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

Phase 4

Completed

• Conditions: Clinically Significant Diabetic Macular Edema
• Interventions: Procedure: Assigned Intervention; Drug: aflibercept 2.0 mg

• Registration Number: NCT02734407
• Lead Sponsor: Retina-Vitreous Associates Medical Group

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-12-16
• Study Start: 2015-01
• Study First Submitted QC: 2016-04-05
• Study First Posted: 2016-04-12
• Primary Completion: 2017-09-27
• Study Completion: 2017-09-27
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-25
• Last Update Posted: 2019-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-Label Arm	aflibercept 2.0 mg	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.
Open-Label Arm	Assigned Intervention	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.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects receiving 0 aflibercept 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
Mean number of intravitreal 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

Secondary Outcome Measures

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