Macular DegenerationPhase 3NCT02540954
Efficacy and Safety of Two Different Aflibercept Regimens in Subjects With Neovascular Age-related Macular Degeneration (nAMD)
A Phase 3 study testing Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) in people with Macular Degeneration, run by Bayer at 71 sites in 14 countries.
Trial summary
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) Read more about this study
- Who is it for?
- Ages 51 years and older
- Conditions the study is for
- Macular Degeneration
- What is being tested?
- Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 336 participants
- Where
- 71 sitesin 14 countries
- Study dates
- 29 Sep 2015to 4 Jun 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 51 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
- 50% or more of the total lesion area, or
- if the blood was under the fovea, and
- the blood under the fovea was 1 or more disc areas in size in the study eye.
Show all 10Show fewer
- 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.
Trial locations and contacts
71 sites in 14 countries.
71 sites in 14 countries
United Kingdom15 sites
Study site
Colchester, CO3 3NB
Study site
Great Yarmouth, Norfolk, NR31 6LA
Study site
Guildford, Surrey, GU2 7XX
Study site
Hull, York, HU3 2JZ
Study site
Liverpool, Merseyside, L7 8XP
Study site
London, NW1 5QH
Study site
London, SE5 9RS
Study site
Manchester, M13 9WL
Study site
Middlesbrough, North Yorkshire, TS4 3BW
Study site
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
Study site
Pont-y-clun, Rhondda, Cynon, Taff, CF72 8XR
Study site
Rugby, Warwickshire, CV22 5PX
Study site
Southampton, Hampshire, SO16 6YD
Study site
Sunderland, Tyne and Wear, SR2 9HP
Study site
Wakefield, West Yorkshire, WF1 4DG
Italy12 sites
Study site
Brescia, Lombardy, 25015
Study site
Catania, Sicily, 95123
Study site
Genoa, Liguria, 16132
Study site
Milan, Lombardy, 20122
Study site
Milan, Lombardy, 20132
Study site
Milan, Lombardy, 20157
Study site
Parma, 43126
Study site
Pisa, Tuscany, 56124
Study site
Rome, Lazio, 00133
Study site
Rome, Lazio, 00198
Study site
Turin, Piedmont, 10122
Study site
Verona, Veneto, 37134
Germany10 sites
Study site
Berlin, 10713
Study site
Berlin, 12203
Study site
Darmstadt, Hesse, 64297
Study site
Düsseldorf, North Rhine-Westphalia, 40225
Study site
Frankfurt am Main, Hesse, 60596
Study site
Göttingen, Lower Saxony, 37075
Study site
Hamburg, 20251
Study site
Leipzig, Saxony, 04103
Study site
Marburg, Hesse, 35037
Study site
Würzburg, Bavaria, 97080
France6 sites
Study site
Bordeaux, 33000
Study site
Dijon, BP 1542-21
Study site
Lyon, 69317
Study site
Nice, 06006
Study site
Paris, Cedex 12, 75557
Study site
Paris, 75010
Czechia5 sites
Study site
Hradec Králové, 500 05
Study site
Pilsen, 304 60
Study site
Prague, 100 34
Study site
Prague, 12808
Study site
Prague, 150 00
Portugal4 sites
Study site
Coimbra, 3000-548
Study site
Leiria, 2410-197
Study site
Lisbon, 1649-035
Study site
Porto, 4200-319
Hungary3 sites
Study site
Budapest, 1085
Study site
Debrecen, 4032
Study site
Pécs, 7621
Slovakia3 sites
Study site
Bratislava, 826 06
Study site
Bratislava, 851 07
Study site
Nitra, 949 01
Spain3 sites
Study site
Barcelona, 08036
Study site
L'Hospitalet de Llobregat, Barcelona, 08907
Study site
Valencia, 46014
Canada2 sites
Clinique medicale de l'oeil de l'Estrie
Sherbrooke, Quebec, J1J 2B8
Study site
Toronto, Ontario, M4N 3M5
About this study
Official title: 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)
Read the 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.
- Conditions
- Macular Degeneration
- Being tested
- Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
- Keywords
- Age-related macular degeneration (AMD), Eylea treatment, Treat and Extend, Intravitreal
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)Drug
A dose of 2 mg aflibercept injected intravitreally
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept extended dosing | Experimental | 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). Receives: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) |
| Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks) | Active comparator | 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. Receives: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to Week 52
Secondary outcomes (7)
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.
Measured: At week 52
Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye
Measured: 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).
Measured: 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).
Measured: From baseline to week 52
Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye
Measured: 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.
Measured: From baseline to week 52
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study start29 Sep 2015
- Primary completion24 Dec 2019
- Study completion4 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Macular DegenerationStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 336 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02540954
- Sponsor's protocol ID
- 16598
- Other IDs
- 2013-000120-33
- Status last verified
- Jun 2021
- First submitted
- 2 Sep 2015
- Last updated
- 11 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
Kodjikian L, Arias Barquet L, Papp A, Kertes PJ, Midena E, Ernest J, Silva R, Schmelter T, Niesen T, Leal S. Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing. Adv Ther. 2024 Mar;41(3):1010-1024. doi: 10.1007/s12325-023-02719-3. Epub 2024 Jan 6.
PubMed 38183525
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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).
- ClinicalTrials.gov ID
- NCT02540954
- Acronym / sponsor ID
- 16598
- Conditions
- Macular Degeneration
- Keywords
- Age-related macular degeneration (AMD), Eylea treatment, Treat and Extend, Intravitreal
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 336 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 29 Sep 2015 (actual)
- Primary completion
- 24 Dec 2019 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 4 Sep 2015 (estimated)
- Results
- Posted 8 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aflibercept extended dosing | Experimental | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)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). |
| Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks) | Active comparator | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)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. |
Who may qualify
- Ages
- 51 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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):
- Men and women >= 51 years of age
- The subject's history of aflibercept treatment meets ALL of the following:
Key exclusion criteria (10 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)A dose of 2 mg aflibercept injected intravitreally | Drug | Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks), Aflibercept extended dosing |
Primary outcome
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye
Time frame: From baseline to Week 52
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.
7 secondary outcomes
Percentage of Participants Maintaining Vision in the Study Eye
Time frame: At week 52
Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye
Time frame: At week 52
Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye
Time frame: From baseline to week 52
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye
Time frame: From baseline to week 52
Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye
Time frame: At week 52
Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire
Time frame: From baseline to week 52
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38183525Kodjikian L, Arias Barquet L, Papp A, Kertes PJ, Midena E, Ernest J, Silva R, Schmelter T, Niesen T, Leal S. Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing. Adv Ther. 2024 Mar;41(3):1010-1024. doi: 10.1007/s12325-023-02719-3. Epub 2024 Jan 6.
- Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
71 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) in people with Macular Degeneration, run by Bayer at 71 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United Kingdom, Italy, Germany, France, Czechia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye (time frame: From baseline to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02540954, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2021.