Adeno-associated viral vector serotype rh10 containing the human cholesterol 24-hydroxylase gene (human CYP46A1) for Huntington's disease|Early manifest Huntington's disease

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Documented genetic confirmation of pathological CAG expansion in the huntingtin gene ≥ 40"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Striatal MRI volumes per hemisphere compatible with the local delivery of the study drug: Putamen ≥ 2.3 cm3 (per side); Caudate ≥ 1.7 cm3 on Screening MRI."}
• {"criterion_text":"- All HD concomitant medications are stable for at least 30 days prior to screening at the investigator’s discretion."}

Exclusion criteria

• {"criterion_text":"- Subjects with prior metastatic neoplasms"}
• {"criterion_text":"- Subjects with active psychosis"}
• {"criterion_text":"- Subjects with confused state"}
• {"criterion_text":"- Subjects with violent and/or suicidal behavior"}
• {"criterion_text":"- Subjects with prior strokes"}
• {"criterion_text":"- Subjects with intracranial hemorrhage"}
• {"criterion_text":"- Subjects with active infection"}
• {"criterion_text":"- Subjects with contraindication to MRI or gadolinium and any other medical condition that in the investigator’s opinion would interfere with the study conduct and assessments will be excluded."}

Primary endpoints

• {"endpoint_text":"- Incidence of Dose Limiting Toxicities (DLTs), Treatment Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs) through Week 52","definition_or_measurement_approach":"Incidence of DLTs, TEAEs and SAEs assessed through Week 52 (safety/tolerability assessment over 52 weeks)."}

Secondary endpoints

• {"endpoint_text":"- Magnitude and variability of change from baseline in anatomical and volumetric measures of brain regions impacted by HD (caudate, putamen, whole brain volume, grey matter volume, white matter volume, ventricular volume) as assessed by MRI at Week 52","definition_or_measurement_approach":"Change from baseline in anatomical and volumetric brain measures assessed by MRI at Week 52."}
• {"endpoint_text":"- Change from baseline in the Unified Huntington’s Disease Rating Scale composite score [cUHDRS: Total Motor Score (TMS), Total Functional Capacity (TFC), Symbol Digit Modalities Test (SDMT) and Stroop Word Reading (SWRT)] at Week 52","definition_or_measurement_approach":"Change from baseline in cUHDRS composite score components at Week 52."}
• {"endpoint_text":"- Change from baseline in blood and cerebrospinal fluid (CSF) mHTT, Neurofilament light chain (NfL), and 24-OH cholesterol at Week 52","definition_or_measurement_approach":"Biomarker concentration changes in blood and CSF for mHTT, NfL and 24-OH cholesterol at Week 52."}
• {"endpoint_text":"- Change from baseline in Magnetic Resonance Spectroscopy (MRS) metabolic profile (measuring lactate, N-acetyl aspartate, creatine, choline, glutamate, glutamine, glutathione, taurine, and myo-inositol) at Week 52","definition_or_measurement_approach":"Change from baseline in MRS metabolic profile measuring listed metabolites at Week 52."}
• {"endpoint_text":"- Change from baseline in Positron Emission Tomography (PET) Fluoro-deoxyglucose (FDG) striatal profile at Week 52","definition_or_measurement_approach":"Change from baseline in FDG-PET striatal profile at Week 52."}

France

Earliest CTIS Part Ii Submission Date

16-01-2024

Latest Decision Or Authorization Date

24-11-2025

Processing Time Days

678

Number Of Sites

1

Number Of Participants

18

Primary sponsor

Full Name

AskBio France

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"United States","full_name":"Metabolon Inc.","duties_or_roles":"lipidomics analyses, metabolic profile","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Ixico Technologies Limited","duties_or_roles":"Central Imaging Service","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Zindametrix Pty Limited","duties_or_roles":"Cognitive and behavioural tests.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Sweden","full_name":"Olink Proteomics AB","duties_or_roles":"proteomics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Bayer AG","duties_or_roles":"Statistical analysis; Medical Writing; Medical Expertise; Data Management; E-data capture; Safety Reporting","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Institut Du Cerveau Et De La Moelle Epiniere","duties_or_roles":"","organisation_type":"Educational Institution"}