Efficacy and Safety of Aflibercept as Mono-therapy in Treat and Extend Regimen for DME Patients in Taiwan

Study Overview
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Brief Summary
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Phase IIIb, multicenter, open-label, prospective, interventional study to assess the potential benefit of Aflibercept treatment administered IVT at a dosage of 2 mg with five monthly loading doses and then treat and extend over 48 weeks, with the primary endpoint as BCVA assessed at Week 52.

Official Title
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A Multicenter, Open-label, Prospective, Interventional Study to Assess the Efficacy and Safety of Aflibercept as Mono-therapy in Treat and Extend Regimen for DME Patients in Taiwan

Conditions
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Center-involved Diabetic Macular Edema

Intervention / Treatment
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* Drug: Aflibercept Injection [Eylea]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 20 years old with type 1 or 2 diabetes mellitus Subjects with DME secondary to diabetes mellitus involving the center of the macula (defined as the area of the center subfield of optical coherence tomography [OCT]) in the study eye Retinal thickness as assessed by OCT above (>) 300 um in the study eye BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye Would be able to comply with clinic visits and study-related procedures Would be able to provide a signed informed consent form (ICF) Exclusion Criteria: Ocular conditions with a poorer prognosis in the fellow eye than in the study eye History of vitreoretinal surgery and/or including scleral buckling in the study eye Laser photocoagulation (pan-retinal or macular) in the study eye within 90 days of Day 1 Against the background of a relevant number of previous macular laser treatments the investigator's point of view was that the subjects had no potential to benefit from laser treatments (e.g., if too many laser treatments were applied in the past) Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of Day 1 Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, bevacizumab, ranibizumab etc.) within 90 days of Day 1 High risk proliferative diabetic retinopathy (PDR) in the study eye upon physician's discretion High risk = the presence of any of the following: Vitreous hemorrhage New vessels on the disk >1/3 disk diameter New vessels elsewhere >1/2 disk diameter History of idiopathic or autoimmune uveitis in the study eye Cataract surgery within 90 days before Day 1 in the study eye Aphakia in the study eye Yttrium-aluminium-garnet (YAG) capsulotomy in the study eye within 30 days before Day 1 Any other intraocular surgery within 90 days of Day 1 in the study eye Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or on OCT that is thought to affect central vision Current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye Pre-retinal fibrosis involving the macula in the study eye Structural damage to the center of the macula in the study eye that was likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates Ocular inflammation including trace or above in the study eye Evidence of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye Filtration surgery for glaucoma in the past or likely to be needed in the future on the study eye Intraocular pressure (IOP) ≥ 25 mmHg in the study eye High myopia (≤ -6.0 diopters or axial length of ≥26.5 mm) prior to any possible refractive or cataract surgery Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study period, or could confound interpretation of the results (including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause) Only 1 functional eye even if that eye was otherwise eligible for the study Ocular media of insufficient quality to obtain fundus and OCT images Current treatment for a serious systemic infection Administration of systemic anti-angiogenic agents within 180 days before Day 1 Uncontrolled diabetes mellitus, as defined by Hemoglobin A1c; (glycosylated hemoglobin) (HbA1c)>10%. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg while subject was sitting) History of either cerebral vascular accident and/or myocardial infarction within 180 days prior to Day 1 Renal failure requiring dialysis or renal transplant History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, might affect interpretation of the results of the study, or rendered the subject at high risk for treatment complications Pregnant or breast-feeding women Sexually active men or women of childbearing potential who were unwilling to practice adequate contraception during the study were excluded (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly or diaphragm plus contraceptive sponge, foam, or jelly). Allergy to fluorescein Participation in an investigational study within 30 days prior to screening visit that involved treatment with any drug (excluding vitamins and minerals) or device

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal aflibercept<br>Intravitreal injection of aflibercept 2.0mg/0.05 ml Aflibercept was administered with 5 monthly loadings followed by treat-and-extend with a 4-week interval increment/decrement with maxima cap at 12 weeks to visual/anatomic stability. | Drug: Aflibercept Injection [Eylea]<br>* Intravitreal aflibercept Injection 2.0mg/0.05 ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of best corrected visual acuity (BCVA) from baseline to week 52 | BCVA is measured by ETDRS chart | baseline to week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in central subfoveal thickness (CST) from baseline to week 52. | Central subfoveal thickness (CST) as assessed by OCT | baseline to week 52 | 
| Mean/medium number of injection from baseline to week 52 | Mean/medium number of intravitreal aflibercept injection from baseline to week 52 | baseline to week 52 | 
| Proportion of subjects who gained > 15 ETDRS letters from baseline to week 52 | BCVA is measured by ETDRS chart | baseline to week 52 | 
| Proportion of subjects with > 2-step improvement in DRSS from baseline to week 52 | DR level as assessed by diabetic retinopathy severity score (DRSS) | baseline to week 52 | 
| Proportion of subjects demonstrating retina dry at week 20 and week 52 | Retina dry as assessed by OCT | week 20 and week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-VEGF, intravitreal aflibercept, diabetic macular edema, Treat-and-Extend regimen