Phase 1 Study of OPT-302 Inhibition of Vascular Endothelial Growth Factors C and D for Neovascular Age-Related Macular Degeneration.
Ophthalmol Retina
; 4(3): 250-263, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31924544
ABSTRACT
PURPOSE:
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).DESIGN:
Open-label, dose escalation followed by a randomized dose expansion.PARTICIPANTS:
Fifty-one patients with nAMD who were either treatment naïve (n = 25) or previously were treated with anti-VEGF A therapy (n = 26).METHODS:
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 (31) 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. MAIN OUTCOMEMEASURES:
Safety and tolerability, OPT-302 pharmacokinetics and immunogenicity, effects on best-corrected visual acuity (BCVA), and anatomic changes.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Angiogênese
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Fator C de Crescimento do Endotélio Vascular
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Fator D de Crescimento do Endotélio Vascular
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Degeneração Macular Exsudativa
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Ophthalmol Retina
Ano de publicação:
2020
Tipo de documento:
Article