Gene Therapy in Neovascular Age-related Macular Degeneration: Three-Year Follow-up of a Phase 1 Randomized Dose Escalation Trial

Autor: Aaron L. Magno, Martyn A. French, Ian J. Constable, Samuel B. Barone, Elizabeth Rakoczy, Mark S. Blumenkranz, Steven D. Schwartz, Mariapia A. Degli-Esposti, Chooi May Lai
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Pars plana
medicine.medical_specialty
Time Factors
Visual acuity
genetic structures
medicine.medical_treatment
Visual Acuity
Vitrectomy
Retina
Injections
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Ophthalmology
medicine
Clinical endpoint
Humans
Aged
Aged
80 and over
Dose-Response Relationship
Drug
business.industry
Receptors
Interleukin-1
Genetic Therapy
Macular degeneration
medicine.disease
Interleukin-1 Receptor-Like 1 Protein
Choroidal Neovascularization
eye diseases
Treatment Outcome
030104 developmental biology
Choroidal neovascularization
medicine.anatomical_structure
Wet Macular Degeneration
030221 ophthalmology & optometry
Female
sense organs
medicine.symptom
Ranibizumab
business
Tomography
Optical Coherence
Follow-Up Studies
medicine.drug
Zdroj: American Journal of Ophthalmology. 177:150-158
ISSN: 0002-9394
DOI: 10.1016/j.ajo.2017.02.018
Popis: Purpose To assess the safety of rAAV.sFlt-1 subretinal injection in neovascular age-related macular degeneration (wet AMD) over 36 months. Design Phase 1 dose escalation trial. Methods Eight subjects with advanced, treatment-experienced wet AMD were randomly assigned (3:1) to treatment and non–gene therapy control groups. Eligible subjects were ≥65 years, had wet AMD, and had best-corrected visual acuity (BCVA) 10/200 to 20/80 in the study eye and 20/200 or better in the other eye. Three of the treatment group subjects received low-dose (1 × 10 10 vector genomes) and 3 high-dose (1 × 10 11 vector genomes) rAAV.sFLT-1 via subretinal injection. Study monitoring was monthly to the primary endpoint at month 12 and then protocol-driven follow-up study visits were conducted at months 18 and 36. All subjects received intravitreal ranibizumab at baseline and at week 4, and retreatment injections at subsequent visits based on prespecified criteria for active wet AMD. The primary endpoint was ocular and systemic safety, but exploratory data including BCVA, retinal center point thickness, and the number of ranibizumab retreatments at and between study visits were also analyzed. Results Six of the 8 subjects completed the 36-month study. Subretinal injection with pars plana vitrectomy was well tolerated in this cohort. No ocular or systemic safety signals were observed during the long-term follow-up period. Exploratory data analysis suggests stability of wet AMD over the 36-month period. Conclusions Subretinal delivery of rAAV.sFLT-1 was well tolerated and demonstrated a favourable safety profile through month 36. Thus, rAAV.sFLT-1 could be safely considered for future evaluation in the treatment of wet AMD.
Databáze: OpenAIRE
Externí odkaz: