Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration

Charles C. Wykoff, Peter A. Campochiaro, Dante J. Pieramici, Arshad M. Khanani, Shamika Gune, Mauricio Maia, Matts Kågedal, Han Ting Ding, Katie F. Maass

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Ladder was a phase 2 trial that evaluated the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration. Serum and aqueous humor samples were collected to characterize the pharmacokinetics (PK) of ranibizumab delivered through the PDS. Methods: Ladder was a multicenter, randomized, active treatment-controlled, phase 2 clinical trial. Patients with neovascular age-related macular degeneration (n = 220) were randomized (3:3:3:2) to PDS 10 mg/ml, PDS 40 mg/ml, PDS 100 mg/ml, or monthly intravitreal ranibizumab 0.5 mg. Serum PK samples were collected in all arms and analyzed for ranibizumab concentration using an enzyme-linked immunosorbent assay. The main PK analyses were conducted in the PK-evaluable population (n = 68), which excluded patients who received fellow eye intravitreal treatment, supplemental ranibizumab treatment, or had previous treatment with bevacizumab in either eye within 9 months of randomization. Results: In the PDS 10 mg/ml arm, median serum ranibizumab concentrations were below the serum trough concentration (Ctrough; 130 pg/ml) expected with monthly intravitreal ranibizumab 0.5 mg at all time points. In the PDS 40 mg/ml and 100 mg/ml arms, median serum ranibizumab concentrations were above the Ctrough expected with monthly intravitreal ranibizumab 0.5 mg (130 pg/ml) through month 3 and month 12 after implantation, respectively, and remained above the lower limit of quantification through month 15 and month 16 after implantation, respectively. Conclusions: These PK data indicate that the implant in the PDS 100 mg/ml arm maintained ranibizumab concentrations within the range of monthly intravitreal ranibizumab 0.5 mg injections (130–2220 pg/ml) through month 12 after implantation. Trial Registration: ClinicalTrials.gov identifier, NCT02510794.

Original languageEnglish (US)
JournalOphthalmology and Therapy
DOIs
StateAccepted/In press - 2022

Keywords

  • Age-related macular degeneration
  • Implant
  • Neovascular age-related macular degeneration
  • Pharmacokinetics
  • Port Delivery System with ranibizumab
  • Ranibizumab
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology

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