Who is sponsoring NCT04423718?

NCT04423718 is sponsored by Bayer.

What drugs are being tested in NCT04423718?

Interventions in NCT04423718: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321), Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321).

What condition does NCT04423718 study?

NCT04423718 studies Neovascular Age-Related Macular Degeneration.

Is NCT04423718 still recruiting?

NCT04423718 is currently completed. Last updated 29 August 2025.

Are results published for NCT04423718?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2025-08-29 · How we verify

NCT04423718: PULSAR

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Study of the Effects of High Dose Aflibercept Injected Into the Eye of Patients With an Age-related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye

Completed Phase 3 Results posted Last updated 29 August 2025

What this trial tests

Phase 3 trial testing Aflibercept High Dose VEGF Trap-Eye (BAY86-5321) in Neovascular Age-Related Macular Degeneration in 1,011 participants. Completed in 7 August 2024.

Timeline

11 August 2020

Primary endpoint
27 July 2022

7 August 2024

Quick facts

Lead sponsor	Bayer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	1,011
Start date	11 August 2020
Primary completion	27 July 2022
Estimated completion	7 August 2024
Sites	235 locations across Italy, Japan, Taiwan, South Korea, Russia, Estonia, Lithuania, Bulgaria

Drugs / interventions tested

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

Conditions studied

Neovascular Age-Related Macular Degeneration — all drugs for Neovascular Age-Related Macular Degeneration →

Sponsor

Bayer — full company profile →

Who can join

50 and older, any sex, with Neovascular Age-Related 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.

Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 Primary · At baseline and Week 48

Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).

Group	Value	95% CI
Aflibercept 2q8	7.03	± 0.74
Aflibercept HDq12	6.06	± 0.77
Aflibercept HDq16	5.89	± 0.72

Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 Secondary · At baseline and Week 60

Visual function of the study eye was assessed at a distance of 4 meters using the ETDRS BCVA letter score. BCVA scale range is 0 (worst) to 100 (best).

Group	Value	95% CI
Aflibercept 2q8	7.23	± 0.68
Aflibercept HDq12	6.37	± 0.74
Aflibercept HDq16	6.31	± 0.66

Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 Secondary · At Week 16

Group	Value	95% CI
Aflibercept 2q8	51.6
Aflibercept HDq12	61.6
Aflibercept HDq16	65.0
All Aflibercept HD	63.3

Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 Secondary · At baseline and Week 48

Group	Value	95% CI
Aflibercept 2q8	22.1
Aflibercept HDq12	20.7
Aflibercept HDq16	21.7

Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 Secondary · At Week 48

Group	Value	95% CI
Aflibercept 2q8	57.9
Aflibercept HDq12	56.9
Aflibercept HDq16	54.3

Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 Secondary · At baseline and Week 48

Group	Value	95% CI
Aflibercept 2q8	-2.43	± 0.31
Aflibercept HDq12	-3.65	± 0.28
Aflibercept HDq16	-2.91	± 0.29

Change in Total Lesion Area From Baseline to Week 48 Secondary · At baseline and Week 48

Group	Value	95% CI
Aflibercept 2q8	0.09	± 0.22
Aflibercept HDq12	-0.46	± 0.19
Aflibercept HDq16	-0.35	± 0.20

Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 Secondary · At Week 48

Group	Value	95% CI
Aflibercept 2q8	59.4
Aflibercept HDq12	71.1
Aflibercept HDq16	66.8

Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 Secondary · At baseline and Week 48

Group	Value	95% CI
Aflibercept 2q8	-136.25	± 4.24
Aflibercept HDq12	-147.37	± 4.01
Aflibercept HDq16	-146.76	± 3.76

Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 Secondary · At baseline and Week 48

NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)

Group	Value	95% CI
Aflibercept 2q8	4.22	± 0.70
Aflibercept HDq12	3.50	± 0.70
Aflibercept HDq16	3.35	± 0.72

Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 Secondary · Up to Week 48

Week 4

Group	Value	95% CI
Aflibercept 2q8	NA	± NA
Aflibercept HDq12	NA	± NA
Aflibercept HDq16	NA	± NA

Visit 5: within 3 to 7 days after the Week 8

Group	Value	95% CI
Aflibercept 2q8	0.03	± 70.29
Aflibercept HDq12	0.14	± 78.69
Aflibercept HDq16	0.13	± 82.50

Week 12

Group	Value	95% CI
Aflibercept 2q8	NA	± NA
Aflibercept HDq12	0.02	± 81.35
Aflibercept HDq16	0.02	± 84.06

Week 28

Group	Value	95% CI
Aflibercept 2q8	NA	± NA
Aflibercept HDq12	NA	± NA
Aflibercept HDq16	NA	± NA

Week 48

Group	Value	95% CI
Aflibercept 2q8	NA	± NA
Aflibercept HDq12	NA	± NA
Aflibercept HDq16	NA	± NA

Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Secondary · Up to week 96

Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Low (< 1000)

Group	Value	95% CI
Aflibercept 2q8	8
Aflibercept HDq12	14
Aflibercept HDq16	13
All Aflibercept HD	27

Treatment-emergent positive or Treatment-boosted, maximum ADA titers - Moderate (1000-10000)

Group	Value	95% CI
Aflibercept 2q8	0
Aflibercept HDq12	0
Aflibercept HDq16	0
All Aflibercept HD	0

Treatment-emergent positive or Treatment-boosted, maximum ADA titers - High (> 10000)

Group	Value	95% CI
Aflibercept 2q8	0
Aflibercept HDq12	0
Aflibercept HDq16	0
All Aflibercept HD	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Through Week 96, from first dosing up to 30 days after last dosing (active or sham procedure). Through Week 156, from first dosing up to 30 days after last dosing (active or sham procedure) or the Week 156 visit, whichever was later. AE reporting for all-cause mortality considers all deaths occurred at any time during the study before the last contact.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Aflibercept 2q8 (Week 0- 96)

