A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration
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Date
2023-06
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Abstract
Purpose: Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti–VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti–VEGF-A inhibitor ranibizumab. Design: Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial. Participants: Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States. Methods: Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab. Main Outcome Measures: The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT. Results: Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs. +10.8 ± 11.52 letters; P = 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P = 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm. Conclusions: Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082). Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Description
Funding Information: The trial was wholly funded by Opthea Ltd (Victoria, Australia). Opthea designed and interpreted the trial data, with input from consultant clinical advisors (T.L.J., J.S., P.U.D., C.C.W., D.S.B.). Opthea partnered with 2 contract research organizations during the conduct of the study, with Pharmaceutical Product Development LLC (Wilmington, DE) to execute the study, and with International Drug Development Institute (Louvain-la-Neuve, Belgium) to undertake the data management and biostatistical analysis. Opthea (and the coauthors) provided critical review of the first draft manuscript (prepared by T.L.J.). Publisher Copyright: © 2023 American Academy of Ophthalmology
Keywords
Anti–VEGF-C and D inhibitor, Intravitreal injection, Neovascular age-related macular degeneration, OPT-302, Randomized controlled trial, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Ophthalmology
Citation
Jackson, T L, Slakter, J, Buyse, M, Wang, K, Opthea Study Group Investigators & Laganovska, G 2023, 'A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration', Ophthalmology, vol. 130, no. 6, pp. 588-597. https://doi.org/10.1016/j.ophtha.2023.02.001