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

Phase 3

Active, not recruiting

Conditions: Neovascular Age-Related Macular Degeneration

Interventions: Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
Drug: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)

Registration Number: NCT04423718

Lead Sponsor: Bayer

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 1011

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aflibercept 2q8	Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)	In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental)
Aflibercept 2q8	Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)	In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental)
Aflibercept HDq12	Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)	Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.
Aflibercept HDq16	Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)	Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16	At Week 16
Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48	At Week 48
Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48	At Week 48
Change in Total Lesion Area From Baseline to Week 48	At baseline and Week 48
Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60	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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)	Up to 156 weeks
Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48	At baseline and Week 48
Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48	At baseline and Week 48
Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48	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)
Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48	Up to Week 48
Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study	Up to week 96
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48	At baseline and Week 48

Trial Locations

Locations (235): University Multiprofile Hospital For Active Treatment 'Alexandrovska' EAD
🇧🇬
Sofia, Bulgaria
Arizona Retina and Vitreous Consultants - North Phoenix
🇺🇸
Phoenix, Arizona, United States
Retina Consultants of Orange County
🇺🇸
Fullerton, California, United States
University of California San Diego (UCSD)
🇺🇸
La Jolla, California, United States
Northern California Retina-Vitreous Associates
🇺🇸
Mountain View, California, United States
California Eye Specialists Medical Group, Inc.
🇺🇸
Pasadena, California, United States
Retina Consultants San Diego
🇺🇸
Poway, California, United States
Retina Consultants of Southern California
🇺🇸
Redlands, California, United States
Kaiser Permanente Riverside Medical Center
🇺🇸
Riverside, California, United States
Retina Consultants of Southern Colorado, PC
🇺🇸
Colorado Springs, Colorado, United States
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University Multiprofile Hospital For Active Treatment 'Alexandrovska' EAD
🇧🇬Sofia, Bulgaria