Evaluation of a Treat and Extend Regimen of Intravitreal Aflibercept for Macular Edema Secondary to CRVO (CENTERA)

A Multi-center, Single-arm, Interventional Phase 4 Study to Evaluate a Treat and Extend Regimen of Intravitreal Aflibercept for Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion

Central retinal vein occlusion (CRVO) occurs when the main blood vessel that transports blood away from the retina (the very back portion of the eye) becomes blocked, causing the leakage of fluid into the retina and thereby causing a swelling of the macula (the portion of the retina responsible for fine vision). This swelling is called macular edema. When the macula swells with fluid, central vision becomes blurry. The study drug aflibercept has been shown to reduce the amount of fluid and blood leaked into the retina. It can help to stabilize, and in many cases, improve the vision loss related to CRVO. Aflibercept has been approved for the treatment of macular edema secondary to CRVO in the United States (US), European Union (EU), Japan, and other countries.

The study was considered research because, although the study drug was already on the market for macular edema secondary to CRVO, there were no studies available that addressed the questions of what were useful intervals for treating and assessing patients, how did they differ among patients, and how were criteria applied for retreatment. The purpose of this study was to evaluate the effectiveness, treatment interval, and safety of the treatment regimen (pattern for administering treatment) in subjects with macular edema secondary to CRVO. In addition, this study explored new imaging methods for assessing the affected eye.

Study Overview

• Status: Completed
• Conditions: Central Retinal Vein Occlusion
• Intervention / Treatment: Drug: Aflibercept (Eylea, BAY86-5321)

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Parramatta, Australia, 2150
  • New South Wales
    • Albury, New South Wales, Australia, 2640
    • Sydney, New South Wales, Australia, 2000
• Canada
  • Quebec, Canada, G1V 1T6
  • Alberta
    • Calgary, Alberta, Canada, T2H 0C8
  • Ontario
    • Hamilton, Ontario, Canada, L8G 5E4
    • London, Ontario, Canada, N6A 4V2
  • Quebec
    • Boisbriand, Quebec, Canada, J7H 1S6
    • Sherbrooke, Quebec, Canada, J1G 2V4
• Denmark
  • Aalborg, Denmark, 9100
  • Glostrup, Denmark, 2600
• France
  • Bordeaux, France, 33076
  • Dijon Cedex, France, BP 1542-21
  • Lyon, France, 69004
• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
    • Heidelberg, Baden-Württemberg, Germany, 69120
    • Karlsruhe, Baden-Württemberg, Germany, 76133
  • Bayern
    • Augsburg, Bayern, Germany, 86156
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
    • Hannover, Nordrhein-Westfalen, Germany, 30625
    • Köln, Nordrhein-Westfalen, Germany, 50935
    • Münster, Nordrhein-Westfalen, Germany, 48149
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00198
    • Roma, Lazio, Italy, 00133
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20157
  • Marche
    • Ancona, Marche, Italy, 60126
  • Toscana
    • Pisa, Toscana, Italy, 56124
  • Veneto
    • Padova, Veneto, Italy, 35128
• Spain
  • Barcelona, Spain, 08025
  • Barcelona, Spain, 08024
  • Asturias
    • Oviedo, Asturias, Spain, 33012
  • Barcelona
    • Sant Cugat del Vallés, Barcelona, Spain, 08195
    • Viladecans, Barcelona, Spain, 08840
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
  • Colchester, United Kingdom, CO3 3NB
  • Liverpool, United Kingdom, L9 7AL
  • Oxford, United Kingdom, OX3 9DU
  • Tyne And Wear
    • Sunderland, Tyne And Wear, United Kingdom, SR2 9HP
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ

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:

• Center-involved macular edema secondary to CRVO for no longer than 3 months (at the screening visit it should be ensured that the subjects will comply with the criterion of ≤ 3 months since onset of macular edema at their scheduled baseline visit).
• Adult subjects diagnosed with macular edema secondary to CRVO who are scheduled to be treated with IVT aflibercept as per investigator's routine treatment practice with the intent to use a T&E regimen after initial dosing.
• Treatment-naïve subjects for macular edema secondary to CRVO.
• Men and women ≥ 18 years of age.
• Documented BCVA of ETDRS letter score of 73 to 24 letters (Snellen equivalent of 20/40 to 20/320) in the study eye.

