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 (PULSAR)

Bayer

Status and phase: Active, not recruiting; Phase 3

Conditions: Neovascular Age-Related Macular Degeneration

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04423718

20968

2019-003851-12 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 1,011 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,011 participants in 3 patient groups

Aflibercept 2q8

Active Comparator group

Description:

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)

Treatment:

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

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

Aflibercept HDq12

Experimental group

Description:

Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.

Treatment:

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

Aflibercept HDq16

Experimental group

Description:

Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.

Treatment:

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