Phase 1 Clinical Study of the Port Delivery System with ranibizumab for continuous treatment of neovascular age-related macular degeneration

Abstract

Purpose : To evaluate safety, clinical benefit, pharmacokinetics (PK), and integrity of the Port Delivery System with ranibizumab (PDS) in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

Methods : This was a prospective, open-label, phase 1 study of 20 treatment-naïve patients enrolled at a single center. PDS implant containing 25 µL of ranibizumab 10 mg/mL surgically implanted at pars plana; refilled when clinically indicated. Primary endpoint: adverse events (AEs). Other outcomes: best-corrected visual acuity (BCVA), implant refill frequency, ranibizumab serum PK, and implant integrity.

Results : Most common treatment-related AEs: conjunctival hyperemia (95% of patients), vitreous hemorrhage (VH; 25%), hyphema (20%). No VH observed in 10 patients enrolled after refinement of surgical instrumentation and training. Of 76 treatment-related AEs, 66 were mild. Four serious AEs in 3 patients (all within 1 month of implantation) included endophthalmitis with decreased BCVA (1 eye; returning to baseline by month 2) and decreased BCVA with VH (2 eyes; 1 returned to baseline BCVA by month 10; 1 had BCVA 12 letters below baseline at month 36). Mean (95% confidence interval [CI]) BCVA improvement at month 12 is shown in Fig 1. Mean (range [95% CI]) refills/patient was 4.1 (0-11 [2.9-5.3]); median (interquartile range) time to first refill was 3 (2-3) months. Mean serum ranibizumab concentration for 10 patients the 8 weeks after PDS implantation is shown in Fig 2. Analysis of 6 explanted PDS implants did not indicate a change in drug release performance.

Conclusions : This first in-human study of PDS demonstrated its proof of concept and feasibility for treating nAMD. Along with informing phase 2 trial procedures, this study provides unique information about visual and anatomic outcomes and ranibizumab PK in treatment-naïve eyes, a population not included in subsequent phase 2 and 3 trials. Results of the phase 1 and 2 trials suggest PDS has potential to provide sustained clinical benefits in nAMD patients, while reducing overall care burden.

This is a 2020 ARVO Annual Meeting abstract.

 

Fig 1 Mean BCVA change from baseline in efficacy-evaluable patients. n = 18 except ^*n = 17, ^†n = 16. ETDRS = Early Treatment Diabetic Retinopathy Study

 

Fig 2 Mean serum ranibizumab concentration in 10 patients 8 weeks after PDS implantation. Dashed line represents limit of quantitation (15 pg/mL)