Clinical trial
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
Name
20140248
Description
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.
Trial arms
Trial start
2014-07-14
Estimated PCD
2023-03-31
Trial end
2024-03-31
Status
Active (not recruiting)
Phase
Early phase I
Treatment
injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL
Arms:
1 Chronic Bilateral Severe Vision Loss, 2 Acute Bilateral Severe Vision Loss, 3 Acute Unilateral Severe Vision Loss
injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL
Arms:
1 Chronic Bilateral Severe Vision Loss, 2 Acute Bilateral Severe Vision Loss, 3 Acute Unilateral Severe Vision Loss
injection of scAAV2-P1ND4v2 2.4 X10e10vg (High)
injection of Total Volume of each intravitreal injection is 100 µL
Arms:
1 Chronic Bilateral Severe Vision Loss
injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL
Arms:
1 Chronic Bilateral Severe Vision Loss, 2 Acute Bilateral Severe Vision Loss, 3 Acute Unilateral Severe Vision Loss
Size
28
Primary endpoint
Assessment of Primary Endpoint - Toxicity
3 year
Eligibility criteria
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 28, 'type': 'ACTUAL'}}
Updated at
2023-12-08
1 organization
1 product
1 indication
Organization
Byron LamProduct
scAAV2-P1ND4v2Indication
Leber's Hereditary Optic Neuropathy