A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration
Copyright © 2023 American Academy of Ophthalmology. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
Ophthalmology - 130(2023), 6 vom: 20. Juni, Seite 588-597 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jackson, Timothy L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.05.2023 Date Revised 24.05.2023 published: Print-Electronic ClinicalTrials.gov: NCT03345082 Citation Status MEDLINE |
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| doi: |
10.1016/j.ophtha.2023.02.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352640316 |
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| 100 | 1 | |a Jackson, Timothy L |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 22.05.2023 | ||
| 500 | |a Date Revised 24.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03345082 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 American Academy of Ophthalmology. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a DESIGN: Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial | ||
| 520 | |a PARTICIPANTS: Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Anti–VEGF-C and D inhibitor | |
| 650 | 4 | |a Intravitreal injection | |
| 650 | 4 | |a Neovascular age-related macular degeneration | |
| 650 | 4 | |a OPT-302 | |
| 650 | 4 | |a Randomized controlled trial | |
| 650 | 7 | |a Ranibizumab |2 NLM | |
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| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 650 | 7 | |a Angiogenesis Inhibitors |2 NLM | |
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