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

December 2, 2023 updated by: Byron Lam

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Bascom Palmer Eye Institute, University of Miami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Primary Endpoint - Toxicity
Time Frame: 3 year
Incidence of local and general adverse events and Serious Adverse Events
3 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of Secondary Endpoint - Safety & Efficacy
Time Frame: 3 year
visual acuity change from baseline 2
3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Byron Lam

Collaborators

National Eye Institute (NEI)

Investigators

  • Principal Investigator: Byron Lam, MD, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2014

Primary Completion (Actual)

March 31, 2023

Study Completion (Estimated)

March 31, 2024

Study Registration Dates

First Submitted

June 6, 2014

First Submitted That Met QC Criteria

June 10, 2014

First Posted (Estimated)

June 11, 2014

Study Record Updates

Last Update Posted (Estimated)

December 8, 2023

Last Update Submitted That Met QC Criteria

December 2, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20140248
  • 1U10EY023558-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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