INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

Association for Innovation and Biomedical Research on Light and Image Coimbra Portugal

Axon Clinical Research Center Prague Czech Republic

Bayer AG Berlin Germany

Bayer Consumer Care AG Basel Switzerland

Clinical Academic Center of Coimbra Coimbra Portugal

Coimbra Institute for Clinical and Biomedical Research Faculty of Medicine University of Coimbra Coimbra Portugal

Department of Ophthalmology and Vision Sciences University of Toronto Toronto ON Canada

Department of Ophthalmology Croix Rousse Teaching Hospital Hospices Civils de Lyon Lyon France

Department of Ophthalmology Hospital Universitario de Bellvitge Barcelona Spain

Department of Ophthalmology Semmelweis University Budapest Hungary

Department of Ophthalmology University Hospital Padua Italy

Department of Ophthalmology University of Barcelona Barcelona Spain

Ophthalmology Department Centro Hospitalar e Universitário de Coimbra Coimbra Portugal

The John and Liz Tory Eye Centre Sunnybrook Health Sciences Centre Toronto ON Canada

UMR CNRS 5510 Matéis Villeurbanne Université Claude Bernard Lyon 1 University of Lyon Lyon France

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ClinicalTrials.gov
NCT02540954