Gene Therapy for APOE4 Homozygote of Alzheimer's Disease
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03634007 |
Recruitment Status :
Recruiting
First Posted : August 16, 2018
Last Update Posted : November 20, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Alzheimer Disease Early Onset Alzheimer Disease | Biological: AAVrh.10hPOE2 vector | 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: | Gene Therapy for APOE4 Homozygote of Alzheimer's Disease |
Actual Study Start Date : | October 6, 2019 |
Estimated Primary Completion Date : | December 2020 |
Estimated Study Completion Date : | December 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: Cohort I: 8.0 x 10^10 gc/kg
Subjects will receive 8.0 x 10^10 gc/kg of AAVrh.10hAPOE2.
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Biological: AAVrh.10hPOE2 vector
AAVrh.10hAPOE2 is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2). |
Experimental: Cohort II: 2.5 x 10^11 gc/kg
Subjects will receive 2.5 x 10^11 gc/kg of AAVrh.10hAPOE2.
|
Biological: AAVrh.10hPOE2 vector
AAVrh.10hAPOE2 is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2). |
Experimental: Cohort III: 8.0 x 10^11 gc/kg
Subjects will receive 8.0 x 10^11 gc/kg of AAVrh.10hAPOE2.
|
Biological: AAVrh.10hPOE2 vector
AAVrh.10hAPOE2 is a serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human apolipoprotein E2 (APOE2). |
- Safety of AAVrh.10hAPOE2 gene therapy, as measured by number of adverse events or serious adverse events [ Time Frame: 2 years ]
- Maximum tolerated dose of intracisternal delivery of AAVrh.10hAPOE2 gene therapy to APOE4 homozygotes with Alzheimer's disease [ Time Frame: 2 years ]

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 very mild to severe dementia due to Alzheimer's disease
- Evidence of amyloid plaques by nuclear PET scan and/or cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer's disease
- Serum neutralizing anti-AAVrh10 titer <10-2
- 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
Exclusion Criteria:
- Individuals receiving corticosteroids, 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 procedures9
- 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 >38.5̊C, 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

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: Grace W Mammen, BA, CCRP | 646-962-2672 | gwm2004@med.cornell.edu |
United States, New York | |
Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine | Recruiting |
New York, New York, United States, 10065-4870 | |
Contact: Denesy Mancenido, BA 646-962-5583 dem2026@med.cornell.edu | |
Contact: Grace Mammen, BA gwm2004@med.cornell.edu |
Principal Investigator: | Ronald G Crystal, MD | Weill Cornell Medicine |
Responsible Party: | Weill Medical College of Cornell University |
ClinicalTrials.gov Identifier: | NCT03634007 History of Changes |
Other Study ID Numbers: |
1806019315 |
First Posted: | August 16, 2018 Key Record Dates |
Last Update Posted: | November 20, 2019 |
Last Verified: | November 2019 |
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 |