Clinical trial NCT05541627: A Study to Evaluate AB-1001 Striatal Administration in Adults With Early Manifest Huntington's Disease
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Huntington Disease
Keywords: Huntington's Disease
Early Manifest Huntington's Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Gene Therapy
AAV (adeno-associated virus)
Viral Vector
Cholesterol 24-Hydroxylase
CYP46A1
AB-1001
Lead sponsor: AskBio Inc
Sponsor class: INDUSTRY
First posted: 2022-09-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose-Limiting Toxicities (DLTs), Treatment-Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs)
timeFrame: Through Week 52
Secondary outcomes:
measure: Anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI
timeFrame: At Week 52
measure: Composite Unified Huntington Disease Rating Scale (cUHDRS)
timeFrame: At Week 52
measure: Mutant Huntingtin protein (mHTT)
timeFrame: At Week 52
measure: Neurofilament light chain (NfL)
timeFrame: At Week 52
measure: 24OH cholesterol
timeFrame: At Week 52
measure: Magnetic resonance spectroscopy (MRS) metabolic profile
timeFrame: At Week 52
measure: Positron emission tomography (PET) fluoro-deoxyglucose (FDG) striatal profile
timeFrame: At Week 52
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut du Cerveau (ICM), Hôpital La Pitié Salpêtrière APHP
state: Ile-de-France
Study officials:
References: