Pharmacokinetic (PK) Profile of the Port Delivery System With Ranibizumab (PDS) in the Phase 3 Pagoda and Pavilion Trials

Document Type

Conference Proceeding

Publication Date

6-2024

Publication Title

Investigative Ophthalmology and Visual Science

Abstract

Purpose : To characterize the PK profile of ranibizumab 100 mg/mL administered via the PDS (a drug delivery system that includes an ocular implant for continuous delivery of a customized formulation of ranibizumab) in the phase 3 Pagoda trial (NCT04108156; n=634) for diabetic macular edema (DME) and phase 3 Pavilion trial (NCT04503551; n=174) for diabetic retinopathy (DR) without center-involved diabetic macular edema.

Methods : Pagoda compared the PDS with fixed refill-exchanges every 24 weeks (PDS Q24W) vs intravitreal ranibizumab 0.5 mg injections every 4 weeks (RBZ Q4W). Pavilion compared the PDS with fixed refill-exchanges every 36 weeks (PDS Q36W) vs control (clinical monitoring plus supplemental intravitreal ranibizumab 0.5 mg as required). Before PDS implantation, patients received loading doses of intravitreal ranibizumab 0.5 mg injections Q4W. Serum PK and optional aqueous humor (AH) samples were collected at predefined timepoints in both trials. Results presented are for the PK-evaluable populations. Ranibizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (lower limits of quantitation: 15 pg/mL (Pagoda) and 30 pg/mL (Pavilion) for serum, and 20,000 pg/mL for AH).

Results : In Pagoda, PDS Q24W geometric mean (coefficient of variation %) serum ranibizumab concentrations (n=53) at 4 weeks (w) and 24w following implantation were 360 (62.5%) and 262 (47.7%) pg/mL, respectively. AH ranibizumab concentration (n=18) at 24w following implantation was 1.06 (526%) µg/mL and at 12w following first refill-exchange was 2.77 (18.9%) µg/mL. PDS Q24W serum concentrations were below the maximum experienced 1–5 days after a loading dose (1070 [502.9%] pg/mL). PDS Q24W serum and AH concentrations following implantation were above RBZ Q4W trough concentrations (Ctrough) (serum, n=53; AH, n=19) at 4w and 40w (serum, 62.4 [318.6%] and 39.4 [302.8%] pg/mL, respectively; AH, 0.428 [281.2%] and 0.568 [876.9%] µg/mL, respectively).
In Pavilion, PDS Q36W serum ranibizumab concentrations (n=24) at 4w, 24w, and 36w following implantation were 383 (71.3%), 213 (38.3%), and 143 (74.2%) pg/mL, respectively.

Conclusions : PDS continuously released ranibizumab at steady concentrations above intravitreal ranibizumab 0.5 mg injection Ctrough over Q24W and Q36W refill intervals. Thus, the PK exposure range with PDS treatment is consistent between trials for DME and DR.

Volume

65

Issue

7

First Page

6234

Comments

Association for Research in Vision and Ophthalmology Annual Meeting, ARVO 2024, May 5-9, 2024, Seattle, WA

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