Long-Term Follow-up of Gene Therapy for APOE4 Homozygote Alzheimer's Disease

NCT05400330 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LX1001-02
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this long-term follow-up study is to assess the long-term safety profile of APOE4 homozygote participants who were administered gene therapy (LX1001) for the treatment of Alzheimer's disease in Study LX100101. A secondary objective is to assess the biomarker as shown by the conversion of CSF APOE isoforms from APOE4 to APOE2-APOE4. Additional secondary outcomes include amyloid PET scan, CSF markers (including Aβ42, Aβ42/Aβ40 ratio T--tau, and P-tau), and quantitative MRI (and other biomarkers that may be informative for this therapeutic approach). Other secondary objectives include instruments to assess cognitive and clinical AD and to evaluate if treatment with AAVrh.10hAPOE2 improves brain tau pathology with tau PET scan (LX1001-01 Cohorts 3 and 4 only).

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment emergent adverse events

  All emergent adverse events will be collected

  260 weeks

• Incidence of serious adverse events

  All incidents of serious adverse events will be collected

  260 weeks

Study Arms (1)

Previously administered LX1001

EXPERIMENTAL

This is a long-term follow-up study to evaluate the safety following LX1001, a gene therapy, for participants who are APOE4 homozygotes with clinical diagnoses varying from MCI or dementia due to AD who have previously received LX1001. Study LX1001-01 was designed to assess the safety of LX1001 at 4 ascending doses (1.4 × 1010, 4.4 × 1010, 1.4 × 1011 gene copy \[gc\]/mL CSF and 1.4 x 1014 \[fixed dose\]) as per droplet digital polymerase chain reaction methodology, with each group consisting of approximately n=3-5 individuals for a total of approximately 15 participants for the entire study. In this study, participants who have received LX1001 in the parent protocol (LX1001-01) will be followed for up to 260 weeks post gene therapy administration

Biological: LX1001

Interventions

LX1001 BIOLOGICAL

Gene therapy

Also known as: AAVrh.10hAPOE2

Previously administered LX1001

Eligibility Criteria

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

You may qualify if:

• Participants who received LX1001 in study LX1001-01

You may not qualify if:

• Participants with any clinically significant medical condition that, in the opinion of the investigator, would pose a risk to participant safety
• Participants who agree not to post their personal medical data in relation to this study or any study information online, including social media sites, until all participants have completed all LX1001 clinical studies, including long-term follow-up.

Sponsors & Collaborators

• Lexeo Therapeutics: lead

Study Sites (2)

PPD- Orlando Research Unit

Orlando, Florida, 32806, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 1, 2022
• Study Start: May 8, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)