Exclusion Criteria:

• Previous PRP or macular laser photocoagulation in the study eye.
• Any prior or concomitant ocular treatment (e.g. anti-VEGF therapy, corticosteroids) in the study eye for macular edema secondary to RVO, except dietary supplements or vitamins prior to inclusion in the study. Intraocular anti-VEGF treatment is permitted for the treatment of diseases of fellow eye except for those that are specifically excluded.
• Prior systemic anti-VEGF or corticosteroid therapy, investigational or approved, within the last 3 months before the first dose in the study.
• Previous use of intraocular corticosteroids in the study eye at any time or use of periocular corticosteroids in the study eye within 12 months prior to Day 1.
• Any active intraocular, extraocular, and periocular inflammation or infection in either eye within 4 weeks of screening.
• Any history of allergy to povidone iodine.
• Known serious allergy to the fluorescein sodium for injection in angiography.
• Presence of any contraindications indicated in the EU commission/locally approved label for IVT aflibercept: hypersensitivity to the active substance IVT aflibercept or to any of the excipients; active or suspected ocular or periocular infection; active severe intraocular inflammation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravitreal (IVT) aflibercept; Participants with macular edema secondary to CRVO were treated with the study drug intravitreal aflibercept	Drug: Aflibercept (Eylea, BAY86-5321); The recommended dose for intravitreal aflibercept was 2 mg equivalent to 50 μL. Study treatment was administered at baseline and at monthly intervals until stabilization of disease. When stability was achieved, the treatment interval could be extended based on visual and anatomic outcomes as judged by the treating investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Participants Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline	Participants who completed the study with a gain of ≥ 15 letters or dropped the study after Week 24 and having a permanent resolution of macular edema and a gain of ≥ 15 letters from baseline with regard to the latest BCVA assessment. The ETDRS chart includes 70 letters in total, more letters read correctly represents a better visual acuity.	Baseline, Week 24 and Week 76
The Proportion of Participants With a Mean Treatment Interval Between Injections of ≥ 8 Weeks	Participants who completed the study with a mean treatment interval between injections of ≥ 8 weeks or dropped out of the study after Week 24 and having a permanent resolution of macular edema	From the last actual visit of the initiation phase to Week 76

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Treatment Interval Between Injections		From baseline to Week 76
The Change in Best Corrected Visual Acuity (BCVA) as Measured by the Early Treatment Diabetic Retinopathy Letter Score (ETDRS) From Baseline	The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity	Baseline and Week 24, 52, and 76
The Change in Central Retinal Thickness (CRT) From Baseline	CRT was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).	Baseline and Week 24, 52 and 76
The Number of Injections Per Participant		From baseline to Week 76
The Proportion of Participants Who Gain ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline	The ETDRS chart includes 70 letters in total. More letters read correctly represents a better visual acuity	Baseline and Week 24, Week 52
The Proportion of Participants With Change in Retinal Non-perfusion (FA/FP) Status From Baseline	The change in retinal non-perfusion status by fundus angiography (FA)/fundus photography (FP)-confirmed ischemic disc area. The status was categorized into: no non-perfusion, <10 ischemic disc area, >=10 ischemic disc area and missing status	Baseline and Week 24, 52 and 76
The Proportion of Participants With Absence of Subretinal Fluid		Baseline, week 24, week 52 and week 76
Incidence and Severity of Ocular Treatment-emergent Adverse Events		Up to 30 days after week 76

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Korobelnik JF, Larsen M, Eter N, Bailey C, Wolf S, Schmelter T, Allmeier H, Chaudhary V. Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend for Macular Edema in Central Retinal Vein Occlusion: the CENTERA Study. Am J Ophthalmol. 2021 Jul;227:106-115. doi: 10.1016/j.ajo.2021.01.027. Epub 2021 Feb 6.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2016
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: June 10, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (Estimate): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: June 19, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Eylea; Aflibercept; Intravitreal; Bayer
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 17514; 2014-003193-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes