Universitario Cruces | Barakaldo | 48903 | Spain |
| Hospital de la Santa Creu I Sant Pau | Barcelona | 8025 | Spain |
| Hospital Universitario Burgos | Burgos | 90550 | Spain |
| Hospital Ramón y Cajal | Madrid | 28034 | Spain |
| The Barbery National Centre for Mental Health | Birmingham | B15 2FG | United Kingdom |
| Cardiff University Schools of Medicine and Biosciences | Cardiff | CF10 3AX | United Kingdom |
| UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery | London | WC1N 3BG | United Kingdom |
| Manchester University NHS Foundation Trust | Manchester | M13 9WL | United Kingdom |
| FG002 | PTC518 10 mg | Participants received 10 mg tablet of PTC518 QD orally for 12 months. |
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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Intent-to-treat (ITT) Population included all randomized participants who took at least 1 dose of the study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo matched to PTC518 tablets once daily (QD) orally for 12 months. |
| BG001 | PTC518 5 mg | Participants received 5 mg tablet of PTC518 QD orally for 12 months. |
| BG002 | PTC518 10 mg | Participants received 10 mg tablet of PTC518 QD orally for 12 months. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12 | LS mean and standard error (SE) were calculated using MMRM. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Least Squares Mean | Standard Error | percent change | Baseline, Month 12 |
|
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| |||||||||||||||||||||||||||||||
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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'. | Safety Population included all randomized participants who received at least 1 dose of the study drug, with participants grouped according to the treatment they received. | Posted | Count of Participants | Participants | Baseline up to Month 18 |
| ||||||||||||||||||||||||||||||||||
| Primary | Percent Change From Baseline in Geometric Mean Blood tHTT Protein at 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. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Geometric Mean | 95% Confidence Interval | percent change | Baseline, Month 3 |
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| Secondary | Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at 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. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Month 12 |
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| Secondary | Percent Change From Baseline in Geometric Mean Blood tHTT Protein at 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. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Geometric Mean | 95% Confidence Interval | percent change | Baseline, Month 12 |
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| Secondary | Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at 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. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Geometric Mean | 95% Confidence Interval | percent change | Baseline, Month 12 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in Blood mHTT Protein at 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. | ITT Population included all randomized participants who took at least 1 dose of the study drug. | Posted | Geometric Mean | 95% Confidence Interval | percent change | Baseline, Month 12 |
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Baseline up to Month 18
Safety Population included all randomized participants who received at least 1 dose of the study drug, with participants grouped according to the treatment they received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo matched to PTC518 tablets QD orally for 12 months. | 1 | 53 | 4 | 53 | 32 | 53 |
| EG001 | PTC518 5 mg | Participants received 5 mg tablet of PTC518 QD orally for 12 months. | 1 | 52 | 1 | 52 | 34 | 52 |
| EG002 | PTC518 10 mg | Participants received 10 mg tablet of PTC518 QD orally for 12 months. | 0 | 54 | 2 | 54 | 41 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bone marrow oedema | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Vestibular disorder | Ear and labyrinth disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Drowning | General disorders and administration site conditions | MedDRA 27.1 | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Fatigue | General disorders and administration site conditions | MedDRA 27.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA 27.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 27.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 27.1 | Systematic Assessment |
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The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patient Advocacy | PTC Therapeutics, Inc. | 1-866-562-4620 | medinfo@ptcbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 17, 2025 | Dec 19, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006816 | Huntington Disease |
| D019636 | Neurodegenerative Diseases |
| D035583 | Rare Diseases |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D002819 | Chorea |
| D020820 | Dyskinesias |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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