June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Phase 1 Clinical Study of the Port Delivery System with ranibizumab for continuous treatment of neovascular age-related macular degeneration
Author Affiliations & Notes
  • Anat Loewenstein
    Tel Aviv Medical Center, Tel Aviv, Israel
  • Guna Laganovska
    Pauls Stradinš Clinical University Hospital, Riga, Latvia
  • Neil M Bressler
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Juris Vanags
    Pauls Stradinš Clinical University Hospital, Riga, Latvia
  • Yair Alster
    Azura Ophthalmics, Tel Aviv, Israel
  • Eugene De Juan
    ForSight Labs, Menlo Park, California, United States
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • Jay M Stewart
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • David Kardatzke
    Genentech, Inc, California, United States
  • Natasha Singh
    Genentech, Inc, California, United States
  • Signe Erickson
    Genentech, Inc, California, United States
  • Footnotes
    Commercial Relationships   Anat Loewenstein, Alcon (R), Alimera (R), Allergan (F), Allergan (R), Bayer (F), Bayer (R), BeyeOnics (R), ForSight Labs (R), ForSight Labs (C), ForSight Labs (I), NotalVision (R), Novartis (F), Novartis (R); Guna Laganovska, None; Neil Bressler, Bayer (F), ForSight Labs (F), Genentech, Inc (F), Novartis (F), Roche (F), Samsung Bioepis (F); Juris Vanags, None; Yair Alster, ForSight Vision4 (I); Eugene De Juan, ForSight Vision4 (I), Genentech, Inc (F), Genentech, Inc (R), Genentech, Inc (P); Jay Stewart, ForSight Vision4 (R), Genentech (R); David Kardatzke, Genentech, Inc (E); Natasha Singh, Genentech, Inc (E); Signe Erickson, ForSight Vision4 (R), Genentech, Inc (R), Genentech, Inc (E)
  • Footnotes
    Support  Genentech, Inc., South San Francisco, CA, provided support for the study and participated in the study design; conducting the study; and data collection, management, and interpretation
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4201. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Anat Loewenstein, Guna Laganovska, Neil M Bressler, Juris Vanags, Yair Alster, Eugene De Juan, Jay M Stewart, David Kardatzke, Natasha Singh, Signe Erickson; Phase 1 Clinical Study of the Port Delivery System with ranibizumab for continuous treatment of neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4201.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
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 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)

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×