Trial Outcomes & Findings for Long-Term Efficacy & Safety of Aflibercept IVT for the Treatment of DME in Subjects Who Completed the VISTA-DME Trial (NCT NCT02299336)

Last Updated: 2019-06-04

Results Overview

Measured by evaluating mean number of injections required for subjects who were enrolled and completed the 3-year VISTA DME (VGFT-OD-1009) trial

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

Week 104

Results posted on

2019-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	PRN (Pro re Nata) 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Overall Study STARTED	60
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	PRN (Pro re Nata) 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Overall Study Withdrawal by Subject	11
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Lost to Follow-up	1

Baseline Characteristics

Long-Term Efficacy & Safety of Aflibercept IVT for the Treatment of DME in Subjects Who Completed the VISTA-DME Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Age, Continuous	62.3 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants
Glycated Hemoglobin	7.5 Percent STANDARD_DEVIATION 1.1 • n=5 Participants
Duration of Diabetes	18.6 years STANDARD_DEVIATION 10.6 • n=5 Participants
Early Treatment Diabetic Retinopathy Study Best-Corrected Visual Acuity	69.6 letters STANDARD_DEVIATION 13.4 • n=5 Participants
Central Retinal Thickness	290 Microns STANDARD_DEVIATION 88.8 • n=5 Participants

PRIMARY outcome

Timeframe: Week 104

Measured by evaluating mean number of injections required for subjects who were enrolled and completed the 3-year VISTA DME (VGFT-OD-1009) trial

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=46 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Number of Intravitreal Aflibercept Injections for Subjects Who Were Enrolled and Completed the 3-year VISTA DME (VGFT-OD-1009) Trial	9.5 injections Standard Error 6.7

SECONDARY outcome

Timeframe: Week 52, Week 104

Population: All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.

Evaluate the mean change over time in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity at week 52 from baseline and at week 104 from baseline. Participants were challenged with reading letters on lines of an eye chart (5 letters per line) in standardized lighting conditions. Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity From Baseline to Week 52 and Baseline to Week 104 52 Weeks	0.61 letters Standard Error 1.28
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity From Baseline to Week 52 and Baseline to Week 104 104 Weeks	0.83 letters Standard Error 1.66

SECONDARY outcome

Timeframe: Before First Focal Laser Treatment (FLT) at Week 12 or later; After First FLT at up to 104 weeks

Population: Only participants who were eligible for focal laser treatment were analyzed.

Measure the role of focal laser treatment (fluorescein angiography-guided, if applicable) in decreasing the treatment burden among subjects who require ongoing aflibercept treatment in the management of diabetic macular edema.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=27 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Number of Intravitreal Aflibercept Injections Before and After Receiving First Focal Laser Application. Injections Before First Focal Laser	7.5 Injections Standard Deviation 3.7
Mean Number of Intravitreal Aflibercept Injections Before and After Receiving First Focal Laser Application. Injections After First Focal Laser	6.7 Injections Standard Deviation 4.2

SECONDARY outcome

Timeframe: Week 52, Week 104

Evaluate the percentage of subjects with a gain or loss in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letters in patients treated with aflibercept from baseline to week 52 and baseline to week 104

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Percentage of Subjects With Gain or Loss of 0 to 5 Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Letters From Baseline to Week 52 and Baseline to Week 104 Week 52	35 Participants
Percentage of Subjects With Gain or Loss of 0 to 5 Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Letters From Baseline to Week 52 and Baseline to Week 104 Week 104	30 Participants

SECONDARY outcome

Timeframe: Week 52, Week 104

Evaluate the mean change in central retinal thickness from baseline to week 52 and baseline to week 104 in patients treated with aflibercept.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Change in Central Retinal Thickness From Baseline to Week 52 and Baseline to Week 104. Week 52	-7 Microns Standard Error 8.6
Mean Change in Central Retinal Thickness From Baseline to Week 52 and Baseline to Week 104. Week 104	1 Microns Standard Error 11.53

SECONDARY outcome

Timeframe: Week 52, Week 104

Evaluate the number of subjects with no clinically-relevant diabetic macular edema (as defined in the protocol) on spectral domain optical coherence tomography from baseline to week 52 and baseline to week 104 in patients treated with aflibercept.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Number of Subjects With no Clinically-relevant Diabetic Macular Edema (as Defined in the Protocol) on Spectral Domain Optical Coherence Tomography From Baseline to Week 52 and Baseline to Week 104. Week 52	39 Participants
Number of Subjects With no Clinically-relevant Diabetic Macular Edema (as Defined in the Protocol) on Spectral Domain Optical Coherence Tomography From Baseline to Week 52 and Baseline to Week 104. Week 104	29 Participants

