NCT02540954

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

Completed Phase 3 Results posted Last updated 11 June 2021

What this trial tests

Phase 3 trial testing Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) in Macular Degeneration in 336 participants. Completed in 4 June 2020.

Timeline

29 September 2015

Primary endpoint
24 December 2019

4 June 2020

Quick facts

Lead sponsor	Bayer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	336
Start date	29 September 2015
Primary completion	24 December 2019
Estimated completion	4 June 2020
Sites	71 locations across France, Italy, Slovakia, Austria, United Kingdom, Germany, Hungary, Poland

Drugs / interventions tested

• Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) — full drug profile →

Conditions studied

• Macular Degeneration — all drugs for Macular Degeneration →

Sponsor

Bayer — full company profile →

Who can join

51 and older, any sex, with Macular Degeneration. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye Primary · 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.

Group	Value	95% CI
Aflibercept Extended Dosing	-0.3	± 7.5
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	-0.5	± 8.4

Percentage of Participants Maintaining Vision in the Study Eye Secondary · At week 52

A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline.

Group	Value	95% CI
Aflibercept Extended Dosing	95.2
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	94.0

Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye Secondary · At week 52

Group	Value	95% CI
Aflibercept Extended Dosing	24.2
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	21.0

Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye Secondary · From baseline to week 52

Retinal characteristic was evaluated using Optical coherence tomography (OCT).

Group	Value	95% CI
Aflibercept Extended Dosing	-24.4	± 55.2
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	-33.4	± 47.1

Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye Secondary · From baseline to week 52

Choroidal neovascularization measured by optical coherence tomography (OCT).

Group	Value	95% CI
Aflibercept Extended Dosing	0.274	± 2.723
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	0.204	± 2.813

Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye Secondary · At week 52

Group	Value	95% CI
Aflibercept Extended Dosing	0
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	0.6

Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire Secondary · From baseline to week 52

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.

Group	Value	95% CI
Aflibercept Extended Dosing	0.186	± 9.601
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	-1.694	± 10.328

Number of Participants With Treatment-emergent Adverse Events (TEAE) Secondary · 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

Any TEAE

Group	Value	95% CI
Aflibercept Extended Dosing	130
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	124

Any serious TEAE

Group	Value	95% CI
Aflibercept Extended Dosing	26
Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)	23

Adverse events — posted to ClinicalTrials.gov

Time frame: From after the first application of aflibercept in the study to 30 days after the last dose of study drug over approximately 1.5 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Aflibercept Extended Dosing

Serious: 26/167 (16%)

Deaths: 0/167

Aflibercept 2Q8 (2 mg Aflibercept Administered Every 8 Weeks)

Serious: 23/168 (14%)

Deaths: 3/168

Serious adverse events (58 terms)

Reaction	System	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Afli…
Myocardial infarction	Cardiac disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Atrial fibrillation	Cardiac disorders	—	—
Retinal haemorrhage	Eye disorders	—	—
Pneumonia	Infections and infestations	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Atrial flutter	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Coronary artery stenosis	Cardiac disorders	—	—
Retinal tear	Eye disorders	—	—
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	—	—
Intestinal perforation	Gastrointestinal disorders	—	—
Oedematous pancreatitis	Gastrointestinal disorders	—	—
Gastrointestinal vascular malformation haemorrhagic	Gastrointestinal disorders	—	—
General physical health deterioration	General disorders	—	—
Cholecystitis	Hepatobiliary disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Appendicitis	Infections and infestations	—	—
Endophthalmitis	Infections and infestations	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Aflibercept Extended Dosing	Aflibercept 2Q8 (2 mg Afli…
Cataract	Eye disorders	—	—
Visual acuity reduced	Eye disorders	—	—
Subretinal fluid	Eye disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Intraocular pressure increased	Investigations	—	—
Neovascular age-related macular degeneration	Eye disorders	—	—
Choroidal neovascularisation	Eye disorders	—	—
Influenza	Infections and infestations	—	—

Most-reported serious reactions: Myocardial infarction, Fall, Atrial fibrillation, Retinal haemorrhage, Pneumonia, Humerus fracture, Osteoarthritis, Transient ischaemic attack.

Data from ClinicalTrials.gov NCT02540954 adverse events section.

Sponsor's own description

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)

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.
   Kodjikian L, Arias Barquet L, Papp A, Kertes PJ, et al · · 2024 · cited 4× · PMID 38183525 · DOI 10.1007/s12325-023-02719-3