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Safety Study of an Adeno-associated Virus Vector for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02161380
Recruitment Status : Active, not recruiting
First Posted : June 11, 2014
Last Update Posted : March 24, 2023
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
Byron Lam, University of Miami

Study Description
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Brief Summary:

Hypotheses:

The primary hypothesis being tested is that there will be no toxicity resulting in loss of vision to no light perception in injected eyes.


Condition or disease Intervention/treatment Phase
Leber's Hereditary Optic Neuropathy Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low), Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med) Drug: injection of scAAV2-P1ND4v2 2.4 X10e10vg (High) Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher) Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA
Actual Study Start Date : July 14, 2014
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 1 Chronic Bilateral Severe Vision Loss
injection of scAAV2-P1ND4v2
 Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 2.4 X10e10vg (High)
injection of Total Volume of each intravitreal injection is 100 µL

Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL
Experimental: 2 Acute Bilateral Severe Vision Loss
injection of scAAV2-P1ND4v2
 Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL
Experimental: 3 Acute Unilateral Severe Vision Loss
injection of scAAV2-P1ND4v2
 Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL


Outcome Measures
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Primary Outcome Measures :
  1. Assessment of Primary Endpoint - Toxicity [ Time Frame: 3 year ]
    Incidence of local and general adverse events and Serious Adverse Events


Secondary Outcome Measures :
  1. Assessment of Secondary Endpoint - Safety & Efficacy [ Time Frame: 3 year ]
    visual acuity change from baseline 2


Eligibility Criteria
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Information from the National Library of Medicine

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.


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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 15 or older;
  2. Patients with LHON and the G11778A mitochondrial DNA mutation. A previous CLIA certified genetic lab result showing the LHON G11778A mutation will be accepted for inclusion;
  3. Ability to perform tests of visual and retinal function;
  4. Ability to comply with research procedures;
  5. Able and willing to provide informed consent before undergoing any study related procedures.
  6. Good general health as based on the investigator's assessment of the history, physical examination and laboratory testing performed at the baseline examination.

Exclusion Criteria:

  1. Unwilling or unable to give consent,
  2. Unable or unlikely to return for scheduled protocol visits
  3. Pregnant or nursing women or unwillingness for subject with childbearing potential to use contraception during the first year of the study.
  4. Optic disc drusen on exam or in previous history.
  5. Ocular diseases or visual dysfunction conditions other than refractive error (e.g. amblyopia, glaucoma, etc.) in the eye selected for the injection.
  6. Previous eye surgery in the eye selected for injection.

  7. Aspartate transaminase (AST)/alanine transaminase (ALT) >5.0 x upper limit of normal (ULN); Total bilirubin >3 x ULN; Hemoglobin < 8 g/dL; neutrophil count <1.0 x 109/L; or platelet count < 50 x 109/L

    a) Any laboratory screening test that meets the abnormality criteria stated above can be repeated once between Baseline one to Baseline 2.

  8. Type I diabetes or the presence of diabetic retinopathy
  9. History of neurodegenerative conditions (e.g. multiple sclerosis, neuromyelitis optica, Parkinson disease)
  10. History of autoimmune conditions (e.g. systemic lupus erythematosus)
  11. History of systemic diseases having ocular manifestations likely to confound assessment of study results.
  12. History of cancer within five years other than localized basal or squamous cell carcinoma not near the orbital area. Patients with a prior history of cancer will need documentation from their cancer specialist that the cancer was cured at least 5 years before study entry.
  13. Allergy to pupil dilating drops or narrow angles precluding safe dilation.
  14. No Light Perception (NLP) vision in either eye.
Contacts and Locations
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Information from the National Library of Medicine

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): NCT02161380


Locations
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United States, Florida
Bascom Palmer Eye Institute, University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
Byron Lam
National Eye Institute (NEI)
Investigators
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Principal Investigator: Byron Lam, MD Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136
More Information
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Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Byron Lam, Greene Professor of Ophthalmology, University of Miami
ClinicalTrials.gov Identifier: NCT02161380    
Other Study ID Numbers: 20140248
1U10EY023558-01A1 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2014    Key Record Dates
Last Update Posted: March 24, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Byron Lam, University of Miami:
Gene therapy
Mitochondrial Genes
Leber's
AAV2 Viral vectors
Additional relevant MeSH terms:
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Optic Nerve Diseases
Optic Atrophy, Hereditary, Leber
Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Optic Atrophies, Hereditary
Optic Atrophy
 Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases