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A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration.

Publication ,  Journal Article
Jackson, TL; Slakter, J; Buyse, M; Wang, K; Dugel, PU; Wykoff, CC; Boyer, DS; Gerometta, M; Baldwin, ME; Price, CF; Opthea Study Group Investigators
Published in: Ophthalmology
June 2023

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.

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Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

June 2023

Volume

130

Issue

6

Start / End Page

588 / 597

Location

United States

Related Subject Headings

  • Wet Macular Degeneration
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Ranibizumab
  • Ophthalmology & Optometry
  • Intravitreal Injections
  • Humans
  • Antibodies, Monoclonal, Humanized
  • Angiogenesis Inhibitors
 

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Jackson, T. L., Slakter, J., Buyse, M., Wang, K., Dugel, P. U., Wykoff, C. C., … Opthea Study Group Investigators. (2023). A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration. Ophthalmology, 130(6), 588–597. https://doi.org/10.1016/j.ophtha.2023.02.001
Jackson, Timothy L., Jason Slakter, Marc Buyse, Kun Wang, Pravin U. Dugel, Charles C. Wykoff, David S. Boyer, et al. “A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration.Ophthalmology 130, no. 6 (June 2023): 588–97. https://doi.org/10.1016/j.ophtha.2023.02.001.
Jackson TL, Slakter J, Buyse M, Wang K, Dugel PU, Wykoff CC, et al. A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2023 Jun;130(6):588–97.
Jackson, Timothy L., et al. “A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration.Ophthalmology, vol. 130, no. 6, June 2023, pp. 588–97. Pubmed, doi:10.1016/j.ophtha.2023.02.001.
Jackson TL, Slakter J, Buyse M, Wang K, Dugel PU, Wykoff CC, Boyer DS, Gerometta M, Baldwin ME, Price CF, Opthea Study Group Investigators. A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2023 Jun;130(6):588–597.
Journal cover image

Published In

Ophthalmology

DOI

EISSN

1549-4713

Publication Date

June 2023

Volume

130

Issue

6

Start / End Page

588 / 597

Location

United States

Related Subject Headings

  • Wet Macular Degeneration
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Ranibizumab
  • Ophthalmology & Optometry
  • Intravitreal Injections
  • Humans
  • Antibodies, Monoclonal, Humanized
  • Angiogenesis Inhibitors