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

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

The main goal of this study is to evaluate the safety, tolerability, and preliminary efficacy of SPK-10001 in participants with Huntington's Disease.

Study Overview

• Status: Recruiting
• Conditions: Huntington Disease
• Intervention / Treatment: Genetic: SPK-10001; Other: Placebo Surgery Control

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: SPK-10001-101 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Dr. Samuel Frank, MD; Phone Number: (617) 667-2355; Email: skrishfi@bidmc.harvard.edu
      • Contact: Suzanne Welcher; Phone Number: (617) 667-2355; Email: skrishfi@bidmc.harvard.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Recruiting
      • University of Cincinnati/Cincinnati Children's Hospital
      • Contact: Andrew Duker, MD
      • Contact: Lauren Wingler; Phone Number: 513-558-0222; Email: winglelh@ucmail.uc.edu
    • Columbus, Ohio, United States, 43221
      • Recruiting
      • Ohio State University
      • Contact: Nicole Vrettos; Phone Number: 614-366-8642; Email: Nicole.Vrettos@osumc.edu
      • Contact: Sandra Kostyk, MD, PhD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPK-10001	Genetic: SPK-10001; Specified dose on specified days
Other: Placebo Surgery Control	Other: Placebo Surgery Control; Placebo Surgery procedure for SPK-10001

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-LaRoche

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2025
• Primary Completion (Estimated): January 12, 2035
• Study Completion (Estimated): January 12, 2035

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 14, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Cognition; AAV; Huntington's Disease; HD; Movement Disorder; Chorea; mHTT; Rare Disease; SPK-10001; Adult-onset HD; Spark Therapeutics
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Rare Diseases; Movement Disorders; Huntington Disease; Chorea
• Other Study ID Numbers: SPK-10001-101; XN45617 (Other Identifier: Hoffmann - LaRoche)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No