Huntington Disease
Conditions
Keywords
Huntington's Disease, SPK-10001, Adult-onset HD, HD, Rare Disease, Chorea, Movement Disorder, Spark Therapeutics, Cognition, Gene Therapy, AAV, mHTT
Brief summary
The main goal of this study is to evaluate the safety, tolerability, and preliminary efficacy of SPK-10001 in participants with Huntington's Disease.
Interventions
GENETICSPK-10001
Specified dose on specified days
OTHERPlacebo Surgery Control
Placebo Surgery procedure for SPK-10001
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
* Part A is open-label and non-randomized. * Part B is blinded and randomized. * Part C is open-label and non-randomized. * Part D is open-label and non-randomized.
Intervention model description
The study will be conducted in 4 sequential parts. * Part A is an open-label cohort in which all participants will receive SPK-10001. * Part B is randomized, double-blind and placebo-surgery-controlled. * Part C is a crossover open-label portion where participants who received placebo-surgery control in Part B will receive SPK-10001. * Part D is long term follow-up after completion of active treatment in any of Parts A, B, or C.
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have confirmed huntingtin (HTT) cytosine-adenine-guanine (CAG) repeat length ≥40 on genetic testing and confirmation diagnostic test by the central laboratory (CL) at screening. * Have striatal atrophy demonstrated by caudate/intracranial volume less than the age-adjusted cutoff values associated with HDISS Stage 1. * Have UHDRS Total Motor Score (TMS) equal to or greater than the age-adjusted cutoff value associated with HDISS Stage 2. * Have UHDRS Total Functional Capacity (TFC) greater than or equal to 11. * Use of cholinesterase inhibitors, memantine, amantadine, or riluzole must have been at stable dosing for at least 12 weeks before screening and baseline and anticipated to remain stable during the first 12 months after SPK-10001 administration. * Antidepressant or benzodiazepine use must have been at stable dosing for at least 12 weeks before screening and baseline and anticipated to remain stable during the first 12 months after SPK-10001 administration. * Antipsychotics for motor symptoms or mood stabilization (i.e., irritability or aggressive behavior) and/or tetrabenazine, valbenazine, or deutetrabenazine must have been at a stable dose for at least 12 weeks before screening and baseline and are anticipated to remain stable during the first 12 months after SPK-10001 administration. Key
Exclusion criteria
* A safe trajectory is not able to be identified for targeting placement of the cannula into the caudate or putamen on both sides of the brain due to extent of atrophy or other anatomical features. * Have received an antisense oligonucleotide therapy during the past year. * History of deep brain stimulation. * History of or intention to undergo gene therapy, cell transplantation, or brain surgery during the course of the study. * Have participated in an investigational drug study with a systemic administration within 6 weeks or 5 half-lives of screening, whichever is longer. Additional protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Day 1 up to approximately 5 years |
| Severity of TEAEs | Day 1 up to approximately 5 years |
| Change from Baseline in Unified Huntington's Disease Rating Scale (UHDRS®) Total Functional Capacity (TFC) Score | Baseline, Month 24 |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in Motor Symptom Progression Based on Huntington's Disease Digital Motor Score (HDDMS) | Baseline, Months 12, 18, and 24 |
| Change from Baseline in Composite UHDRS (cUHDRS) Score | Baseline, Months 12, 18, and 24 |
| Change from Baseline in UHDRS TFC Score | Baseline, Months 12 and 18 |
Countries
United States
Contacts
CONTACTReference Study ID Number: SPK-10001-101 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-LaRoche
Outcome results
None listed