Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME)

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Macular Edema	Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) Other Names	Phase 3

Tracking Information

First Submitted Date	June 28, 2016
Last Update Posted Date	February 12, 2018
Actual Start Date	November 16, 2016
Anticipated Completion Date	November 05, 2019
Actual Primary Completion Date	September 03, 2018
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Change in ETDRS BCVA (Early Treatment Diabetic Retinopathy Study - best corrected visual acuity) letter score for the study eye from baseline to week 52 [Time Frame: From baseline to week 52]

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Change from baseline in ETDRS BCVA letter score for the study eye from baseline to week 100 [Time Frame: From baseline to week 100]

• Change from baseline in CRT (central retinal thickness) in the study eye from baseline to week 52 [Time Frame: From baseline to week 52]

• Change from baseline in CRT in the study eye from baseline to week 100 [Time Frame: From baseline to week 100]

• Proportion of subjects who gained 10 or more letters from baseline to week 52 [Time Frame: From baseline to week 52]

• Proportion of subjects who gained 10 or more letters from baseline to week 100 [Time Frame: From baseline to week 100]

• Proportion of subjects who gained 15 or more letters from baseline to week 52 [Time Frame: From baseline to week 52]

• Proportion of subjects who gained 15 or more letters from baseline to week 100 [Time Frame: From baseline to week 100]

• Proportion of subjects who lost 30 or more letters from baseline to week 52 [Time Frame: From baseline to week 52]

• Proportion of subjects who lost 30 or more letters from baseline to week 100 [Time Frame: From baseline to week 100]

• Number of participants with adverse events as a measure of safety and tolerability [Time Frame: Up to 100 weeks]

• Vital signs [Time Frame: Up to 100 weeks]

Original Secondary Outcome Measures

Study Design

Brief Title	Efficacy and Safety of Three Different Aflibercept Regimens in Subjects With Diabetic Macular Edema (DME)
Official Title	An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of Three Different Treatment Regimens of 2 mg Aflibercept Administered by Intravitreal Injections to Subjects With Diabetic Macular Edema (DME)
Brief Summary	To evaluate the efficacy of long-term treatment with 2 mg aflibercept via different intravitreal (IVT) treatment regimens to subjects with DME pretreated with 2 mg aflibercept every 8 weeks after 5 initial monthly injections for approximately 1 year or more (according to the EU label for the first year of treatment)
Detailed Description
Study Type	Interventional
Study Phase	Phase 3
Estimated Enrollment	462
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Conditions	Macular Edema
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) Other Names
Study Groups/Cohorts	Aflibercept [Treatment A] Patients receive 2 mg aflibercept per injection once every 8 weeks Aflibercept [Treatment B] Patients receive 2 mg aflibercept per injection with interval equal to or more than 8 weeks Aflibercept [Treatment C] Patients receive 2 mg aflibercept per injection on an as needed basis
Study Arms	Experimental Aflibercept [Treatment A] Patients receive 2 mg aflibercept per injection once every 8 weeks Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) Experimental Aflibercept [Treatment B] Patients receive 2 mg aflibercept per injection with interval equal to or more than 8 weeks Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321) Experimental Aflibercept [Treatment C] Patients receive 2 mg aflibercept per injection on an as needed basis Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Arm	Intervention/Treatment
Experimental Aflibercept [Treatment A] Patients receive 2 mg aflibercept per injection once every 8 weeks	Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Experimental Aflibercept [Treatment B] Patients receive 2 mg aflibercept per injection with interval equal to or more than 8 weeks	Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
Experimental Aflibercept [Treatment C] Patients receive 2 mg aflibercept per injection on an as needed basis	Biological : Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)

Recruitment Information

Recruitment Status:	Active, not recruiting
Enrollment	462
Completion Date	November 05, 2019
Eligibility Criteria:	Inclusion Criteria: - The subject's history of aflibercept treatment meets all of the following: 1. Treatment in the study eye was initiated with five monthly (-1 week /+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed and documented. 2. Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception will be allowed). 3. The interval between the last two pre-study injections was ≥ 8 weeks, and visual and anatomic outcomes have been stable over this interval. 4. The subject received the last IVT (intravitreal) injection of aflibercept in the study eye 8 weeks (±10 days) before the first planned treatment /randomization in this study. 5. Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment ever to enrollment into this study) was 1 year or longer. - To be met at initiation of pre-study aflibercept treatment: - Type-1 or -2 diabetes mellitus - Diagnosis of DME (diabetic macular edema) secondary to diabetes mellitus involving the center of the macula (defined as the area of the center subfield of OCT) in the study eye - Decrease in vision determined to be primarily the result of DME in the study eye - BCVA in the study eye of ETDRS letter score 73 to 24 (corresponding to a Snellen equivalent of approximately 20/40 to 20/320) Exclusion Criteria: At initiation of pre-study aflibercept treatment: - Previous treatment with anti-angiogenic drugs in study eye (e.g. pegaptanib sodium, bevacizumab, ranibizumab or aflibercept) within the last 12 weeks before initiation of aflibercept pre-study treatment At all of the following time points: i) Initiation of pre-study aflibercept treatment ii) Screening for this study iii) Baseline for this study - History of vitreoretinal surgery and/or including scleral buckling in the study eye - Prior treatment of the study eye with - Long acting steroids, either periocular or intraocular, in the preceding 120 days or - Iluvien intravitreal implant at any time - Active proliferative diabetic retinopathy (PDR), current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye - Cataract surgery within 90 days before aflibercept treatment in the study eye - Pre-retinal fibrosis involving the macula of 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 - Concurrent disease in the study eye, other than DME, that could compromise VA (visual acuity), require medical or surgical intervention during the study period, or could confound interpretation of the results (including advanced glaucoma, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause) - Administration of systemic anti angiogenic agents within 180 days before aflibercept treatment - Uncontrolled diabetes mellitus as defined by hemoglobin (Hb)A1c > 12.0% - Uncontrolled blood pressure (defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg while subject is sitting confirmed in two separate measurements) At all of the following time points: i) Screening for this study ii) Baseline for this study - Any ocular or periocular infection in the preceding 4 weeks in either eye - Filtration surgery for glaucoma in the past or likely to be needed in the future on the study eye - Uncontrolled glaucoma (defined as intraocular pressure [IOP] > 25 mmHg despite treatment with antiglaucoma medication) in the study eye - 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 renders the subject at high risk for treatment complications - Significant media opacities, including cataract, in the study eye that interferes with visual acuity, fundus photography or OCT (optical coherence tomography) imaging.
Gender	All
Age	18 Years to N/A
Accepts Healthy Volunteers	No
Contacts	Not Available
Listed Location Countries	Austria Canada Czechia France Germany Hungary Italy Lithuania Poland Portugal Slovakia Spain Switzerland United Kingdom Czech Republic

Administrative Information

NCT Number:	NCT02818998
Other Study ID Numbers	17613 2014-004938-25
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Bayer
Collaborators	Regeneron Pharmaceuticals
Investigators	Study Director Bayer Study Director Bayer