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
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
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
Institut du Cerveau (ICM), Hôpital La Pitié Salpêtrière APHP
Paris, Île-de-France Region, France
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.
Time frame: Through Week 52
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
Time frame: At Week 52
Composite Unified Huntington Disease Rating Scale (cUHDRS)
The change from baseline in the cUHDRS will be measured (a higher score indicates better functioning)
Time frame: At Week 52
Mutant Huntingtin protein (mHTT)
The change from baseline in mHTT in blood and cerebrospinal fluid (CSF) will be measured
Time frame: At Week 52
Neurofilament light chain (NfL)
The change from baseline in blood and CSF NfL will be measured
Time frame: At Week 52
24OH cholesterol
The change from baseline in blood and CSF 24OH cholesterol will be measured
Time frame: At Week 52
Magnetic resonance spectroscopy (MRS) metabolic profile
Change from baseline in MRS metabolic profile
Time frame: At Week 52
Positron emission tomography (PET) fluoro-deoxyglucose (FDG) striatal profile
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Change from baseline in PET FDG striatal profile
Time frame: At Week 52