Long-Term Efficacy and Safety of Aflibercept Intravitreal Injections for the Treatment of Diabetic Macular Edema

Study Overview
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Brief Summary
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The Endurance Trial is a Phase IV open label clinical study to assess the need for ongoing intravitreal aflibercept injections after the 3-year VISTA DME (VGFT-OD-1009) endpoint. Subjects will be treated with intravitreal aflibercept injections pro re nata (PRN) based on the presence of CR-DME (Clinically Relevant-DME). In addition, subjects who meet re-treatment criteria will be eligible for focal laser treatment every 90 days

Detailed Description
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The Endurance3 Trial is a Phase IV open label study to assess the need for ongoing intravitreal aflibercept injections after the 3 year VISTA DME (VGFT-OD-1009) endpoint. Subjects will be treated with intravitreal aflibercept injections pro re nata (PRN) upon the presence of CR-DME (Clinically Relevant DME) as noted by OCT (Optical Coherence Tomography) imaging and examination. In addition, subjects who meet the re-treatment criteria will be eligible for focal laser treatment every 90 days.

Official Title
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Long-Term Efficacy and Safety of Aflibercept Intravitreal Injections for the Treatment of Diabetic Macular Edema in Subjects Who Completed the Three Year VISTA-DME Trial

Conditions
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Clinically Significant Diabetic Macular Edema

Intervention / Treatment
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* Procedure: Assigned Intervention
* Drug: aflibercept 2.0 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled and completed VISTA DME (VGFT-OD-1009) clinical trial Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Enrollment in the trial within 12 weeks of trial activation Exclusion Criteria: Prior treatment with anti-VEGF therapy in the study eye within 28 days of baseline Pregnant or breast-feeding women Sexually active ment or women of childbearing potential who are unwilling to practice adequate contraception during the study

Ages Eligible for Study
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Minimum Age: 18 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: Open-Label Arm<br>2mg Aflibercept, as needed, intravitreal administration. All subjects will be treated with intravitreal (IVT) aflibercept injections as needed in the presence of clinically relevant diabetic macular edema (CR-DME). If CR-DME is not present the subject will not receive an IVT aflibercept injection and will be observed. If a subject has recurrent CR-DME they will receive an IVT aflibercept 2.0 mg injection and interval between visits will be reduced to 4 weeks. At week 12 through end of study, all subjects will be evaluated for focal laser treatment. | Procedure: Assigned Intervention<br>* All subjects receiving PRN IVT aflibercept injections will be evaluated for focal laser treatment beginning at week 12 through the end of the study as assigned intervention. If the subject meets any of the criteria for focal laser treatment (FLT), fluorescein angiography (FA) will be performed to guide the focal laser treatment. Focal laser treatment and focal laser re-treatment will be administered no more than once every 90 days.<br>* Other names: FLT;Drug: aflibercept 2.0 mg<br>* If a subject has recurrent CR-DME they will receive an IVT aflibercept injection<br>* Other names: VEGF-Trap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of intravitreal aflibercept injections in 52 weeks |  | 12 months | 
| Proportion of subjects receiving 0 aflibercept injections in 52 weeks |  | 12 months | 
| Longer-term efficacy of aflibercept intravitreal injections as assessed by the mean number of injections in 52 weeks |  | 12 months | 
| Safety of ongoing aflibercept intravitreal injections as assessed by the incidence and severity of ocular and systemic adverse events |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vision Change | Mean change in visual acuity from baseline to week 52 | 12 months | 
| Vision loss | Proportion of subjects with gain or loss of 0 to 5 letters from baseline to week 52 | 12 months | 
| Change in central retinal thickness | Mean change in central retinal thickness from baseline to week 52 | 12 months | 
| Development of clinically relevant diabetic macular edema | Percentage of subjects with no clinically relevant diabetic macular edema seen on SD-OCT from baseline to week 52 | 12 months | 
| Evaluation of Diabetic Retinopathy (Proportion of subjects with stable, worsened, or improved diabetic retinopathy as identified by eye examination and imaging) | Proportion of subjects with stable, worsened, or improved diabetic retinopathy as identified by eye examination and imaging | 12 months | 
| Role of focal laser treatment in management of DME (Proportion of subjects that receive focal laser treatment and mean number of intravitreal aflibercept injections before and after receiving focal laser treatment) | Proportion of subjects that receive focal laser treatment and mean number of intravitreal aflibercept injections before and after receiving focal laser treatment | 12 months | 
| Ocular and systemic adverse events | Incidence and severity of ocular and systemic adverse events as identified by eye examinations, imaging, and subject reporting | 12 months |