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Gene Therapy for APOE4 Homozygote of Alzheimer's Disease

Sponsor
Lexeo Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03634007
Collaborator
Alzheimer's Drug Discovery Foundation (Other), Weill Medical College of Cornell University (Other)
15
Enrollment
2
Locations
3
Arms
58.6
Anticipated Duration (Months)
7.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial is an open label, dose-ranging study designed to evaluate gene therapy to treat patients who are APOE4 homozygotes with clinical diagnosis varying from mild cognitive impairment due to Alzheimer's, mild dementia due to Alzheimer's disease, and moderate dementia due to Alzheimer's disease.

Condition or Disease Intervention/Treatment Phase
  • Biological: LX1001
 Phase 1

Detailed Description

All subjects will have evidence of amyloid plaque by nuclear Positron emission tomography (PET scan) and cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer's disease. The study will assess the safety and toxicity of intrathecal administration of AAVrh.10hAPOE2, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the complementary deoxyribonucleic acid (cDNA) coding for human apolipoprotein E2 (APOE2), directly to the central nervous system (CNS)/ CSF of APOE4 homozygotes with Alzheimer's disease. The study will establish a maximum tolerable dose and generate preliminary evidence regarding whether direct administration of AAVrh.10hAPOE2 to the CNS of those Alzheimer's patients will lead to conversion of the APOE protein isoforms in the CSF of APOE4 homozygotes from APOE4 to APOE2-APOE4.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A 52-Week, Multicenter, Phase 1 Open-label Study to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease
Actual Study Start Date :
Nov 6, 2019
Anticipated Primary Completion Date :
Sep 23, 2023
Anticipated Study Completion Date :
Sep 23, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort I: 5.0 x 10^10 gc/mL CSF

5.0 x 10^10 gc/mL CSF of LX1001

Biological: LX1001
LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
Other Names:
  • AAVrh.10hAPOE2

    		•
    Experimental: Cohort II: 1.6 x 10^11 gc/mL CSF

    1.6 x 10^11 gc/mL CSF of LX1001

    Biological: LX1001
    LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
    Other Names:
  • AAVrh.10hAPOE2

    		•
    Experimental: Cohort III: 5.0 x 10^11 gc/mL CSF

    5.0 x 10^11 gc/mL CSF of LX1001

    Biological: LX1001
    LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
    Other Names:
  • AAVrh.10hAPOE2

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of participants with treatment-emergent adverse events and serious adverse events [1 year]

      Adverse events categorized and graded

    2. The proportion of participants with treatment-emergent adverse events and serious adverse events at each dosage [1 year]

      Adverse events categorized and graded per study drug dose

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • APOE4 homozygotes

    • Males and females, age 50 or older

    • Willing and able to provide informed consent (or consent provided by legally authorized representative)

    • Mild cognitive impairment due to Alzheimer's disease, or clinical diagnosis of mild to moderate dementia due to Alzheimer's disease

    • Evidence of amyloid plaques by nuclear PET scan and cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer's disease

    • Serum neutralizing anti-AAVrh10 titer <1:100

    • No evidence of active infection of any type, including hepatitis virus (A, B or C) or human immunodeficiency virus (HIV-1 and HIV-2)

    • Fertile or infertile individuals; it will be recommended that fertile individuals utilize barrier birth control measures to prevent pregnancy for the duration of the study

    • Individuals not receiving experimental medications or participating in another experimental protocol for at least 4 weeks prior to entry to the study

    • Participants who agree not to post their personal data related to the study on social media.

    Exclusion Criteria:

    • Individuals receiving receiving systemic corticosteroids, other immunosuppressive medications, Aduhelm (aducanumab), other immunosuppressive medications, or anti-coagulant medications (other than aspirin)

    • Individuals who do not fit the American Journal of Neuroradiology recommendations for image guided spinal procedures

    • Presence of other significant medical or neurological conditions may disqualify the subject from participation in this study, particularly those which would create an unacceptable risk to receiving the AAVrh.10APOE2 vector, for example, malignancy, heart failure, liver or renal failure, or HIV positive.

    • Evidence of ongoing infection

    • Elevated white blood cell count, temperature >38.5ĚŠ C, infiltrate on chest x-ray

    • Prior or concurrent participation in any gene and/or cell therapy

    • Any condition, disorder, or abnormal laboratory test findings at screening which, in the judgment of the investigator, would interfere with the individual's ability to comply with all study requirements, or would require the administration of treatment during the study that could potentially affect the interpretation of the study data, or would place the individual at an unacceptable risk by his/her participation in the study

    • Individuals who cannot participate in MRI, PET and CSF studies

    • Individuals who cannot undergo study-related procedures without general anesthesia

    • More than 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis, or evidence of a prior macrohemorrhage

    • Are pregnant or nursing

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 PPD Development Orlando Florida United States 32806
    2 Weill Cornell Medicine New York New York United States 10065-4870

    Sponsors and Collaborators

    • Lexeo Therapeutics
    • Alzheimer's Drug Discovery Foundation
    • Weill Medical College of Cornell University

    Investigators

    • Study Director: Lexeo Clinical Trials, Lexeo Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Lexeo Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03634007
    Other Study ID Numbers:
    • LX1001-01
    First Posted:
    Aug 16, 2018
    Last Update Posted:
    Jul 13, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    No Results Posted as of Jul 13, 2022