Study of a High-Dose Aflibercept in Participants With Diabetic Eye Disease

Regeneron Pharmaceuticals660 enrolled

Overview

The primary objective of the study is to determine if treatment with high-dose aflibercept (HD) at intervals of 12 or 16 weeks provides non-inferior best corrected visual acuity (BCVA) compared to aflibercept dosed every 8 weeks. The secondary objectives of the study are as follows: * To determine the effect of HD vs. aflibercept on anatomic and other visual measures of response * To evaluate the safety, immunogenicity, and pharmacokinetics (PK) of aflibercept

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

660

Conditions

Diabetic Macular Edema Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus

Interventions

afliberceptDRUG

Intravitreally (IVT) administered as a liquid formulation in a vial

High-dose afliberceptDRUG

Intravitreally (IVT) administered as a liquid formulation in a vial

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Diabetic macular edema (DME) with central involvement in the study eye * Best corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye with decreased vision determined to be primarily the result of DME * Willing and able to comply with clinic visits and study-related procedures * Provide informed consent signed by study participant or legally acceptable representative Extension Phase: All randomized patients that complete visit 26, week 96, as long as the patient 1) provides informed consent and 2) no treatment for DME has been given in the study eye other than the randomized study treatment. Key Exclusion Criteria: * Evidence of macular edema due to any cause other than diabetes mellitus in either eye * Active proliferative diabetic retinopathy in the study eye * IVT anti-VEGF treatment (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) or panretinal laser photocoagulation (PRP) /macular laser photocoagulation within 12 weeks (84 days) or intraocular or periocular corticosteroids within 16 weeks (112 days) of the screening visit in the study eye * Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy, etc.) at any time * Treatment with ocriplasmin (JETREA®) in the study eye at any time NOTE: Other Protocol Defined Inclusion/Exclusion Criteria Apply

Locations (138)

Outcomes

Primary Outcomes

Change From Baseline in Best Corrected Visual Acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] Letter Score) in the Study Eye at Week 48

Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).

Time frame: Baseline, Week 48

Secondary Outcomes

Percentage of Participants With a ≥2 Step Improvement From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Score at Week 48

The DRSS was assessed according to the following scale: 10 = Diabetic retinopathy (DR) absent, 14 = DR questionable, 15 = DR questionable, 20 = Micro-aneurysms only, 35 = Mild Non-proliferative diabetic retinopathy (NPDR), 43 = Moderate NPDR, 47 = Moderately severe NPDR, 53 = Severe NPDR, 61 = Mild Proliferative diabetic retinopathy (PDR), 65 = Moderate PDR, 71 = High-risk PDR, 75 = High-risk PDR, 81 = Advanced PDR: fundus partially obscured, center of macula attached, 85 = Advanced PDR: posterior fundus obscured, or center of macula detached, 90 = cannot grade, even sufficiently for level 81 or 85.

Time frame: Baseline, Week 48

Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline at Week 48

Time frame: Baseline, Week 48

Percentage of Participants With BCVA ≥69 Letters at Week 48

Data from ClinicalTrials.gov

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Regeneron Study Site

Phoenix, Arizona, United States

Regeneron Study Site

Arcadia, California, United States

Regeneron Study Site

Beverly Hills, California, United States

Regeneron Study Site

Campbell, California, United States

Regeneron Study Site

Encino, California, United States

Regeneron Study Site

Fullerton, California, United States

Regeneron Study Site

Huntington Beach, California, United States

Regeneron Study Site

Long Beach, California, United States

Regeneron Study Site

Palo Alto, California, United States

Regeneron Study Site

Pasadena, California, United States

...and 128 more locations

Time frame: At Week 48

Percentage of Participants Without Fluid at Foveal Center at Week 48

Retinal fluid status was evaluated using spectral domain optical coherence tomography (SD-OCT) on the study eye.

Time frame: At Week 48

Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 48

Central Retinal Thickness (CRT) was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

Time frame: Baseline, Week 48

Percentage of Participants Without Leakage on Fluorescein Angiography (FA) at Week 48

Leakage is the release of fluorescein dye from diseased retinal vessels.

Time frame: At Week 48

Change From Baseline in National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) Total Score at Week 48

Vision-specific quality of life is assessed with the NEI VFQ-25 (National Eye Institute Visual Function Questionnaire), i.e. a 25-item questionnaire that gives a score on a scale from 0 (worst) to 100 (best = no vision problems).

Time frame: Baseline, Week 48

Systemic Pharmacokinetics (PK) of Aflibercept as Assessed by Plasma Concentrations Through Week 48

Concentrations of Free Aflibercept in Plasma by Time and Treatment Group

Time frame: Through Week 48

Change From Baseline in BCVA in the Study Eye in Participants With Both Baseline and Week 48 BCVA

Time frame: Baseline, Week 48

Change From 8-weeks Post Initial Treatment Phase in BCVA in the Study Eye in Participants With Both 8-weeks Post Initial Treatment Phase BCVA and Week 48 BCVA

Time frame: Baseline, Week 48

Change From Baseline in BCVA (Region-specific Analysis) in the Study Eye at Week 60

Time frame: Baseline, Week 60

Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through Week 96

Number of participants with pre-existing immunoreactivity and treatment-emergent ADA response reported

Time frame: Through Week 96

Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Through Week 96

A TEAE is an AE starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days. Additionally, for patients who are still participating in the study (ie, have not been withdrawn and are continuing in the extension phase of the study) as of the week 96 visit all AEs up through the date of the week 96 visit were considered treatment-emergent.

Time frame: Through Week 96

Number of Participants With Any Serious TEAE Through Week 96

Time frame: Through Week 96

Number of Participants With Any TEAE Through Week 156

TEAEs are defined as AEs starting after the first dose of study drug to the last dose of study drug (active or sham) plus 30 days or week 156 visit, whichever was later.

Time frame: Through Week 156

Number of Participants With Any Serious TEAE Through Week 156

Time frame: Through Week 156