A Randomized Study of SPK-10001 Gene Therapy in Participants With Huntington's Disease

NCT06826612 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SPK-10001-101XN45617
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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

Study Arms (2)

SPK-10001

EXPERIMENTAL

Genetic: SPK-10001

Placebo Surgery Control

OTHER

Other: Placebo Surgery Control

Interventions

SPK-10001 GENETIC

Specified dose on specified days

SPK-10001

Placebo Surgery Control OTHER

Placebo Surgery procedure for SPK-10001

Placebo Surgery Control

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

University of Cincinnati/Cincinnati Children's Hospital

Cincinnati, Ohio, 45221, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43221, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pittsburg

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Huntington Disease; Rare Diseases; Chorea; Movement Disorders

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Dyskinesias; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Clinical Trials

  Hoffmann-LaRoche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: SPK-10001-101 https://forpatients.roche.com/

CONTACT

888-662-6728; global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 14, 2025
• Study Start: February 21, 2025
• Primary Completion (Estimated): January 12, 2035
• Study Completion (Estimated): January 12, 2035
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)