Systemic Vascular Endothelial Growth Factor (VEGF) Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Neovascular Age-related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of the study was to compare the effect of intravitreal injections of ranibizumab and aflibercept on systemic VEGF protein levels in treatment naïve wet neovascular Age-related Macular Degeneration (wAMD) patients in a detailed time course.

Detailed Description
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A planned study visit schedule was established at the time of baseline visit (day 1) for all patients. Study assessments for patients were performed at screening visit, baseline (day 1), day 2, day 8 (± 1 day to allow for flexibility in scheduling) and as of day 15 through to day 169 at biweekly visits.

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 Neovascular (Wet) Age-related Macular Degeneration

Conditions
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Wet Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab 0.5 mg
* Drug: Aflibercept 2 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visual impairment predominantly due to neovascular AMD. Active, newly diagnosed, untreated, angiographically documented, CNV lesion (i.e. leakage on fluorescein angiography plus intraretinal, subretinal or sub-RPE fluid on OCT) secondary to neovascular AMD in line with SmPC of ranibizumab and aflibercept Exclusion Criteria: Stroke or myocardial infarction less than 3 months prior to screening. Presence of uncontrolled systolic blood pressure or diastolic blood pressure Type 1 or Type 2 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 of any other cause than wAMD Irreversible structural damage within 0.5 disc diameter of the center of the macula Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months following baseline. Use of intravitreal or topical ocular corticosteroids administered for at least 30 consecutive days within 3 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>6 monthly intravitreal injections of 0.5 mg ranibizumab | Drug: Ranibizumab 0.5 mg<br>* Administered as an intravitreal injection<br>* Other names: Lucentis;|
| Experimental: Group 2<br>3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab | Drug: Ranibizumab 0.5 mg<br>* Administered as an intravitreal injection<br>* Other names: Lucentis;Drug: Aflibercept 2 mg<br>* Administered as an intravitreal injection<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix's Single Molecule Array) Method for the Comparative Phase | The AUC was calculated using the trapezoidal rule, where all available measurement between Day 1 and Week 12 were used. The AUC was standardized by dividing the calculated value by the number of days from first to last measurement. | Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic VEGF-A Protein Levels From Study Week 12 to 24 | 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 monthly 0.5 mg ranibizumab from baseline (standardized area under the curve) | From study week 12 to 24 (Days 85, 99, 113, 127, 141, 155, 169) | 
| Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline) | 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 |