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

Huntington Disease Clinical Trial

Official 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05541627
• Other study ID #: ASK-HD-01-CS-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 12, 2022
• Est. completion date: December 31, 2029

Study information

• Verified date: July 2023
• Source: Asklepios Biopharmaceutical, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This is a Phase I/II, first-in-human, open-label study to evaluate the safety, tolerability, and preliminary efficacy signals in subjects with early manifest HD following treatment with one-time intracerebral bilateral injections of AB-1001 within the striatum (caudate and putamen). This study consists of 2 parts: Dose-Finding Part and Expansion Part; each part consists of 3 phases: Screening Phase (8 weeks, with extension to 12 weeks to accommodate scheduling if needed), Treatment and Initial Follow-Up Phase (52 weeks) and Long-Term Follow-Up Phase (4 years). In the Dose-Finding Part, 2 dose titers will be tested in 3-6 subjects in each cohort. Once a dose is selected based on Dose-Limiting Toxicities, an additional 6 subjects will be enrolled into the Dose Expansion Part.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Genetic:
• AB-1001 Gene Therapy
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

Locations

Country	Name	City	State
France	Institut du Cerveau (ICM), Hôpital La Pitié Salpêtrière APHP	Paris	Ile-de-France

Sponsors (1)

Lead Sponsor	Collaborator
Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI	The magnitude and variability of change from baseline in anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI will be measured	At Week 52
Secondary	Composite Unified Huntington Disease Rating Scale (cUHDRS)	The change from baseline in the cUHDRS will be measured (a higher score indicates better functioning)	At Week 52
Secondary	Mutant Huntingtin protein (mHTT)	The change from baseline in mHTT in blood and cerebrospinal fluid (CSF) will be measured	At Week 52
Secondary	Neurofilament light chain (NfL)	The change from baseline in blood and CSF NfL will be measured	At Week 52
Secondary	24OH cholesterol	The change from baseline in blood and CSF 24OH cholesterol will be measured	At Week 52
Secondary	Magnetic resonance spectroscopy (MRS) metabolic profile	Change from baseline in MRS metabolic profile	At Week 52
Secondary	Positron emission tomography (PET) fluoro-deoxyglucose (FDG) striatal profile	Change from baseline in PET FDG striatal profile	At Week 52