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

Wet Age-Related Macular Degeneration Clinical Trial

— TIDE AMD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02257632
• Other study ID #: CRFB002ADE27
• Status: Completed
• Phase: Phase 4
• Start date: April 8, 2015
• Est. completion date: June 8, 2017

Study information

• Verified date: January 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 8, 2017
• Est. primary completion date: March 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Wet Age-Related Macular Degeneration

Intervention

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

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Osnabrück
Germany	Novartis Investigative Site	Regensburg

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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