Gene Therapy for Leber's Optic Atrophy

(LHON Trial)

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Byron Lam

Disqualifiers: Pregnancy, Optic disc drusen, Diabetes, Neurodegenerative, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Single administration

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Byron Lam, MD

Principal Investigator

Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136

Are You a Good Fit for This Trial?

This trial is for individuals aged 15 or older with Leber's Hereditary Optic Neuropathy (LHON) and a specific genetic mutation (G11778A). Participants must be in good health, able to perform visual tests, comply with study procedures, and provide informed consent. Exclusions include other eye diseases, severe liver issues, blood disorders, previous eye surgery on the affected eye, pregnancy/nursing women not using contraception, certain systemic or autoimmune diseases.

Inclusion Criteria

Able and willing to provide informed consent before undergoing any study related procedures

Good general health as based on the investigator's assessment of the history, physical examination and laboratory testing performed at the baseline examination

I am 15 years old or older.

Exclusion Criteria

Unable or unlikely to return for scheduled protocol visits

Pregnant or nursing women or unwillingness for subject with childbearing potential to use contraception during the first year of the study

Your liver enzymes or bilirubin levels are too high, or your red blood cell, white blood cell, or platelet counts are too low.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of scAAV2-P1ND4v2 at varying doses to assess safety and tolerability

Single administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including ocular and systemic toxicity assessments

36 months

What Are the Treatments Tested in This Trial?

Interventions

• scAAV2-P1ND4v2

Trial Overview The trial is testing different doses of an injection called scAAV2-P1ND4v2 to treat LHON. There are four dose levels: low, medium-higher and high. The main goal is to check if these injections are safe and do not cause any loss of vision in the treated eyes.

How Is the Trial Designed?

Group I: Medium dose (5.81x10e9 vg) Experimental Treatment 1 Intervention

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.

Group II: Low-dose (1.18x10e9 vg) Experimental Treatment 1 Intervention

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

Group III: Higher dose (1x10e11vg) Experimental Treatment 1 Intervention

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.

Group IV: High dose (2.40x10e10 vg) Experimental Treatment 1 Intervention

Participants with Chronic Bilateral Severe Vision Loss were administered 100 µL of scAAV2-P1ND4v2 containing a dose of 2.40x10e10 vg.

Who Is Running the Clinical Trial?

Byron Lam

Lead Sponsor

Trials

2

Recruited

30+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+