Clinical Trials Logo

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
See also
  Status Clinical Trial Phase
Terminated NCT03052712 - Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies N/A
Not yet recruiting NCT04429230 - Non-invasive Brain Stimulation in Huntington's Disease N/A
Recruiting NCT05032196 - Study of WVE-003 in Patients With Huntington's Disease Phase 1/Phase 2
Recruiting NCT03599076 - Wearable Sensors for Quantitative Assessment of Motor Impairment in Huntington's Disease Huntington's Disease
Terminated NCT04617860 - Open-label Extension Study to Evaluate the Safety and Tolerability of WVE-120102 in Patients With Huntington's Disease Phase 1/Phase 2
Completed NCT05748288 - Development of the Virtual Unified Huntington's Disease Rating Scale
Not yet recruiting NCT05360082 - Comparison Between [11C]UCB-J and [18F]SynVest-1 PET in HD.
Not yet recruiting NCT04370470 - Development of Assessments for Later Stage HD
Recruiting NCT01834053 - Safety and Efficacy of Bone Marrow Derived MNCs for Treatment of Cells for the Treatment of Hunting Tons Chorea. Phase 1/Phase 2
Completed NCT01357681 - Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease (ETON-Study) Phase 2
Completed NCT01458470 - A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease Phase 2
Completed NCT00980694 - Bioavailability of Ubiquinol in Huntington Disease Phase 1
Completed NCT00146211 - TREND-HD - A Trial of Ethyl-EPA (Miraxion™) in Treating Mild to Moderate Huntington's Disease Phase 3
Recruiting NCT01412125 - Study of Biomarkers That Predict the Evolution of Huntington's Disease N/A
Completed NCT00075140 - Family Health After Predictive Huntington Disease (HD) Testing Phase 3
Recruiting NCT04818060 - Preparing for Prevention of Huntington's Disease (PREVENT-HD)
Active, not recruiting NCT04698551 - NIPD on cffDNA for Triplet Repeat Diseases
Not yet recruiting NCT04301726 - Efficacy of Deutetrabenazine to Control Symptoms of Dysphagia Associated With HD Phase 1
Completed NCT03421327 - Genetic Risk: Whether, When, and How to Tell Adolescents
Recruiting NCT03296176 - Metabolomic Study in Huntington's Disease (METABO-HD) N/A