Phase 1 Study of OPT-302 Inhibition of Vascular Endothelial Growth Factors C and D for Neovascular Age-Related Macular Degeneration
OPT-302 is a novel inhibitor of vascular endothelial growth factor (VEGF)-C and VEGF-D. A phase 1 trial assessed the safety of intravitreal OPT-302 as monotherapy or combined with ranibizumab (Lucentis; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration...
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Veröffentlicht in: | Ophthalmology retina 2020-03, Vol.4 (3), p.250-263 |
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Zusammenfassung: | OPT-302 is a novel inhibitor of vascular endothelial growth factor (VEGF)-C and VEGF-D. A phase 1 trial assessed the safety of intravitreal OPT-302 as monotherapy or combined with ranibizumab (Lucentis; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD).
Open-label, dose escalation followed by a randomized dose expansion.
Fifty-one patients with nAMD who were either treatment naïve (n = 25) or previously were treated with anti-VEGF A therapy (n = 26).
In the dose escalation, groups of 5 patients in 4 cohorts received ascending doses of OPT-302 (0.3 mg, 1 mg, or 2 mg) in combination with ranibizumab (0.5 mg), or as monotherapy (2 mg). In the dose expansion, 31 patients were randomized (3:1) to OPT-302 (2 mg) in combination with ranibizumab (n = 23) or as monotherapy (n = 8). Participants received three intravitreal treatments of OPT-302 once every 4 weeks either with or without ranibizumab.
Safety and tolerability, OPT-302 pharmacokinetics and immunogenicity, effects on best-corrected visual acuity (BCVA), and anatomic changes.
Intravitreal OPT-302 with or without ranibizumab was well tolerated with low systemic exposure, no dose-limiting toxicities and no immunogenicity. In patients receiving OPT-302 monotherapy, 7 of 13 (54%) did not require rescue anti-VEGF-A therapy and the mean change in BCVA from baseline to week 12 was +5.6 letters (range, 0–18 letters). Mean BCVA gains from baseline to week 12 following combination OPT-302 with ranibizumab were +10.8 letters (95% confidence interval [CI], 4–17; n = 18) in treatment-naïve patients and +4.9 letters (95% CI, 3–7; n = 19) in previously treated patients, respectively. Corresponding reductions in mean central subfield thickness at week 12 in both groups were –119 μm (95% CI, –176 to –62 μm) and –54 μm (95% CI, –82 to –26 μm), respectively, whilst 50% of treatment-naïve patients also showed no detectable choroidal neovascularization at week 12 on fluorescein angiography.
Intravitreal OPT-302 inhibition of VEGF-C and -D was well tolerated, and OPT-302 combination therapy may overcome an escape mechanism to VEGF-A suppression in the management of nAMD. |
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ISSN: | 2468-6530 2468-6530 |
DOI: | 10.1016/j.oret.2019.10.008 |