A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05358717 |
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Recruitment Status :
Recruiting
First Posted : May 3, 2022
Last Update Posted : March 15, 2024
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Sponsor:
PTC Therapeutics
Information provided by (Responsible Party):
PTC Therapeutics
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Brief Summary:
The primary goal of this study is to evaluate the safety and pharmacodynamic effects of PTC518 compared with placebo in participants with HD.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Huntington Disease | Drug: PTC518 Drug: Placebo | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 252 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | April 25, 2022 |
| Estimated Primary Completion Date : | March 31, 2024 |
| Estimated Study Completion Date : | July 31, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Huntington disease
MedlinePlus related topics:
Huntington's Disease
| Arm | Intervention/treatment |
|---|---|
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Experimental: PTC518 5 mg
Participants will receive PTC518 5 milligrams (mg) tablets once daily orally for 12 months.
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Drug: PTC518
PTC518 will be administered per dose and schedule specified in the arm. |
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Experimental: PTC518 10 mg
Participants will receive PTC518 10 mg tablets once daily orally for 12 months.
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Drug: PTC518
PTC518 will be administered per dose and schedule specified in the arm. |
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Experimental: PTC518 20 mg
Participants will receive PTC518 20 mg tablets once daily orally for 12 months.
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Drug: PTC518
PTC518 will be administered per dose and schedule specified in the arm. |
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Placebo Comparator: Placebo
Participants will receive placebo matching to PTC518 tablets once daily orally for 12 months.
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Drug: Placebo
Placebo matching to PTC518 will be administered per schedule specified in the arm. |
Primary Outcome Measures :
- Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Month 18 ]
- Change From Baseline in Blood Total Huntingtin Protein (tHTT) at Month 3 [ Time Frame: Baseline, Month 3 ]
Secondary Outcome Measures :
- 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 ]
- Change From Baseline in Blood tHTT Protein at Month 12 [ Time Frame: Baseline, Month 12 ]
- Change From Baseline in Cerebrospinal Fluid (CSF) Mutant Huntingtin Protein (mHTT) at Month 12 [ Time Frame: Baseline, Month 12 ]
- Change From Baseline in Blood mHTT Protein at Month 12 [ Time Frame: Baseline, Month 12 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 25 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05358717
Contacts
| Contact: Patient Advocacy | 1-866-562-4620 | medinfo@ptcbio.com |
Locations
Show 34 study locations
Sponsors and Collaborators
PTC Therapeutics
| Responsible Party: | PTC Therapeutics |
| ClinicalTrials.gov Identifier: | NCT05358717 |
| Other Study ID Numbers: |
PTC518-CNS-002-HD 2021-003852-18 ( EudraCT Number ) |
| First Posted: | May 3, 2022 Key Record Dates |
| Last Update Posted: | March 15, 2024 |
| Last Verified: | March 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by PTC Therapeutics:
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Neurodegenerative disorder Rare disease |
Additional relevant MeSH terms:
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Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Dementia Chorea Dyskinesias |
Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Cognition Disorders Neurocognitive Disorders Mental Disorders |