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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 August 2024
• Main ID: NCT05541627
• Date of registration: 13/09/2022
• Prospective Registration: Yes
• Primary sponsor: Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio)
• Public title: A Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease
• Scientific title: An Open-Label Phase I/II Dose Finding Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Striatal Administration of AB-1001 in Adult Subjects With Early Manifest Huntington's Disease (HD)
• Date of first enrolment: October 12, 2022
• Target sample size: 5
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05541627
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

France

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

Key Exclusion Criteria:

- 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.


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Huntington Disease

Intervention(s)

Genetic: AB-1001 Gene Therapy

Primary Outcome(s)

Incidence of Dose-Limiting Toxicities (DLTs), Treatment-Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs) [Time Frame: Through Week 52]

Secondary Outcome(s)

Neurofilament light chain (NfL) [Time Frame: At Week 52]

Composite Unified Huntington Disease Rating Scale (cUHDRS) [Time Frame: At Week 52]

Positron emission tomography (PET) fluoro-deoxyglucose (FDG) striatal profile [Time Frame: At Week 52]

Anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI [Time Frame: At Week 52]

Magnetic resonance spectroscopy (MRS) metabolic profile [Time Frame: At Week 52]

24OH cholesterol [Time Frame: At Week 52]

Mutant Huntingtin protein (mHTT) [Time Frame: At Week 52]

Secondary ID(s)

ASK-HD-01-CS-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors