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

Phase 1

Recruiting

• Conditions: Alzheimer Disease
• Interventions: Biological: LX1001

• Registration Number: NCT05400330
• Lead Sponsor: Lexeo Therapeutics

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 Cohort 3 only).

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 3 ascending doses (1.4 × 1010, 4.4 × 1010, 1.4 × 1011gene copy \[gc\]/mL CSF) as per droplet digital polymerase chain reaction methodology, with each group consisting of approximately n=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 Timeline

• Study First Submitted: 2022-05-27
• Study First Submitted QC: 2022-05-27
• Study First Posted: 2022-06-01
• Study Start: 2023-05-08
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-13
• Last Update Posted: 2023-11-15
• Primary Completion: 2028-11
• Study Completion: 2028-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Participants who received LX1001 in study LX1001-01

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Previously administered LX1001	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 3 ascending doses (1.4 × 1010, 4.4 × 1010, 1.4 × 1011 gene copy \[gc\]/mL CSF) as per droplet digital polymerase chain reaction methodology, with each group consisting of approximately n=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

Primary Outcome Measures

Name	Time	Method
Incidence of serious adverse events	260 weeks	All incidents of serious adverse events will be collected
Incidence of treatment emergent adverse events	260 weeks	All emergent adverse events will be collected

Trial Locations

Locations (2)

PPD- Orlando Research Unit; 🇺🇸 Orlando, Florida, United States

Duke University; 🇺🇸 Durham, North Carolina, United States