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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05541627
Other study ID # ASK-HD-01-CS-101
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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