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A Study to Evaluate BV-101 Striatal Administration in Adults With Early Manifest Huntington's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05541627
Recruitment Status : Recruiting
First Posted : September 15, 2022
Last Update Posted : October 18, 2022
Sponsor:
Information provided by (Responsible Party):
Asklepios Biopharmaceutical, Inc. ( Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio) )

Study Description
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Brief Summary:
A Phase I/II Dose-Finding Study to Evaluate Striatal Administration of BV-101 in Adults with Early Manifest Huntington's Disease

Condition or disease Intervention/treatment Phase
Huntington Disease Genetic: BV-101 Gene Therapy Phase 1 Phase 2

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 BV-101 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase I/II Dose Finding Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Striatal Administration of BV-101 in Adult Subjects With Early Manifest Huntington's Disease (HD)
Actual Study Start Date : October 12, 2022
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
Low-dose of BV-101
 Genetic: BV-101 Gene Therapy
One-time intracerebral bilateral injections of BV-101 (AAVrh10.CAG.hCYP46A1), an adeno-associated viral vector serotype Rh10 containing the human cholesterol 24-hydroxylase gene
Other Name: AAVrh10.CAG.hCYP46A1
Experimental: Cohort 2
High-dose of BV-101
 Genetic: BV-101 Gene Therapy
One-time intracerebral bilateral injections of BV-101 (AAVrh10.CAG.hCYP46A1), an adeno-associated viral vector serotype Rh10 containing the human cholesterol 24-hydroxylase gene
Other Name: AAVrh10.CAG.hCYP46A1


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Dose-Limiting Toxicities (DLTs), Treatment-Emergent Adverse Events (TEAEs), and Serious Adverse Events (SAEs) [ Time Frame: Through Week 52 ]
    The incidence of DLTs, TEAEs, and SAEs will be measured according to protocol specifications.


Secondary Outcome Measures :
  1. Anatomical and volumetric measures of brain regions impacted by HD as assessed by MRI [ Time Frame: At Week 52 ]
    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

  2. Composite Unified Huntington Disease Rating Scale (cUHDRS) [ Time Frame: At Week 52 ]
    The change from baseline in the cUHDRS will be measured (a higher score indicates better functioning)

  3. Mutant Huntingtin protein (mHTT) [ Time Frame: At Week 52 ]
    The change from baseline in mHTT in blood and cerebrospinal fluid (CSF) will be measured

  4. Neurofilament light chain (NfL) [ Time Frame: At Week 52 ]
    The change from baseline in blood and CSF NfL will be measured

  5. 24OH cholesterol [ Time Frame: At Week 52 ]
    The change from baseline in blood and CSF 24OH cholesterol will be measured

  6. Magnetic resonance spectroscopy (MRS) metabolic profile [ Time Frame: At Week 52 ]
    Change from baseline in MRS metabolic profile

  7. Positron emission tomography (PET) fluoro-deoxyglucose (FDG) striatal profile [ Time Frame: At Week 52 ]
    Change from baseline in PET FDG striatal profile


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05541627


Contacts
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Contact: AskFirst Patient Engagement askfirst@askbio.com

Locations
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France
Institut du Cerveau (ICM), Hôpital La Pitié Salpêtrière APHP Recruiting
Paris, Ile-de-France, France, 75013
Contact: Hortense Hurmic       hortense.hurmic@icm-institute.org   
Sponsors and Collaborators
Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio)
More Information
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Responsible Party: Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio)
ClinicalTrials.gov Identifier: NCT05541627    
Other Study ID Numbers: ASK-HD-01-CS-101
First Posted: September 15, 2022    Key Record Dates
Last Update Posted: October 18, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Asklepios Biopharmaceutical, Inc. ( Brainvectis, a subsidiary of Asklepios BioPharmaceutical, Inc. (AskBio) ):
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
BV-101
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
 Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders