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

Study Overview
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Brief Summary
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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
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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)

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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: LX1001


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Previously administered LX1001<br>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 | Biological: LX1001<br>* Gene therapy<br>* Other names: AAVrh.10hAPOE2;|

What is the study measuring?
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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 |