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

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ClinicalTrials.gov Identifier: NCT02161380
Recruitment Status : Recruiting
First Posted : June 11, 2014
Last Update Posted : January 25, 2018
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
John Guy, University of Miami

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 5.00x10e9 vg (Low), Drug: injection of scAAV2-P1ND4v2 2.46X10e10 vg (Med) Drug: injection of scAAV2-P1ND4v2 1.0X10e11vg (High) Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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
Study Start Date : July 2014
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019


Arm Intervention/treatment
Experimental: 1(Chronic)
injection of scAAV2-P1ND4v2
Drug: injection of scAAV2-P1ND4v2 5.00x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 2.46X10e10 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 1.0X10e11vg (High)
injection of Total Volume of each intravitreal injection is 200 µL

Experimental: 2(Acute)
injection of scAAV2-P1ND4v2
Drug: injection of scAAV2-P1ND4v2 5.00x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 2.46X10e10 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 1.0X10e11vg (High)
injection of Total Volume of each intravitreal injection is 200 µL

Experimental: 3(Presymptomatic)
injection of scAAV2-P1ND4v2
Drug: injection of scAAV2-P1ND4v2 5.00x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 2.46X10e10 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL

Drug: injection of scAAV2-P1ND4v2 1.0X10e11vg (High)
injection of Total Volume of each intravitreal injection is 200 µL




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



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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.

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


Contacts
Contact: JOHN GUY, MD 302-326-6036 jguy@med.miami.edu

Locations
United States, Florida
Bascom Palmer Eye Institute, University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: JOHN GUY, MD    305-326-6036    jguy@miami.edu   
Contact: Phillip Gonzalez, CCRP    305-482-4739    jpgonzalez@med.miami.edu   
Principal Investigator: JOHN GUY, MD         
Sponsors and Collaborators
John Guy
National Eye Institute (NEI)
Investigators
Principal Investigator: JOHN GUY, MD Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136

Additional Information:
Publications of Results:
Responsible Party: John Guy, Professor of Neuro-ophthalmology, University of Miami
ClinicalTrials.gov Identifier: NCT02161380     History of Changes
Other Study ID Numbers: 20140248
1U10EY023558-01A1 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2014    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018

Keywords provided by John Guy, University of Miami:
Gene therapy
Mitochondrial Genes
Leber's
AAV2 Viral vectors

Additional relevant MeSH terms:
Optic Nerve Diseases
Optic Atrophy, Hereditary, Leber
Cranial Nerve Diseases
Nervous System Diseases
Eye Diseases
Optic Atrophies, Hereditary
Optic Atrophy
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases