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

May 23, 2025 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

The study is a dose-escalation study, phase 1. The objective of this proposed clinical trial is to evaluate the safety of mitochondrially targeted ND4 gene therapy with the adeno-associated viral vector in appropriate LHON patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this dose-escalation study is to assess the safety and tolerability of scAAV2-P1ND4v2 (abbreviated as AAV-ND4) gene replacement therapy in subjects confirmed with the G11778A mutation in mtDNA responsible for Leber's Hereditary Optic Neuropathy. Ocular and systemic toxicity will be assessed following vector administration to determine if there are adverse changes that may be associated with vector administration.

This first-in-man (FIM) clinical trial will assess the safety, tolerability, and potential efficacy of a single intravitreal injection in patient groups reflecting the acute, pre-symptomatic, and chronic stages and manifestation of the LHON disease.

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's disease)
  10. History of autoimmune conditions (e.g. systemic lupus erythematosus)
  11. Systemic diseases having ocular manifestations likely to confound assessment of study results. 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.
  12. Allergy to pupil dilating drops or narrow angles precluding safe dilation.
  13. 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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low-dose (1.18x10e9 vg)

Participants with Chronic Bilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 1.18x10e9 vg.

Participants with Acute Bilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 1.18x10e9 vg.

Participants with Acute Unilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 1.18x10e9 vg
Drug: injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL
Other Names:
  • AAV-ND4
Experimental: Medium dose (5.81x10e9 vg)

Participants with Chronic Bilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 5.81x10e9 vg.

Participants with Acute Bilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 5.81x10e9 vg.

Participants with Acute Unilateral Severe Vision Loss were administered 200 µL of scAAV2-P1ND4v2 containing a dose of 5.81x10e9 vg.
Drug: injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL
Other Names:
  • AAV-ND4
Experimental: High dose (2.40x10e10 vg)
Participants with Chronic Bilateral Severe Vision Loss were administered 100 µL of scAAV2-P1ND4v2 containing a dose of 2.40x10e10 vg.
Drug: injection of scAAV2-P1ND4v2 2.4 X10e10vg (High)
injection of Total Volume of each intravitreal injection is 100 µL
Other Names:
  • AAV-ND4
Experimental: Higher dose (1x10e11vg)

Participants with Chronic Bilateral Severe Vision Loss were administered 100 µL of scAAV2-P1ND4v2 containing a dose of 1x10e11vg.

Participants with Acute Bilateral Severe Vision Loss were administered 100 µL of scAAV2-P1ND4v2 containing a dose of 1x10e11vg.

Participants with Acute Unilateral Severe Vision Loss were administered 100 µL of scAAV2-P1ND4v2 containing a dose of 1x10e11vg.
Drug: injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL
Other Names:
  • AAV-ND4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Treatment Related Adverse Events
Time Frame: 3 years
Number of treatment-related adverse events will be assessed as per investigator with respective to relationship to the investigative product.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best-corrected Visual Acuity
Time Frame: up to 36 months after treatment

Best-corrected visual acuity(BCVA) was tested using the ETDRS Chart. The LogMAR visual acuity scale was adapted from the ETDRS chart to facilitate statistical analysis.

Longitudinal analyses of BCVA changes at months 12, 24, and 36 versus baseline 2 were performed.
up to 36 months after treatment

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 (Actual)

March 31, 2025

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 (Actual)

June 5, 2025

Last Update Submitted That Met QC Criteria

May 23, 2025

Last Verified

May 1, 2025

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.

Clinical Trials on Leber's Hereditary Optic Neuropathy

Clinical Trials on injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahrain

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe