Efficacy and Safety of Two Different Aflibercept Regimens in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of 2 mg Aflibercept Administered by Intravitreal Injections Using Two Different Treatment Regimens to Subjects With Neovascular Age-related Macular Degeneration (nAMD).

To compare the efficacy of 2 mg aflibercept administered by two different intravitreal (IVT) treatment regimens to subjects with neovascular age-related macular degeneration (nAMD)

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Detailed Description

330 Patients who have completed at least one year of treatment with aflibercept will be randomized to two different aflibercept regimens and followed for 76 weeks.

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
  • Wien, Austria, 1140
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
  • Quebec
    • Sherbrooke, Quebec, Canada, J1J 2B8
      • Clinique medicale de l'oeil de l'Estrie
• Czechia
  • Hradec Kralove, Czechia, 500 05
  • Plzen, Czechia, 304 60
  • Praha 10, Czechia, 100 34
  • Praha 2, Czechia, 12808
  • Praha 5, Czechia, 150 00
• France
  • Bordeaux, France, 33000
  • Dijon Cedex, France, BP 1542-21
  • Lyon Cedex 04, France, 69317
  • Nice Cedex, France, 06006
  • Paris, France, 75010
  • Cedex 12
    • Paris, Cedex 12, France, 75557
• Germany
  • Berlin, Germany, 10713
  • Berlin, Germany, 12203
  • Hamburg, Germany, 20251
  • Bayern
    • Würzburg, Bayern, Germany, 97080
  • Hessen
    • Darmstadt, Hessen, Germany, 64297
    • Frankfurt, Hessen, Germany, 60596
    • Marburg, Hessen, Germany, 35037
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
• Hungary
  • Budapest, Hungary, 1085
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7621
• Italy
  • Parma, Italy, 43126
  • Lazio
    • Roma, Lazio, Italy, 00198
    • Roma, Lazio, Italy, 00133
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Brescia, Lombardia, Italy, 25015
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20157
    • Milano, Lombardia, Italy, 20122
  • Piemonte
    • Torino, Piemonte, Italy, 10122
  • Sicilia
    • Catania, Sicilia, Italy, 95123
  • Toscana
    • Pisa, Toscana, Italy, 56124
  • Veneto
    • Verona, Veneto, Italy, 37134
• Lithuania
  • Kaunas, Lithuania, LT-50009
  • Vilnius, Lithuania, LT-08661
• Poland
  • Gdansk, Poland, 80-809
  • Olsztyn, Poland, 10-424
• Portugal
  • Coimbra, Portugal, 3000-548
  • Leiria, Portugal, 2410-197
  • Lisboa, Portugal, 1649-035
  • Porto, Portugal, 4200-319
• Slovakia
  • Bratislava, Slovakia, 826 06
  • Bratislava, Slovakia, 851 07
  • Nitra, Slovakia, 949 01
• Spain
  • Barcelona, Spain, 08036
  • Valencia, Spain, 46014
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
• Switzerland
  • Bern, Switzerland
  • Genève, Switzerland, 1204
• United Kingdom
  • Colchester, United Kingdom, CO3 3NB
  • London, United Kingdom, SE5 9RS
  • London, United Kingdom, NW1 5QH
  • Manchester, United Kingdom, M13 9WL
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
  • Norfolk
    • Great Yarmouth, Norfolk, United Kingdom, NR31 6LA
  • North Yorkshire
    • Middlesborough, North Yorkshire, United Kingdom, TS4 3BW
  • Rhondda, Cynon, Taff
    • Pontyclun, Rhondda, Cynon, Taff, United Kingdom, CF72 8XR
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
    • Sunderland, Tyne And Wear, United Kingdom, SR2 9HP
  • Warwickshire
    • Rugby, Warwickshire, United Kingdom, CV22 5PX
  • West Yorkshire
    • Wakefield, West Yorkshire, United Kingdom, WF1 4DG
  • York
    • Hull, York, United Kingdom, HU3 2JZ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The following criteria must have been met at the initial start of aflibercept treatment (i.e. start of aflibercept treatment at least 1 year before this study):

  • Subject had primary subfoveal choroidal neovascularization (CNV) lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea, as evidenced by fluorescein angiography/photography (FA/FP) of the study eye within 3 weeks before the initiation of aflibercept treatment.
  • The area of CNV occupied at least 50% of the total lesion within 3 weeks before the initiation of aflibercept treatment.
  • Documented best-corrected visual acuity (BCVA) was 20/40 to 20/320 (letter score of 73 to 25) in the study eye at the initiation of treatment.
• Men and women >= 51 years of age

• The subject's history of aflibercept treatment meets ALL of the following:

  • Treatment in the study eye was initiated with three monthly (-1 week/+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed
  • Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks

Exclusion Criteria:

- Any prior or concomitant therapy with an investigational or approved agent to treat neovascular AMD in the study eye other than aflibercept.

• Total lesion size > 12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by fluorescein angiography (FA) in the study eye

• Subretinal hemorrhage that was:

  1. 50% or more of the total lesion area, or
  2. if the blood was under the fovea, and
  3. the blood under the fovea was 1 or more disc areas in size in the study eye.
• Scar or fibrosis making up more than 50% of the total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• Causes of CNV other than AMD in the study eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept extended dosing; Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed).	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); A dose of 2 mg aflibercept injected intravitreally
Active Comparator: Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks); Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed.	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); A dose of 2 mg aflibercept injected intravitreally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye	Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function.	From baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Maintaining Vision in the Study Eye	A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.	At week 52
Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye		At week 52
Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye	Retinal characteristic was evaluated using Optical coherence tomography (OCT).	From baseline to week 52
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye	Choroidal neovascularization measured by optical coherence tomography (OCT).	From baseline to week 52
Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye		At week 52
Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire	National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst.	From baseline to week 52
Number of Participants With Treatment-emergent Adverse Events (TEAE)		Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

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): September 29, 2015
• Primary Completion (Actual): December 24, 2019
• Study Completion (Actual): June 4, 2020

Study Registration Dates

• First Submitted: September 2, 2015
• First Submitted That Met QC Criteria: September 2, 2015
• First Posted (Estimate): September 4, 2015

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Age-related macular degeneration (AMD); Intravitreal; Treat and Extend; Eylea treatment
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 16598; 2013-000120-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

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