Gene Therapy for APOE4 Homozygote of Alzheimer's Disease

NCT03634007 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: LX1001-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

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.

Conditions

Alzheimer Disease; Early Onset Alzheimer Disease

Keywords

Alzheimer Disease; APOE4 homozygotes

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with treatment-emergent adverse events and serious adverse events

  Adverse events categorized and graded

  1 year

• The proportion of participants with treatment-emergent adverse events and serious adverse events at each dosage

  Adverse events categorized and graded per study drug dose

  1 year

Study Arms (4)

Cohort 1: 1.4 x 10^10 gc/mL CSF

EXPERIMENTAL

Participants will receive 1.4 x 10\^10 gc/mL CSF of LX1001.

Biological: LX1001

Cohort 2: 4.4 x 10^10 gc/mL CSF

EXPERIMENTAL

Participants will receive 4.4 x 10\^10 gc/mL CSF of LX1001.

Biological: LX1001

Cohort 3: 1.4 x 10^11 gc/mL CSF

EXPERIMENTAL

Participants will receive 1.4 x 10\^11 gc/mL CSF of LX1001.

Biological: LX1001

Cohort 4: 1.4 x 10^14 gc (fixed dose)

EXPERIMENTAL

Participants will receive 1.4 x 10\^14 gc (fixed dose; approximately 3.4 × 10\^11 gc/mL CSF based on an average CSF volume of 409 mL) of LX1001.

Biological: LX1001

Interventions

LX1001 BIOLOGICAL

LX1001 is a serotype rh.10 AAV gene transfer vector expressing the cDNA coding for human APOE2.

Also known as: AAVrh.10hAPOE2

Cohort 1: 1.4 x 10^10 gc/mL CSF; Cohort 2: 4.4 x 10^10 gc/mL CSF; Cohort 3: 1.4 x 10^11 gc/mL CSF; Cohort 4: 1.4 x 10^14 gc (fixed dose)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• APOE4 homozygotes
• Willing and able to provide informed consent (or consent provided by a legally authorized representative)
• Clinical diagnosis of mild cognitive impairment due to Alzheimer's disease or mild to moderate dementia due to Alzheimer's disease
• Evidence of 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 into the study
• Participants who agree not to post their personal data related to the study on social media.

You may not qualify if:

• Individuals receiving systemic immunosuppressant or corticosteroid therapy other than protocol-specified, are receiving a monoclonal anti-amyloid therapy (example, Aduhelm™ (aducanumab), Leqembi™ (lecanemab-irmb) or unable to wash out from anti-coagulant medications.
• Individuals who do not fit the American Journal of Neuroradiology recommendations for image-guided spinal procedures
• Presence of other significant medical, psychiatric, or neurological conditions may disqualify the participant from participation in this study, particularly those which would create an unacceptable risk of receiving the LX1001-01 vector, for example, malignancy, heart failure, liver or renal failure, or HIV positive.
• Elevated white blood cell count, temperature \>38.5° C, infiltrate on chest x-ray. Note: Repeat of these examinations during the screening period is permitted to confirm eligibility
• 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 unacceptable risk by his/her participation in the study
• Individuals who cannot participate in magnetic resonance imaging, amyloid and tau PET scans, and CSF studies
• Individuals who cannot undergo study-related procedures without general anesthesia (other than who need general anesthesia for the gene therapy administration)
• 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 macro hemorrhage on screening MRI
• Individuals with a history of clinically significant hypersensitivity or contraindication as judged by the investigator, to any component of the study drug formulation or to any drugs used in this study (examples are corticosteroids and proton-pump inhibitors)
• Are pregnant or nursing

Sponsors & Collaborators

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

Study Sites (4)

K2 Medical Research

Maitland, Florida, 32751, United States

Location

PPD- Orlando Research Unit

Orlando, Florida, 32806, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

Related Publications (1)

• De BP, Cram S, Lee H, Rosenberg JB, Sondhi D, Crystal RG, Kaminsky SM. Assessment of Residual Full-Length SV40 Large T Antigen in Clinical-Grade Adeno-Associated Virus Vectors Produced in 293T Cells. Hum Gene Ther. 2023 Aug;34(15-16):697-704. doi: 10.1089/hum.2023.032.

  PMID: 37171121 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Lexeo Clinical Trials

  Lexeo Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 16, 2018
• Study Start: November 6, 2019
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)