A Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease

NCT05541627 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: ASK-HD-01-CS-101
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I/II Dose-Finding Study to Evaluate Striatal Administration of AB-1001 (previously BV-101) in Adults with Early Manifest Huntington's Disease

Conditions

Huntington Disease

Keywords

Huntington's Disease; Early Manifest Huntington's Disease; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Gene Therapy; AAV (adeno-associated virus); Viral Vector; Cholesterol 24-Hydroxylase; CYP46A1; AB-1001

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-Limiting Toxicities (DLTs), Treatment-Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs)

  The incidence of DLTs, TEAEs, and SAEs will be measured according to protocol specifications.

  Through Week 52

Secondary Outcomes (7)

• Anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI

  At Week 52

• Composite Unified Huntington Disease Rating Scale (cUHDRS)

  At Week 52

• Mutant Huntingtin protein (mHTT)

  At Week 52

• Neurofilament light chain (NfL)

  At Week 52

• 24OH cholesterol

  At Week 52

Study Arms (2)

Cohort 1

EXPERIMENTAL

Low-dose of AB-1001

Genetic: AB-1001 Gene Therapy

Cohort 2

EXPERIMENTAL

High-dose of AB-1001

Genetic: AB-1001 Gene Therapy

Interventions

AB-1001 Gene Therapy GENETIC

One-time intracerebral bilateral injections of AB-1001 (AAVrh10.CAG.hCYP46A1), an adeno-associated viral vector serotype Rh10 containing the human cholesterol 24-hydroxylase gene

Also known as: AAVrh10.CAG.hCYP46A1 (previously BV-101)

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Male or Female subjects between ages 18 and 65 years (both inclusive) at time of consenting, able to provide Informed Consent and able to understand and comply with all study procedures.
• Documented genetic confirmation of pathological CAG expansion in the huntingtin gene ≥40.
• Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and a diagnostic classification level (DCL) of 4, or a DCL of 3 if present with cognitive impairment and clear evidence of disease progression.
• Striatal MRI volumes per hemisphere: Putamen ≥ 2.3 cm3 (per side); Caudate ≥ 1.7 cm3 (per side) on Screening MRI.
• All HD concomitant medications stable for at least 30 days prior to screening at the investigator's discretion.

You may not qualify if:

• Prior or ongoing medical condition, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, would impact subject's safety and compliance with the study procedures.
• Metastatic neoplasms within the five years prior to screening.
• Presence of clinically relevant immunologic, hematologic, hepatic, cardiac, or renal disease at the time of screening as per investigator's clinical judgment.
• Current untreated and unstable depressive disorder or a serious mood disorder requiring hospitalization.
• History of prior suicide attempt or imminent risk of self-harm based on investigator's judgment or with a "yes" answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).
• Patients with history of confirmed stroke, known intracranial neoplasms, vascular malformations, or intracranial hemorrhage.
• Subjects not deemed suitable for the surgical procedure as per the Neurosurgeon's judgment.
• Any history of gene therapy, cell transplantation or any other experimental brain surgery.
• Any RNA or DNA targeted HD specific investigational agents such as antisense oligonucleotides within 6 months prior to screening.
• Subjects unable to tolerate or unwilling to undergo multiple lumbar punctures.
• Participation in any clinical trial of an approved or non-approved investigational drug or intervention within 12 weeks or 5 half-lives whichever is longer prior to treatment.

Sponsors & Collaborators

• AskBio France, SAS, a subsidiary of AskBio Inc.: lead

Study Sites (1)

Institut du Cerveau (ICM), Hôpital La Pitié Salpêtrière APHP

Paris, Île-de-France Region, 75013, France

Location

MeSH Terms

Conditions

Huntington Disease; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Dementia; Chorea; Dyskinesias; Heredodegenerative Disorders, Nervous System; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2022
• First Posted: September 15, 2022
• Study Start: October 12, 2022
• Primary Completion: April 4, 2024
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 14, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)