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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Visual Impairment Due to Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab; Drug: Aflibercept

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Chemnitz, Germany, 09113
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Monthly intravitreal injections of 0.5 mg ranibizumab	Drug: Ranibizumab; 0.5 mg intravitreal injections; Other Names: Lucentis
Experimental: Group 2; Three monthly intravitreal injections of 2 mg aflibercept followed by three monthly intravitreal injections of 0.5 mg ranibizumab	Drug: Ranibizumab; 0.5 mg intravitreal injections; Other Names: Lucentis; Drug: Aflibercept; 2 mg intravitreal injections; Other Names: Eylea

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceutical, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimate): October 7, 2014

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Sensation Disorders; Macular Edema; Edema; Vision, Low; Vision Disorders; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Aflibercept
• Other Study ID Numbers: CRFB002DDE25