Clinical trial NCT06826612: A Randomized Study of SPK-10001 Gene Therapy in Participants With Huntington's Disease
Official title: A Phase 1/2, Randomized, Sequential, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of a One-Time, Bilateral, Intraparenchymal Infusion of SPK-10001 Into the Caudate and Putamen in Participants With Huntington's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Huntington Disease
Keywords: Huntington's Disease
SPK-10001
Adult-onset HD
HD
Rare Disease
Chorea
Movement Disorder
Spark Therapeutics
Cognition
Gene Therapy
AAV
mHTT
Lead sponsor: Spark Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-14
Enrollment: 53
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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/exclusion criteria apply.

Primary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to approximately 5 years
measure: Severity of TEAEs
timeFrame: Day 1 up to approximately 5 years
measure: Change from Baseline in Unified Huntington's Disease Rating Scale (UHDRS®) Total Functional Capacity (TFC) Score
timeFrame: Baseline, Month 24
Secondary outcomes:
measure: Change from Baseline in Motor Symptom Progression Based on Huntington's Disease Digital Motor Score (HDDMS)
timeFrame: Baseline, Months 12, 18, and 24
measure: Change from Baseline in Composite UHDRS (cUHDRS) Score
timeFrame: Baseline, Months 12, 18, and 24
measure: Change from Baseline in UHDRS TFC Score
timeFrame: Baseline, Months 12 and 18
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati/Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
References: