A study to evaluate the safety and efficacy of PTC518 in participants with Huntington's disease (HD)
- Conditions
- Huntington’s disease is an illness caused by a faulty gene in the DNA. Huntington’s affects the body’s nervous system – which can cause changes in movement, learning, thinking and emotions.Genetic DiseasesHuntington’s disease
- Registration Number
- ISRCTN97180769
- Lead Sponsor
- PTC Therapeutics International Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 252
Current inclusion criteria as of 25/07/2023:
Key Inclusion Criteria:
1. 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):
1. A Unified Huntington’s Disease Rating Scale (UHDRS)-Independence Scale (IS) score of 100
2. A UHDRS Total Functional Capacity (TFC) score of 13
3. 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):
1. 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
Note: Other inclusion criteria may apply.
Previous inclusion criteria:
1. Ambulatory male or female patients aged 25 years and older, inclusive
2. Subject (or legally authorized representative) is willing and able to provide informed consent and comply with all protocol requirements
3. Genetically confirmed HD diagnosis with a CAG repeat length from 42 to 50, inclusive
4. A UHDRS-IS score of 100
5. A UHDRS TFC score of 13
6. A score between 0.18 and 4.93 inclusive on the normed version of the HD prognostic index (PINHD)
7. Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception during dosing and for 6 months after stopping the study medication.
8. Sexually active and fertile males must agree to use a condom during intercourse while taking the study drug and for 6 months after stopping the study drug and should neither father a child nor donate sperm in this period. A condom is required to be used also by vasectomized men in order to prevent the potential delivery of the drug via seminal fluid.
Current exclusion criteria as of 25/07/2023:
Key Exclusion Criteria:
1. Receipt of an experimental agent within 90 days or 5 half-lives prior to Screening or anytime over the duration of this study, including ribonucleic acid (RNA)- or deoxyribonucleic acid (DNA)-targeted HD-specific investigational agents such as antisense oligonucleotides, cell transplantation, or any other experimental brain surgery
2. Any history of gene therapy exposure for the treatment of HD
3. 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
4. Any medical history of brain or spinal disease that would interfere with the lumbar puncture process safety assessments
5. 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)
6. Pregnancy, planning on becoming pregnant during the course of the study or within 6 months of the end of treatment, or currently breastfeeding
Note: Other exclusion criteria may apply.
Previous exclusion criteria:
1. Inability or unwillingness to swallow oral tablets
2. Receipt of an experimental agent within 90 days or 5 half-lives prior to Screening or anytime over the duration of this study, RNA- or DNA-targeted HD-specific investigational agents such as antisense oligonucleotides, cell transplantation, or any other experimental brain surgery
3. Any history of gene therapy exposure for the treatment of HD
4. 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
5. Presence of an implanted deep brain stimulation device
6. Family history of early onset cataracts or presence of cataracts at Baseline
7. Brain and spinal pathology that may interfere with CSF homeostasis and circulation, increased intracranial pressure (including presence of a shunt for the drainage of CSF or an implanted central nervous system catheter), malformations, and/or tumors
8. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
9. At significant risk of suicide as measured by the C-SSRS with a moderate risk rating or higher score
10. Risk of a major depressive episode, psychosis, confusional state, or violent behavior as assessed by the investigator
11. Any medical history of brain or spinal disease that would interfere with the lumbar puncture processor safety assessments
12. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
13. Any medical history or condition that would interfere with the ability to complete the protocol-specified assessments (eg, implanted shunt, conditions precluding MRI scans)
14. Antidepressant or benzodiazepine use, unless receiving a stable dose for at least 6 weeks prior to Screening and with a dose regimen that is not anticipated to change during the study
15. History of illicit/illegal drug use, or alcohol use in the high-risk category of risk drinking leve
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method