AzTrials
AzTrials

Alzheimer DiseasePhase 1/2NCT03634007

Gene Therapy for APOE4 Homozygote of Alzheimer's Disease

A Phase 1/2 study testing LX1001 in people with Alzheimer Disease and Early Onset Alzheimer Disease, run by Lexeo Therapeutics at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This clinical trial is an open label, dose-ranging study designed to evaluate gene therapy to treat patients who are APOE4 homozygotes with clinical diagnosis varying from mild cognitive impairment due to Alzheimer's, mild dementia due to Alzheimer's disease, and moderate dementia due to Alzheimer's disease. Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
LX1001
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
4 sitesUnited States
Study dates
6 Nov 2019to 7 Nov 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • APOE4 homozygotes
  • Willing and able to provide informed consent (or consent provided by a legally authorized representative)
  • Clinical diagnosis of mild cognitive impairment due to Alzheimer's disease or mild to moderate dementia due to Alzheimer's disease
  • Evidence of 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)
Show all 9Show fewer
  • 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 into the study
  • Participants who agree not to post their personal data related to the study on social media.

Who cannot join

  • Individuals receiving systemic immunosuppressant or corticosteroid therapy other than protocol-specified, are receiving a monoclonal anti-amyloid therapy (example, Aduhelm™ (aducanumab), Leqembi™ (lecanemab-irmb) or unable to wash out from anti-coagulant medications.
  • Individuals who do not fit the American Journal of Neuroradiology recommendations for image-guided spinal procedures
  • Presence of other significant medical, psychiatric, or neurological conditions may disqualify the participant from participation in this study, particularly those which would create an unacceptable risk of receiving the LX1001-01 vector, for example, malignancy, heart failure, liver or renal failure, or HIV positive.
  • Elevated white blood cell count, temperature >38.5° C, infiltrate on chest x-ray. Note: Repeat of these examinations during the screening period is permitted to confirm eligibility
  • 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 unacceptable risk by his/her participation in the study
Show all 11Show fewer
  • Individuals who cannot participate in magnetic resonance imaging, amyloid and tau PET scans, and CSF studies
  • Individuals who cannot undergo study-related procedures without general anesthesia (other than who need general anesthesia for the gene therapy administration)
  • 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 macro hemorrhage on screening MRI
  • Individuals with a history of clinically significant hypersensitivity or contraindication as judged by the investigator, to any component of the study drug formulation or to any drugs used in this study (examples are corticosteroids and proton-pump inhibitors)
  • Are pregnant or nursing

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Duke University

    Durham, North Carolina, 27708

  • K2 Medical Research

    Maitland, Florida, 32751

  • Weill Cornell Medicine

    New York, New York, 10021

  • PPD- Orlando Research Unit

    Orlando, Florida, 32806

Other trials in United States

About this study

Official title: A 52-Week, Multicenter, Phase 1/2 Open-label Study to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease

This clinical trial is an open label, dose-ranging study designed to evaluate gene therapy to treat patients who are APOE4 homozygotes with clinical diagnosis varying from mild cognitive impairment due to Alzheimer's, mild dementia due to Alzheimer's disease, and moderate dementia due to Alzheimer's disease.

Read the detailed description

The study will assess the safety and toxicity of intrathecal administration of AAVrh.10hAPOE2 (LX1001), serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the complementary deoxyribonucleic acid (cDNA) coding for human apolipoprotein E2 (APOE2), directly to the central nervous system (CNS)/ CSF of APOE4 homozygotes with Alzheimer's disease. All subjects will have evidence of cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer's disease. The study will establish a maximum tolerable dose and generate preliminary evidence regarding whether direct administration of LX1001 to the CNS of those Alzheimer's patients will lead to conversion of the APOE protein isoforms in the CSF of APOE4 homozygotes from APOE4 to APOE2-APOE4.

Being tested
LX1001
Keywords
Alzheimer Disease, APOE4 homozygotes
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LX1001Biological

    Also called AAVrh.10hAPOE2

    LX1001 is a serotype rh.10 AAV gene transfer vector expressing the cDNA coding for human APOE2.

Study groups in NCT03634007
Study groupRoleWhat they receive
Cohort 1: 1.4 x 10^10 gc/mL CSFExperimentalParticipants will receive 1.4 x 10^10 gc/mL CSF of LX1001.
Receives: Biological: LX1001
Cohort 2: 4.4 x 10^10 gc/mL CSFExperimentalParticipants will receive 4.4 x 10^10 gc/mL CSF of LX1001.
Receives: Biological: LX1001
Cohort 3: 1.4 x 10^11 gc/mL CSFExperimentalParticipants will receive 1.4 x 10^11 gc/mL CSF of LX1001.
Receives: Biological: LX1001
Cohort 4: 1.4 x 10^14 gc (fixed dose)ExperimentalParticipants will receive 1.4 x 10^14 gc (fixed dose; approximately 3.4 × 10^11 gc/mL CSF based on an average CSF volume of 409 mL) of LX1001.
Receives: Biological: LX1001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of participants with treatment-emergent adverse events and serious adverse events

    Adverse events categorized and graded

    Measured: 1 year

  2. The proportion of participants with treatment-emergent adverse events and serious adverse events at each dosage

    Adverse events categorized and graded per study drug dose

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2018
  2. Study start6 Nov 2019
  3. Primary completion7 Nov 2024
  4. Study completion7 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03634007
Sponsor's protocol ID
LX1001-01
Status last verified
Oct 2025
First submitted
3 Aug 2018
Last updated
20 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • De BP, Cram S, Lee H, Rosenberg JB, Sondhi D, Crystal RG, Kaminsky SM. Assessment of Residual Full-Length SV40 Large T Antigen in Clinical-Grade Adeno-Associated Virus Vectors Produced in 293T Cells. Hum Gene Ther. 2023 Aug;34(15-16):697-704. doi: 10.1089/hum.2023.032.

    PubMed 37171121

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LX1001 in people with Alzheimer Disease and Early Onset Alzheimer Disease, run by Lexeo Therapeutics at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with treatment-emergent adverse events and serious adverse events (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03634007, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in