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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Participant)
  • Study Primary Completion Date: March 20, 2017

Detailed Description

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.

Interventions

  • Drug: Ranibizumab 0.5 mg
    • Administered as an intravitreal injection
  • Drug: Aflibercept 2 mg
    • Administered as an intravitreal injection

Arms, Groups and Cohorts

  • Experimental: Group 1
    • 6 monthly intravitreal injections of 0.5 mg ranibizumab
  • Experimental: Group 2
    • 3 monthly intravitreal injections of 2 mg aflibercept followed by 3 monthly intravitreal injections of 0.5 mg ranibizumab

Clinical Trial Outcome Measures

Primary Measures

  • Standardized Area Under the Curve (AUC) for VEGF A Levels by SIMOA (Quanterix’s Single Molecule Array) Method for the Comparative Phase
    • Time Frame: Baseline up to Week 12 visit (Days 1, 2, 8, 15, 29, 43, 57, 71, 85)
    • 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.

Secondary Measures

  • Systemic VEGF-A Protein Levels From Study Week 12 to 24
    • Time Frame: From study week 12 to 24 (Days 85, 99, 113, 127, 141, 155, 169)
    • 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)
  • Systemic VEGF-A Levels From Study Week 12 to 24 (Change From Baseline)
    • Time Frame: From study week 12 to 24
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

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