Gene Therapy for APOE4 Homozygote of Alzheimer's Disease
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ClinicalTrials.gov Identifier: NCT03634007 |
Recruitment Status :
Recruiting
First Posted : August 16, 2018
Last Update Posted : April 5, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Alzheimer Disease Early Onset Alzheimer Disease | Biological: LX1001 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 15 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A 52-Week, Multicenter, Phase 1 Open-label Study to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease |
Actual Study Start Date : | November 6, 2019 |
Estimated Primary Completion Date : | September 23, 2023 |
Estimated Study Completion Date : | September 23, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: Cohort I: 5.0 x 10^10 gc/mL CSF
5.0 x 10^10 gc/mL CSF of LX1001
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Biological: LX1001
LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
Other Name: AAVrh.10hAPOE2 |
Experimental: Cohort II: 1.6 x 10^11 gc/mL CSF
1.6 x 10^11 gc/mL CSF of LX1001
|
Biological: LX1001
LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
Other Name: AAVrh.10hAPOE2 |
Experimental: Cohort III: 5.0 x 10^11 gc/mL CSF
5.0 x 10^11 gc/mL CSF of LX1001
|
Biological: LX1001
LX1001 (AAVrh.10hAPOE2) is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2).
Other Name: AAVrh.10hAPOE2 |
- Proportion of participants with treatment-emergent adverse events and serious adverse events [ Time Frame: 1 year ]
- The proportion of participants with treatment-emergent AEs and SAEs at each dosage [ Time Frame: 1 year ]
- Change from baseline in APOE2-APOE4 isoforms [ Time Frame: 1 year ]
- Change from baseline in brain amyloid plaques as assessed by PET scan [ Time Frame: 1 year ]
- Change from baseline in levels of CSF biomarkers [ Time Frame: 1 year ]
- Change from baseline in hippocampal and entorhinal cortex volumes as assessed by brain magnetic resonance imaging (MRI) [ Time Frame: 1 year ]
- Change from baseline in Clinical Dementia Rating Global and Sum of Boxes (CDR-SB) [ Time Frame: 1 year ]
- Change from baseline in the Mini Mental State Examination (MMSE) [ Time Frame: 1 year ]
- Change from baseline in the Alzheimer's Disease Assessment Scale - Cognition 13 (ADAS-Cog 13) [ Time Frame: 1 year ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- APOE4 homozygotes
- Males and females, age 50 or older
- Willing and able to provide informed consent (or consent provided by legally authorized representative)
- Mild cognitive impairment due to Alzheimer's disease, or clinical diagnosis of mild to moderate dementia due to Alzheimer's disease
- Evidence of amyloid plaques by nuclear PET scan and cerebrospinal fluid (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 to the study
- Participants who agree not to post their personal data related to the study on social media.
Exclusion Criteria:
- Individuals receiving receiving systemic corticosteroids, other immunosuppressive medications, Aduhelm (aducanumab), other immunosuppressive medications, or anti-coagulant medications (other than aspirin)
- Individuals who do not fit the American Journal of Neuroradiology recommendations for image guided spinal procedures
- Presence of other significant medical or neurological conditions may disqualify the subject from participation in this study, particularly those which would create an unacceptable risk to receiving the AAVrh.10APOE2 vector, for example, malignancy, heart failure, liver or renal failure, or HIV positive.
- Evidence of ongoing infection
- Elevated white blood cell count, temperature >38.5̊ C, infiltrate on chest x-ray
- 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 an unacceptable risk by his/her participation in the study
- Individuals who cannot participate in MRI, PET and CSF studies
- Individuals who cannot undergo study-related procedures without general anesthesia
- 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 macrohemorrhage
- Are pregnant or nursing

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03634007
Contact: Lexeo Clinical Trials | +1 212-547-9879 | clinicaltrials@lexeotx.com | |
Contact: Lexeo Clinical Trials |
United States, Florida | |
PPD Development | Recruiting |
Orlando, Florida, United States, 32806 | |
Contact: Juan Alvarez juan.alvarez@ppd.com | |
United States, New York | |
Weill Cornell Medicine | Recruiting |
New York, New York, United States, 10065-4870 | |
Contact: Haley Bowe hab40007@med.cornell.edu |
Study Director: | Lexeo Clinical Trials | Lexeo Therapeutics |
Responsible Party: | Lexeo Therapeutics |
ClinicalTrials.gov Identifier: | NCT03634007 |
Other Study ID Numbers: |
1806019315 |
First Posted: | August 16, 2018 Key Record Dates |
Last Update Posted: | April 5, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |