Elizabeth P Rakoczy1, Aaron L Magno2, Chooi-May Lai3, Cora M Pierce2, Mariapia A Degli-Esposti3, Mark S Blumenkranz4, Ian J Constable5. 1. Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia. Electronic address: elizabeth.rakoczy@uwa.edu.au. 2. Lions Eye Institute, Nedlands, Western Australia, Australia. 3. Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia. 4. Byers Eye Institute at Stanford, Palo Alto, CA, USA. 5. Lions Eye Institute, Nedlands, Western Australia, Australia; Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia.
Abstract
PURPOSE: To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration. DESIGN: Phase 1/2a clinical trial. METHODS: Patients were prospectively randomized into control (n = 13) and GT (n = 24) groups. GT patients received 1X1011vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2 months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12 months, GT patients were divided into 2 groups: HD-1 (n = 14), requiring <2, and HD-2 (n = 10), requiring >2 retreatments. RESULTS: Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1 patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2 patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2 patients, and 51% of HD-1 patients showed maintenance of baseline visual acuity. Four HD-1 patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant. CONCLUSIONS: Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.
RCT Entities:
PURPOSE: To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration. DESIGN: Phase 1/2a clinical trial. METHODS:Patients were prospectively randomized into control (n = 13) and GT (n = 24) groups. GT patients received 1X1011vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2 months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12 months, GT patients were divided into 2 groups: HD-1 (n = 14), requiring <2, and HD-2 (n = 10), requiring >2 retreatments. RESULTS: Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2patients, and 51% of HD-1patients showed maintenance of baseline visual acuity. Four HD-1patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant. CONCLUSIONS: Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.
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