Leber Herediter Optik Nöropatinin Gen Tedavisi İçin Adeno-İlişkili Virüs Vektörünün Güvenlilik Çalışması

Sade dilde özet

Bu doz artırım çalışması, uygun Leber herediter optik nöropati (Leber's Hereditary Optic Neuropathy, LHON) hastalarında mitokondriye yönlendirilen ND4 gen tedavisinin adeno-ilişkili viral vektörle (scAAV2-P1ND4v2) uygulanmasının güvenliğini değerlendirmiştir. Dört farklı doz düzeyi (düşükten en yükseğe) incelenmiştir. Faz 1 (Phase 1) çalışmaya, 15 yaş ve üzerinde, mitokondriyal DNA'da G11778A mutasyonu doğrulanmış ve görme ile retina işlev testlerini yapabilecek katılımcılar alınmıştır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

Faz 1 (Phase 1)

Durum

Tamamlandı

Sponsor

Byron Lam

Müdahale

injection of scAAV2-P1ND4v2 1.18x10e9 vg (Low), (AAV-ND4), injection of scAAV2-P1ND4v2 5.81 X10e9 vg (Med) (AAV-ND4), injection of scAAV2-P1ND4v2 2.4 X10e10vg (High) (AAV-ND4), injection of scAAV2-P1ND4v2 1.0 X10e11vg (Higher) (AAV-ND4)

Başlangıç

14.07.2014

Tahmini bitiş

31.03.2025

Ülkeler

United States

Merkezler

• Miami, United States

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

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.