Serious: 69/336 (21%)

Deaths: 12/336

Aflibercept HDq12 (Week 0- 96)

Serious: 83/335 (25%)

Deaths: 11/335

Aflibercept HDq16 (Week 0- 96)

Serious: 72/338 (21%)

Deaths: 7/338

All Aflibercept HD (Week 0- 96)

Serious: 155/673 (23%)

Deaths: 18/673

Aflibercept 2q8/HD (Week 0- 156)

Serious: 49/208 (24%)

Deaths: 4/208

Aflibercept HDq12 (Week 0- 156)

Serious: 61/210 (29%)

Deaths: 7/210

Aflibercept HDq16 (Week 0- 156)

Serious: 61/207 (29%)

Deaths: 2/207

All Aflibercept HD (Week 0- 156)

Serious: 122/417 (29%)

Deaths: 9/417

Serious adverse events (230 terms)

Reaction	System	Aflibercept 2q8 (Week 0- 96)	Aflibercept HDq12 (Week 0-…	Aflibercept HDq16 (Week 0-…	All Aflibercept HD (Week 0…	Aflibercept 2q8/HD (Week 0…	Aflibercept HDq12 (Week 0-…	Aflibercept HDq16 (Week 0-…	All Aflibercept HD (Week 0…
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—
Cataract	Eye disorders	—	—	—	—	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Retinal detachment	Eye disorders	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—	—
Retinal haemorrhage	Eye disorders	—	—	—	—	—	—	—	—
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—	—	—	—
Angina unstable	Cardiac disorders	—	—	—	—	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—
Death	General disorders	—	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—
Intraocular pressure increased	Investigations	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—	—
Aortic valve stenosis	Cardiac disorders	—	—	—	—	—	—	—	—
Arrhythmia	Cardiac disorders	—	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Aflibercept 2q8 (Week 0- 96)	Aflibercept HDq12 (Week 0-…	Aflibercept HDq16 (Week 0-…	All Aflibercept HD (Week 0…	Aflibercept 2q8/HD (Week 0…	Aflibercept HDq12 (Week 0-…	Aflibercept HDq16 (Week 0-…	All Aflibercept HD (Week 0…
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—
Cataract	Eye disorders	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—	—
Visual acuity reduced	Eye disorders	—	—	—	—	—	—	—	—
Retinal haemorrhage	Eye disorders	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Intraocular pressure increased	Investigations	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Vitreous floaters	Eye disorders	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Cataract, Osteoarthritis, Retinal detachment, Urinary tract infection, Pulmonary embolism, Angina pectoris, Coronary artery disease.

Data from ClinicalTrials.gov NCT04423718 adverse events section.

Sponsor's own description

In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood into the light sensitive lining inside the eye (retina). The fluid buildup causes the central part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken (edema), which distorts vision.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications.
Zhang J, Zhang J, Zhang C, Zhang J, et al · · 2022 · cited 161× · PMID 36359761 · DOI 10.3390/cells11213362
Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.
Lanzetta P, Korobelnik JF, Heier JS, Leal S, et al · · 2024 · cited 158× · PMID 38461841 · DOI 10.1016/s0140-6736(24)00063-1
Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives.
Kim HM, Woo SJ. · · 2021 · cited 117× · PMID 33467779 · DOI 10.3390/pharmaceutics13010108
Macular neovascularization and polypoidal choroidal vasculopathy: phenotypic variations, pathogenic mechanisms and implications in management.
Cheung CMG. · · 2024 · cited 22× · PMID 37803144 · DOI 10.1038/s41433-023-02764-w
Incidence of severe rise in intraocular pressure after intravitreous injection of aflibercept with prefilled syringes.
Dingerkus VLS, Somfai GM, Kinzl S, Orgül SI, et al · · 2022 · cited 13× · PMID 36307473 · DOI 10.1038/s41598-022-23039-6
Seeing the Future: A Review of Ocular Therapy.
Whalen M, Akula M, McNamee SM, DeAngelis MM, et al · · 2024 · cited 12× · PMID 38391665 · DOI 10.3390/bioengineering11020179
High-Dose Aflibercept for Neovascular AMD and DME in Suboptimal Responders to Standard-Dose Aflibercept.
Nielsen JS, Roberts CL, Saggau DD, Alliman KJ. · · 2023 · cited 9× · PMID 37006663 · DOI 10.1177/24741264221150345
Real-world efficacy and safety of 8 mg aflibercept in neovascular AMD: a case series.
Sambhara D, Vakharia P, Eichenbaum DA. · · 2025 · cited 8× · PMID 39947712 · DOI 10.1136/bmjophth-2024-002091

Verify or expand the search:

Other recruiting trials for Neovascular Age-Related Macular Degeneration

Currently open trials in the same condition.

NCT06491914 — A Phase 3b, Single-Arm Study of Aflibercept 8 mg Dosed Every 4 Weeks in Adult Participants With Neovascular Age-Related · Phase 3 · active not recruiting
NCT06223958 — Study to Evaluate the Efficacy and Safety of Intravitreal OTX-TKI (Ocular Therapeutix) (Axitinib Implant) in Subjects Wi · Phase 3 · active not recruiting
NCT03683251 — Extension Study for the Port Delivery System With Ranibizumab (Portal) · Phase 3 · recruiting

Other Bayer trials

Trials by the same sponsor.

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NCT07450599 — A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Befo · Phase 2 · not yet recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT04423718 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Bayer
Last refreshed: 29 August 2025

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04423718.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing