Systemic VEGF Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of the study is to compare the effect of intravitreal injections of ranibizumab and aflibercept on systemic VEGF protein levels in DME patients in a detailed time course.

Official Title
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A Randomized, Single-blinded, Multicenter, Phase IV Study to Compare Systemic VEGF Protein Dynamics Following Monthly Intravitreal Injections of 0.5 mg Ranibizumab Versus 2 mg Aflibercept Until Study Week 12 in Patients With Visual Impairment Due to Diabetic Macular Edema

Conditions
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Visual Impairment Due to Diabetic Macular Edema

Intervention / Treatment
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* Drug: Ranibizumab
* Drug: Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or Type 2 diabetes mellitus Visual impairment predominantly due to DME. Exclusion Criteria: Stroke or myocardial infarction less than 3 months prior to screening. Presence of uncontrolled systolic blood pressure or diastolic blood pressure Renal failure requiring dialysis or renal transplant or renal insufficiency Untreated diabetes mellitus Use of any systemic anti-VEGF drugs Use of systemic or inhaled corticosteroids for at least 30 consecutive days within 3 months prior to screening. Women who are pregnant or breast feeding or who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception For either eye: Any active periocular or ocular infection or inflammation Uncontrolled glaucoma Neovascularization of the iris or neovascular glaucoma History of treatment with any anti-angiogenic drugs For study eye: Atrophy or fibrosis involving the center of the fovea at the time of screening or baseline. Cataract (if causing significant visual impairment), planned cataract surgery during the study period, vitrectomy, aphakia, glaucoma surgery, severe vitreous hemorrhage, rhegmatogenous retinal detachment, proliferative retinopathy or choroidal neovascularization or macular edema of any other cause than DME Irreversible structural damage within 0.5 disc diameter of the center of the macula Panretinal laser photocoagulation within 6 months prior to randomization. Focal/grid laser photocoagulation within 3 months prior to randomization. Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months following Topical ocular corticosteroids administered for at least 30 consecutive days within 3 months prior to screening. Application of intravitreal corticosteroids in vitreous within 6 months prior to screening. Prior application of fluocinolonacetonid releasing implant in vitreous within 36 months prior to screening. For fellow eye - Retinal or choroidal neovascularization or macula edema of any cause Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Monthly intravitreal injections of 0.5 mg ranibizumab | Drug: Ranibizumab<br>* 0.5 mg intravitreal injections<br>* Other names: Lucentis;|
| Experimental: Group 2<br>Three monthly intravitreal injections of 2 mg aflibercept followed by three monthly intravitreal injections of 0.5 mg ranibizumab | Drug: Ranibizumab<br>* 0.5 mg intravitreal injections<br>* Other names: Lucentis;Drug: Aflibercept<br>* 2 mg intravitreal injections<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic VEGF-A protein levels | Systemic VEGF-A protein levels following monthly intravitreal injections of 0.5 mg ranibizumab versus 2 mg aflibercept (Area under the curve) | From baseline to study week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic VEGF-A protein levels | Systemic VEGF-A protein levels in patients switching from monthly 2 mg aflibercept injections to monthly 0.5 mg ranibizumab compared to patients treated with 0.5 mg ranibizumab from baseline | From study week 12 to 24 | 
| Systemic VEGF-A levels | Adjustment of systemic VEGF-A levels of patients switching from aflibercept to ranibizumab to levels comparable to baseline or to levels comparable as in patients treated from baseline with ranibizumab | From study week 12 to 24 |