Archway Randomized Phase 3 Trial of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration.

Abstract Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Design Phase 3, open-label, randomized, visual acuity assessor–masked noninferiority (NI) and equivalence trial. Participants Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy. Methods Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/mL with fixed 24-week refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Main Outcome Measures Primary end point was change in best-corrected visual acuity (BCVA) score from baseline averaged over weeks 36 and 40 (NI margin, –4.5 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; equivalence margin, ±4.5 ETDRS letters). Results Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 (PDS Q24W) and 75.5 (monthly ranibizumab) ETDRS letters (Snellen equivalent 20/32). Adjusted mean (standard error) change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 (0.5) ETDRS letters in the PDS Q24W arm and +0.5 (0.6) in the monthly ranibizumab arm (difference, –0.3; 95% confidence interval, –1.7 to 1.1). The PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Out of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest (AESIs) were reported in 47 (19.0%) PDS Q24W and 10 (6.0%) monthly ranibizumab patients. Ocular AESIs in PDS-treated patients included 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in PDS patients occurred within 1 month of implantation. Conclusions Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.