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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 : October 3, 2019
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
John Guy, University of Miami

Tracking Information
First Submitted Date  ICMJE June 6, 2014
First Posted Date  ICMJE June 11, 2014
Last Update Posted Date October 3, 2019
Study Start Date  ICMJE July 2014
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2014)
Assessment of Primary Endpoint - Toxicity [ Time Frame: 1 year ]
Incidence of local and general adverse events and Serious Adverse Events
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02161380 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of an Adeno-associated Virus Vector for Gene Therapy of Leber's Hereditary Optic Neuropathy
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leber's Hereditary Optic Neuropathy
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: 1(Chronic)
    injection of scAAV2-P1ND4v2
    Interventions:
    • 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)
  • Experimental: 2(Acute)
    injection of scAAV2-P1ND4v2
    Interventions:
    • Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
    • Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
    • Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
  • Experimental: 3(Presymptomatic)
    injection of scAAV2-P1ND4v2
    Interventions:
    • Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
    • Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
    • Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 22, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2014)
27
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: JOHN GUY, MD 302-326-6036 jguy@med.miami.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02161380
Other Study ID Numbers  ICMJE 20140248
1U10EY023558-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party John Guy, University of Miami
Study Sponsor  ICMJE John Guy
Collaborators  ICMJE National Eye Institute (NEI)
Investigators  ICMJE
Principal Investigator: JOHN GUY, MD Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136
PRS Account University of Miami
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP