Phase 3 N=1,009 Randomized Quadruple-blind Treatment

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

Neovascular Age-Related Macular Degeneration

Bottom Line

View on ClinicalTrials.gov: NCT04423718 ↗

Enrolled (actual)

1,009

Serious AEs

24.7%

Results posted

Sep 2023

Primary outcome: Primary: Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 — 7.03; 6.06; 5.89 scores on a scale — p=0.0009

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321) (Drug); Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321) (Drug)
Age: Adult, Older Adult · 50+ yrs
Sex: All
Sponsor: Bayer
Primary completion: Jul 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48	7.03; 6.06; 5.89	0.0009 sig
SECONDARY Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60	7.23; 6.37; 6.31	0.0002 sig
SECONDARY Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16	51.6; 61.6; 65.0; 63.3	0.0002 sig
SECONDARY Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48	22.1; 20.7; 21.7	0.5704
SECONDARY Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48	57.9; 56.9; 54.3	0.9554
SECONDARY Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48	-2.43; -3.65; -2.91	0.0009 sig
SECONDARY Change in Total Lesion Area From Baseline to Week 48	0.09; -0.46; -0.35	0.0287 sig
SECONDARY Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48	59.4; 71.1; 66.8	0.0015 sig
SECONDARY Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48	-136.25; -147.37; -146.76	0.0283 sig
SECONDARY Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48	4.22; 3.50; 3.35	0.3817
SECONDARY Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48	NA; NA; NA; 0.03; 0.14; 0.13	—
SECONDARY Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response	8; 14; 13; 27; 0; 0	—

Summary

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.

Eligibility Criteria

Inclusion Criteria

Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye.
Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye.
BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye.
Decrease in BCVA determined to be primarily the result of nAMD in the study eye.
Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies.
Other protocol-specified inclusion criteria.

Additional inclusion criteria for Year 3:

At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92).
Participant is enrolled at a site that participates in the extension period.

Exclusion Criteria

Causes of CNV other than nAMD in the study eye.
Scar, fibrosis, or atrophy involving the central subfield in the study eye.
Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye.
Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye.
History of idiopathic or autoimmune uveitis in the study eye.
Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery.
History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye.
Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization.
Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg).
Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins.
Other protocol-specified exclusion criteria

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04423718). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.