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

Leber's Hereditary Optic Neuropathy Clinical Trial

— LHON  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02161380
• Other study ID #: 20140248
• Secondary ID: 1U10EY023558-01A
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 14, 2014
• Est. completion date: March 31, 2024

Study information

• Verified date: December 2023
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leber's Hereditary Optic Neuropathy
• Optic Atrophy, Hereditary, Leber
• Optic Nerve Diseases

Intervention

Drug:
• injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low),
injection of Total Volume of each intravitreal injection is 200 µL
• injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med)
injection of Total Volume of each intravitreal injection is 200 µL
• injection of scAAV2-P1ND4v2 2.4 X10e10vg (High)
injection of Total Volume of each intravitreal injection is 100 µL
• injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher)
injection of Total Volume of each intravitreal injection is 100 µL

Locations

Country	Name	City	State
United States	Bascom Palmer Eye Institute, University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Byron Lam	National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Feuer WJ, Schiffman JC, Davis JL, Porciatti V, Gonzalez P, Koilkonda RD, Yuan H, Lalwani A, Lam BL, Guy J. Gene Therapy for Leber Hereditary Optic Neuropathy: Initial Results. Ophthalmology. 2016 Mar;123(3):558-70. doi: 10.1016/j.ophtha.2015.10.025. Epub — View Citation

Guy J, Feuer WJ, Davis JL, Porciatti V, Gonzalez PJ, Koilkonda RD, Yuan H, Hauswirth WW, Lam BL. Gene Therapy for Leber Hereditary Optic Neuropathy: Low- and Medium-Dose Visual Results. Ophthalmology. 2017 Nov;124(11):1621-1634. doi: 10.1016/j.ophtha.2017 — View Citation

Lam BL, Feuer WJ, Davis JL, Porciatti V, Yu H, Levy RB, Vanner E, Guy J. Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups. Am J Ophthalmol. 2022 Sep;241:262-271. doi: 10.1016/j.ajo.2022.02.023. — View Citation

Lam BL, Feuer WJ, Porciatti V, Davis JL, Zheng DD, Vanner EA, Savatovsky EJ, Alba DE, Guy J. Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures. Am J Ophthalmol. 2023 Sep 15;257:113-128 — View Citation

Porciatti V, Alba DE, Feuer WJ, Davis J, Guy J, Lam BL. The Relationship Between Stage of Leber's Hereditary Optic Neuropathy and Pattern Electroretinogram Latency. Transl Vis Sci Technol. 2022 Mar 2;11(3):31. doi: 10.1167/tvst.11.3.31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Primary Endpoint - Toxicity	Incidence of local and general adverse events and Serious Adverse Events	3 year
Secondary	Assessment of Secondary Endpoint - Safety & Efficacy	visual acuity change from baseline 2	3 year

External Links

•   Bascom Palmer News