[HTML][HTML] The port delivery system with ranibizumab for neovascular age-related macular degeneration: results from the randomized phase 2 ladder clinical trial

PA Campochiaro, DM Marcus, CC Awh, C Regillo… - Ophthalmology, 2019 - Elsevier
PA Campochiaro, DM Marcus, CC Awh, C Regillo, AP Adamis, V Bantseev, Y Chiang…
Ophthalmology, 2019Elsevier
Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab
(PDS) for neovascular age-related macular degeneration (nAMD) treatment. Design Phase
2, multicenter, randomized, active treatment–controlled clinical trial. Participants Patients
diagnosed with nAMD within 9 months who had received 2 or more prior anti–vascular
endothelial growth factor intravitreal injections and were responsive to treatment. Methods
Patients were randomized 3: 3: 3: 2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 …
Purpose
To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment.
Design
Phase 2, multicenter, randomized, active treatment–controlled clinical trial.
Participants
Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti–vascular endothelial growth factor intravitreal injections and were responsive to treatment.
Methods
Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections.
Main Outcome Measures
Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety.
Results
The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters, +5.0 ETDRS letters, and +3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging.
Conclusions
In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.
Elsevier