Huntington DiseasePhase 2NCT05358717
A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)
A Phase 2 study testing PTC518 in people with Huntington Disease, run by Novartis Pharmaceuticals at 28 sites in 11 countries.
Trial summary
The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Huntington Disease
- What is being tested?
- PTC518
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 159 participants
- Where
- 28 sitesin 11 countries
- Study dates
- 3 Jun 2022to 31 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
28 sites in 11 countries.
28 sites in 11 countries
United States4 sites
The University of Texas Health Science Center at Houston; McGovern Medical School
Houston, Texas, 77030
University of California, San Diego
La Jolla, California, 92037
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
University of Washington Department of Neurology
Seattle, Washington, 98195
Germany4 sites
Charite University Medicine Berlin
Berlin, 10117
Ruhr-Univ. Bochum St. Joseph-Hospital
Bochum, 44791
George-Huntington-Institut
Münster, 48149
Ulm University, UKU, Dep. of Neurology
Ulm, 89081
Spain4 sites
Hospital Universitario Cruces
Barakaldo, 48903
Hospital de la Santa Creu I Sant Pau
Barcelona, 8025
Hospital Universitario Burgos
Burgos, 90550
Hospital Ramón y Cajal
Madrid, 28034
United Kingdom4 sites
The Barbery National Centre for Mental Health
Birmingham, B15 2FG
Cardiff University Schools of Medicine and Biosciences
Cardiff, CF10 3AX
UCL Queen Square Institute of Neurology National Hospital for Neurology and Neurosurgery
London, WC1N 3BG
Manchester University NHS Foundation Trust
Manchester, M13 9WL
France3 sites
Centre Hospitalier Universitaire d'Angers
Angers, 49100
Hôpital Universitaire de Marseille Hôpital de la Timone
Marseille, 13385
Brain and Spine Institute Paris
Paris, 75013
Italy3 sites
Irccs Istituto Delle Scienze Neurologiche Di Bologna Uoc Clinica Neurologica
Bologna, 40139
IRCCS Carlo Besta Neurological Institutte
Milan, 20133
IRCCS Casa Sollievo della Sofferenza Research Hospital
San Giovanni Rotondo, 71013
Canada1 site
The Ottawa Hospital, Parkinson's and Movement Disorders Clinic
Ottawa, K1Y 4E9
New Zealand1 site
University of Otago, New Zealand Brain Research Institute
Christchurch, 8011
About this study
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
The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD.
Read the 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.
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).
- Conditions
- Huntington Disease
- Being tested
- PTC518, Placebo
- Keywords
- Neurodegenerative disorder, Rare disease
- Medical subject headings
- Huntington Disease, Neurodegenerative Diseases, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC518Drug
PTC518 will be administered per dose and schedule specified in the arm.
PlaceboDrug
Placebo matching to PTC518 will be administered per schedule specified in the arm.
| Study group | Role | What they receive |
|---|---|---|
| PTC518 5 mg | Experimental | Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months. Receives: Drug: PTC518 |
| PTC518 10 mg | Experimental | Participants will receive PTC518 10 mg tablets once daily orally for 12 months. Receives: Drug: PTC518 |
| PTC518 20 mg | Experimental | Participants will receive PTC518 20 mg tablets once daily orally for 12 months. Receives: Drug: PTC518 |
| Placebo | Placebo comparator | Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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'.
Measured: 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.
Measured: Baseline, Month 3
Secondary outcomes (5)
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.
Measured: Baseline, Month 12
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start3 Jun 2022
- Primary completion7 Feb 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05358717
- Sponsor's protocol ID
- PTC518-CNS-002-HD
- Other IDs
- 2021-003852-18
- Status last verified
- Dec 2025
- First submitted
- 27 Apr 2022
- Last updated
- 16 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38489195Estevez-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.
PubMed 36463457
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05358717
- Acronym / sponsor ID
- PTC518-CNS-002-HD
- Conditions
- Huntington Disease
- Keywords
- Neurodegenerative disorder, Rare disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Jun 2022 (actual)
- Primary completion
- 7 Feb 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 3 May 2022 (actual)
- Results
- Posted 13 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PTC518 5 mg | Experimental | Drug: PTC518Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months. |
| PTC518 10 mg | Experimental | Drug: PTC518Participants will receive PTC518 10 mg tablets once daily orally for 12 months. |
| PTC518 20 mg | Experimental | Drug: PTC518Participants will receive PTC518 20 mg tablets once daily orally for 12 months. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matching to PTC518 tablets once daily orally for 12 months. |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length from 40 to 50, inclusive
- 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)
- 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 (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTC518PTC518 will be administered per dose and schedule specified in the arm. | Drug | PTC518 10 mg, PTC518 20 mg, PTC518 5 mg |
| PlaceboPlacebo matching to PTC518 will be administered per schedule specified in the arm. | Drug | Placebo |
Primary outcome
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'.
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.
5 secondary outcomes
Percent Change From Baseline in Caudate Volume as Assessed Via Volumetric Magnetic Resonance Imaging (vMRI) at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Geometric Mean Blood tHTT Protein at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Blood mHTT Protein at Month 12
Time frame: Baseline, Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38489195Estevez-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.
- Derived from this study: PubMed 36463457Estevez-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.
Related trials for Huntington Disease
RecruitingPhase 2/3
Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease
Huntington Disease
RecruitingPhase 3
Pridopidine Phase 3 Study in Huntington's Disease
Huntington Disease
Not yet recruiting
Creatine and Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation Plus Home-Based Exercise for Sarcopenia in Huntington's Disease
Huntington Disease, Sarcopenia
Recruiting
Feasibility and Acceptability of an LLM-based Chatbot for Family Caregivers: Evaluation Study
Caregivers
RecruitingObservational study
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
28 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PTC518 in people with Huntington Disease, run by Novartis Pharmaceuticals at 28 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Germany, Spain, United Kingdom, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to Month 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05358717, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.