A Phase 2A study of PTC518 in patients with Huntington's Disease

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 252

Inclusion Criteria

1. Ambulatory male or female patients aged 25 years and older, inclusive
2. Subject is willing and able to provide informed consent and comply with all protocol requirements
3. Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length from 42 to 50, inclusive. CAG repeat length may be determined analytically through amplification.

Eligibility for HD-ISS Stage 2 Group (Parts A, B, and C):
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)

Eligibility for HD-ISS Mild Stage 3 Group (Parts D, E, and F):
9. A UHDRS TFC score of 11 or 12, or a UHDRS TFC score of 13 with an
UHDRS IS score of
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 study drug and for 6 months after stopping 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 potential delivery of the drug via seminal fluid.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 216
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

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 including 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. Observational studies (such as ENROLL-HD) are not exclusionary
5. Presence of an implanted deep brain stimulation device
6. Family history of early onset cataracts or presence of significant cataracts at Baseline. Visually significant cataract is defined as any Lens Opacity Classification System II grading =2, Best Corrected Visual Acuity <20/40, cataract as the primary cause of vision impairment, and selfreported vision of fair or worse.
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 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 baseline version 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, antipsychotic 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. Benzodiazepine use for sedation for study-related procedures during the course of the study is permitted
15. History of illicit/illegal drug use, or alcohol use in the high-risk category of risk drinking levels according to the World Health Organization for a duration of 1 month or longer that in the opinion of the investigator could compromise the interpretability of study results
16. Clinically significant medical condition, which in the opinion of the investigator could adversely affect the safety of the subject or impair the assessment of study results (eg, inability to fast or any known hypersensitivity to PTC518 or its excipients)
17. Current significant renal impairment defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 at Screening
18. Current hepatic impairment resulting in elevated liver function tests (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP]) at 3 times the upper limit of normal at Screening
19. Pregnancy, plannin

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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