TY - JOUR
T1 - The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration
T2 - Results from the Randomized Phase 2 Ladder Clinical Trial
AU - Campochiaro, Peter A.
AU - Marcus, Dennis M.
AU - Awh, Carl C.
AU - Regillo, Carl
AU - Adamis, Anthony P.
AU - Bantseev, Vladimir
AU - Chiang, Yawen
AU - Ehrlich, Jason S.
AU - Erickson, Signe
AU - Hanley, William D.
AU - Horvath, Joshua
AU - Maass, Katie F.
AU - Singh, Natasha
AU - Tang, Fan
AU - Barteselli, Giulio
N1 - Funding Information:
Third-party writing assistance (manuscript draft preparation and revision per author direction) was provided by Betsy C. Taylor, PhD, CMPP of Envision Pharma Group and funded by Genentech, Inc.
Publisher Copyright:
© 2019 American Academy of Ophthalmology
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ophtha.2019.03.036
DO - 10.1016/j.ophtha.2019.03.036
M3 - Article
C2 - 30946888
AN - SCOPUS:85065801541
SN - 0161-6420
VL - 126
SP - 1141
EP - 1154
JO - Ophthalmology
JF - Ophthalmology
IS - 8
ER -