Effect of Aflibercept (Eylea®) in the Management of Bevacizumab (Avastin®) Resistant Diabetic Macular Edema — Eylea  

Diabetic Macular Edema Clinical Trial

Official title: Effect of Aflibercept (Eylea®) in the Management of Bevacizumab (Avastin®) Resistant Diabetic Macular Edema

Status Recruiting

Clinical Trial Summary

Multicenter randomized trials have demonstrated the safety and efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of diabetic macular edema. The results are generally good in the short term, with approximately 75% of patients maintaining or improving vision after initiation of treatment. Despite this favorable outcome, the observation of persistent fluid is not infrequent during treatment, even in patients undergoing monthly treatment sessions. Persistent fluid was observed on optical coherence tomography (OCT) in 70.9% of patients receiving bevacizumab monthly and in 79% of those receiving bevacizumab as needed at the end of the first year in the Comparison of diabetic macular edema. Treatment Trials. It is possible that resolution of this fluid, especially when it is centrally located (i.e., foveal), might result in better visual outcomes.

A drug with higher VEGF-binding affinity may help patients with persistent fluid despite treatment with bevacizumab. Aflibercept is a new intravitreal VEGF antagonist approved on 28 November 2014 by the Health Canada for the treatment of diabetic macular edema.

In contrast to the antibody-based VEGF binding strategy used by bevacizumab, aflibercept incorporates the second binding domain of the VEGFR-1 receptor and the third domain of the VEGFR-2 receptor. By fusing these extracellular protein sequences to the Fc segment of a human IgG backbone, developers have created a chimeric protein with a very high VEGF binding affinity. Aflibercept binds all isomers of the VEGF-A family like bevacizumab, but it also binds VEGF-B and placental growth factors 1 and 2,1,2 which have been both implicated in the pathogenesis of diabetic retinopathy and of age-related macular degeneration. In addition, because of the increased trough binding activity and the stronger binding affinity, aflibercept should be efficacious in neutralizing VEGF more effectively and for longer duration.

Clinical Trial Description

In this study patients recruitment, clinical care and follow-up will be conducted by:

Dr Flavio Rezende: Principal-Investigator and Dr Radwan Ajlan: Co-Investigator.

1. Purpose: To evaluate the visual acuity outcomes and macular changes at 6 and 12 months of intravitreal aflibercept (2.0 mg) in eyes with persistent center involved diabetic macular edema despite intravitreal bevacizumab therapy.

2. Overall Goal of Study: The goal of this study is to evaluate the effect of aflibercept on macular edema in patients with diabetic macular edema resistant to bevacizumab.

3. Specific objectives: To evaluate the visual acuity outcomes and macular changes after 6 and 12 months of intravitreal aflibercept (2.0 mg) in eyes with persistent foveal fluid secondary to diabetic macular edema despite previous optimum gold standard therapy with intravitreal bevacizumab. More specifically, to assess:

• Mean change in central subfield thickness (CST) from baseline, 6 month after switching to aflibercept.

• Mean change in CST from baseline, 12 months after switching to aflibercept.

• Mean change in best corrected visual acuity (BCVA) from baseline, 6 months after switching to aflibercept.

• Mean change in BCVA from baseline, 12 months after switching to aflibercept

4. Study Design: Phase 4 open label clinical trial. Intravitreal injection of 0.05 mL (2mg) of aflibercept will be injected. The intravitreal between the first 5 treatments sessions is 4 weeks, and the intravitreal for the following treatment sessions up to week 52 is 8 weeks.

5. Subjects: 40 patients seen in the retinal clinic of the Hospital Maisonneuve-Rosemont with foveal fluid secondary to diabetic macular edema despite previous optimum gold standard therapy with intravitreal bevacizumab will be assessed for eligibility. ;

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

• NCT number: NCT02924987
• Study type: Interventional
• Source: Maisonneuve-Rosemont Hospital
• Contact: Manon Lambert
• Phone: 514-252-3400
• Email: mlambert.hmr@ssss.gouv.qc.ca
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2016
• Completion date: November 2017