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Franco Recchia, Steven Blotner, Natasha Singh, Giulio Barteselli, Shamika Gune; Ladder Phase 2 Trial of the Port Delivery System With Ranibizumab (PDS) for Neovascular AMD: End of Study Results. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1155.
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The PDS is an investigational drug delivery system designed for the continuous intravitreal release of ranibizumab through a permanent indwelling intraocular implant. The safety and efficacy of the PDS for the treatment of neovascular age-related macular degeneration (nAMD) was evaluated in the phase 2 Ladder trial.
The Ladder trial (NCT02510794) compared the PDS filled with 3 different customized ranibizumab formulations with monthly intravitreal ranibizumab 0.5 mg. The primary endpoint was time to first implant refill according to protocol-defined criteria assessed when the last enrolled patient completed the month (M) 9 visit. Secondary outcomes included mean change from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT). All patients continued on assigned study treatment until they were eligible to roll over into the Portal extension study (NCT03683251).
Ladder evaluated 220 patients, with 58, 62, 59, and 41 patients in the PDS 10, 40, and 100 mg/mL and monthly intravitreal ranibizumab 0.5 mg arms, respectively. The mean time on study was 22.1M (range, 10.8M-37.6M) for all PDS patients. The median time to first required refill was 8.7M, 13.0M, and 15.8M for the PDS 10, 40, and 100 mg/mL arms, respectively. In the PDS 100 mg/mL arm, 59.4% of patients went ≥12M without meeting refill criteria. In PDS 100 mg/mL patients who met implant refill criteria at least once, the median time to first and second refills was consistent: first refill, 8.8M (n=31/59); second refill, 8.8M (n=19/31). At M22 in the PDS 100 mg/mL and monthly ranibizumab 0.5 mg arms, respectively, the mean BCVA change from baseline was +2.9 and +2.7 letters, and 87.5% and 88.9% of patients maintained vision (lost <5 letters from baseline). Mean CFT change from baseline excluding pigment epithelial detachment height was generally similar between the PDS 100 mg/mL and monthly ranibizumab 0.5 mg arms. No dose-related serious AEs were observed.
Ladder end of study efficacy and safety outcomes were consistent with the primary analysis. PDS 100 mg/mL continuously maintained vision and anatomic outcomes through a mean time on study of 22M. The optimized implant insertion procedure and refill procedure were generally well tolerated. The PDS has potential to reduce high intravitreal treatment burden and improve real-world clinical outcomes.
This is a 2020 ARVO Annual Meeting abstract.
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