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

Long-Term Follow-Up to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Biological: LX1001

Detailed Description

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 to assess the safety and efficacy parameters (~208 weeks within this study)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • PPD- Orlando Research Unit
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who received LX1001 in study LX1001-01

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Previously administered LX1001; 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; Gene therapy; Other Names: AAVrh.10hAPOE2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Lexeo Therapeutics
• Investigators: Study Director: Lexeo Clinical Trials, Lexeo Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: May 27, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: LX1001-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No