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

Sponsor

Byron Lam (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02161380

Collaborator

National Eye Institute (NEI) (NIH)

Enrollment

Location

Arms

103.6

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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 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)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group 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

Actual Study Start Date :

Jul 14, 2014

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Assessment of Primary Endpoint - Toxicity [3 year]
Incidence of local and general adverse events and Serious Adverse Events

Secondary Outcome Measures

Assessment of Secondary Endpoint - Safety & Efficacy [3 year]
visual acuity change from baseline 2

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 15 or older;
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;
Ability to perform tests of visual and retinal function;
Ability to comply with research procedures;
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.

Exclusion Criteria:

Unwilling or unable to give consent,
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.
Optic disc drusen on exam or in previous history.
Ocular diseases or visual dysfunction conditions other than refractive error (e.g. amblyopia, glaucoma, etc.) in the eye selected for the injection.
Previous eye surgery in the eye selected for injection.
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

Any laboratory screening test that meets the abnormality criteria stated above can be repeated once between Baseline one to Baseline 2.

Type I diabetes or the presence of diabetic retinopathy
History of neurodegenerative conditions (e.g. multiple sclerosis, neuromyelitis optica, Parkinson disease)
History of autoimmune conditions (e.g. systemic lupus erythematosus)
History of 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.
Allergy to pupil dilating drops or narrow angles precluding safe dilation.
No Light Perception (NLP) vision in either eye.