SECONDARY outcome

Timeframe: Week 52, Week 104

Number of subjects with stable, worsened, or improved diabetic retinopathy through 104 weeks.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 52 · Worsened Diabetic Retinopathy	5 Participants
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 52 · Stable Diabetic Retinopathy	46 Participants
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 52 · Improved Diabetic Retinopathy	3 Participants
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 104 · Worsened Diabetic Retinopathy	15 Participants
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 104 · Stable Diabetic Retinopathy	27 Participants
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy Week 104 · Improved Diabetic Retinopathy	4 Participants

SECONDARY outcome

Timeframe: Week 52, Week 104

Number of subjects that receive focal laser treatment from baseline to week 52 and from baseline to week 104.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Number of Subjects That Receive Focal Laser Treatment. Week 104	27 Participants
Number of Subjects That Receive Focal Laser Treatment. Week 52	25 Participants

SECONDARY outcome

Timeframe: 104 weeks

Population: All participants receiving laser were included in analysis.

Evaluation of the effect of laser on Early Treatment Diabetic Retinopathy Study best-corrected visual acuity outcomes. Participants were challenged with reading letters on lines of an eye chart (5 letters per line) in standardized lighting conditions. Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=27 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Before and After Focal Laser Therapy Before First FLT	0.4 letters Standard Deviation 6.2
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Before and After Focal Laser Therapy After First FLT	0.3 letters Standard Deviation 11.9

SECONDARY outcome

Timeframe: 104 weeks

Evaluate the mean change in central retinal thickness before and after first focal laser treatment in patients treated with pro re nata aflibercept.

Outcome measures

Outcome measures
Measure	PRN (Pro re Nata) n=60 Participants 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Mean Change in Central Retinal Thickness Before and After First Focal Laser Treatment Before First FLT	-8.5 microns Standard Error 52.6
Mean Change in Central Retinal Thickness Before and After First Focal Laser Treatment After First FLT	-6.8 microns Standard Error 41.6

SECONDARY outcome

Timeframe: Week 52, Week 104

Population: This analysis was never performed because we were logistically unable to collect the data.

Mean number of injections in 52 weeks and 104 weeks based on quantification of ischemic areas

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52, Week 104

Population: This analysis was never performed because we were logistically unable to collect the data.

Mean change in visual acuity from baseline to week 52 and baseline to week 104 based on quantification of ischemic areas

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52, Week 104

Population: This analysis was never performed because we were logistically unable to collect the data.

Mean change in central retinal thickness from baseline to week 52 based on quantification of ischemic areas

Outcome measures

Outcome data not reported

Adverse Events

PRN (Pro re Nata)

Serious events: 19 serious events

Other events: 26 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	PRN (Pro re Nata) n=60 participants at risk 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Cardiac disorders Myocardial Infarction	3.3% 2/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Deep vein thrombosis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Stroke	3.3% 2/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Cardiac disorders Worsening congestive heart failure	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Acute vision loss secondary to vitreous hemorrhage	3.3% 2/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Acute vision loss due to worsening cataract	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Infections and infestations Worsening staph infection	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Gastrointestinal disorders Acute gastroenteritis	3.3% 2/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Skin and subcutaneous tissue disorders Cellulitis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Cardiac disorders Worsening arrhythmia	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Renal and urinary disorders Chronic kidney disease	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Cardiac disorders Worsening coronary artery disease	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Hypotension	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Infections and infestations Pneumonia	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Blocked fistula	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Infections and infestations Flu	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Blocked artery	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Vascular disorders Accelerated hypertension	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Infections and infestations Osteomyelitis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Psychiatric disorders Depression	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Hepatobiliary disorders Cholecystitis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.

Other adverse events

Other adverse events
Measure	PRN (Pro re Nata) n=60 participants at risk 2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks Aflibercept: pro re nata (PRN) Focal Laser: Focal laser administered based on pre-specified criteria
Eye disorders Vitreous hemorrhage	15.0% 9/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Neovascularization elsewhere	3.3% 2/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Neovascularization of the disc	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Worsening cataract	13.3% 8/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Corneal abrasion	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Subconjunctival hemorrhage	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Superficial punctate keratitis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Eye swelling post-cataract extraction	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Posterior vitreous detachment	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Floaters	8.3% 5/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Visual disturbance	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Epiphora	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Posterior capsule opafication	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Iritis	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Eye pain	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Vitreous debris	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Optic nerve pallor	1.7% 1/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Decreased vision	6.7% 4/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.
Eye disorders Ocular sensitivity	8.3% 5/60 • 104 weeks. Adverse events were assessed at every study visit during the 2-year study.

Additional Information

Dr. Charles C. Wykoff

Retina Consultants of Houston

Phone: 7135243434

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place