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

May 15, 2019 updated by: Charles C Wykoff, PhD, MD, Greater Houston Retina Research

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

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; NCT01363440) end-point. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigational product is aflibercept, which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. Vials must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions.

The injection volume will be 50μL (0.05 mL) and will be administered to the subjects by IVT injection.

Throughout the trial, subjects will be treated with intravitreal aflibercept injections PRN in the presence of CR-DME; this is defined as DME that the treating investigator believes is limiting visual function.

All subjects will initially be evaluated every 4 weeks (28 days) for CR-DME and treated PRN. If CR-DME is present the subject will receive IVT aflibercept injection. If CR-DME is not present the subject will not receive an IVT aflibercept injection and will be observed.

At any point throughout the study, once a subject has been evaluated and observed (with no IVT aflibercept) for a total of 8 weeks (3 consecutive monthly visits), the interval between visits will be increased to 8 weeks.

After an additional 24 weeks (3 consecutive visits, every 8 weeks) without an IVT aflibercept injection, the interval between visits will be increased to 12 weeks.

If a subject has recurrent CR-DME they will receive an IVT aflibercept injection and the interval between visits will reduce back to 4 weeks. Subjects can again extend the interval between visits to 8 weeks once they have not received an IVT aflibercept injection for a total of 8 weeks (3 consecutive visits) as described above. Extension to 12 weeks is then performed as above.

Starting at week 52, once a subject has extended to a 12 week interval, if CR-DME is not present the subject will not receive an IVT aflibercept injection and will be extended to a 16 week interval. Once at a 16 week interval, if CR-DME is not present the subject will not receive an IVT aflibercept injection and will be extended to a 20 week interval. At any point past a 12 week interval extension, if a subject has recurrent CR-DME they will receive an IVT aflibercept injection and the interval for the next visit will be reduced at investigator discretion to be either 12 or 16 weeks. If the interval is needed to be reduced to below 12 weeks, the subject will return to a 4 or 8 week interval, at investigator discretion and return to the protocol above.

All subjects receiving PRN IVT aflibercept injections will be evaluated for focal laser treatment beginning at week 12 through the end of the study. 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.

When a subject receives ≥ 2 IVT aflibercept injections in ≤ 24 weeks FLT will be applied. Once the initial session of FLT is applied subjects are eligible for FLT re-treatment after 90 days, when they have received ≥ 2 IVT aflibercept injections within the prior 90 day period.

FLT will be applied to:

  1. All leaking microaneurysms.
  2. Grid to all areas of diffuse leakage.
  3. Grid to all areas of retinal ischemia outside of the FAZ (once ischemic areas are treated once with grid FLT, these same areas should not be treated again).
  4. Laser will not be applied within the capillaries of the FAZ.

FLT will not be applied if any of the following apply and are identified:

  1. Significant macular ischemia involving the foveal avascular zone (once this has been determine additional fluorescein angiography for FLT planning should not be performed and subjects will not longer be eligible for rescue FLT).
  2. Treatment would be too close to the foveal avascular zone.
  3. Macular edema is not related to DME (eg: postoperative CME, etc).

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Retina Consultants of Houston/The Medical Center
      • Katy, Texas, United States, 77494
        • Retina Consultants of Houston/Katy office
      • The Woodlands, Texas, United States, 77384
        • Retina Consultants of Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A subject must meet the following criteria to be eligible for inclusion in the study:

    1. Enrolled and Completed VISTA DME (VGFT-OD-1009) clinical trial
    2. Willing and able to comply with clinic visits and study-related procedures
    3. Provide signed informed consent
    4. Enrollment in the trial within 12 weeks of trial activation.

Exclusion Criteria:

  • A subject who meets any of the following criteria will be excluded from the study:

    1. Prior treatment with anti-VEGF therapy in the study eye within 28 days of baseline
    2. Pregnant or breast-feeding women

    3. Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (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).

      • Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: PRN (pro re nata)
2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks
Drug: Aflibercept
pro re nata (PRN)
Other Names:
  • Eylea
Procedure: Focal Laser
Focal laser administered based on pre-specified criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Number of Intravitreal Aflibercept Injections for Subjects Who Were Enrolled and Completed the 3-year VISTA DME (VGFT-OD-1009) Trial
Time Frame: 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
Week 104

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity From Baseline to Week 52 and Baseline to Week 104
Time Frame: Week 52, Week 104
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.
Week 52, Week 104
Mean Number of Intravitreal Aflibercept Injections Before and After Receiving First Focal Laser Application.
Time Frame: Before First Focal Laser Treatment (FLT) at Week 12 or later; After First FLT at up to 104 weeks
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.
Before First Focal Laser Treatment (FLT) at Week 12 or later; After First FLT at up to 104 weeks
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
Time Frame: 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
Week 52, Week 104
Mean Change in Central Retinal Thickness From Baseline to Week 52 and Baseline to Week 104.
Time Frame: 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.
Week 52, Week 104
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.
Time Frame: 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.
Week 52, Week 104
Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy
Time Frame: Week 52, Week 104
Number of subjects with stable, worsened, or improved diabetic retinopathy through 104 weeks.
Week 52, Week 104
Number of Subjects That Receive Focal Laser Treatment.
Time Frame: Week 52, Week 104
Number of subjects that receive focal laser treatment from baseline to week 52 and from baseline to week 104.
Week 52, Week 104
Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Before and After Focal Laser Therapy
Time Frame: 104 weeks
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.
104 weeks
Mean Change in Central Retinal Thickness Before and After First Focal Laser Treatment
Time Frame: 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.
104 weeks
Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Past and Future Anti-VEGF Treatment Burden
Time Frame: Week 52, Week 104
Mean number of injections in 52 weeks and 104 weeks based on quantification of ischemic areas
Week 52, Week 104
Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Visual Outcomes
Time Frame: Week 52, Week 104
Mean change in visual acuity from baseline to week 52 and baseline to week 104 based on quantification of ischemic areas
Week 52, Week 104
Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Anatomic Outcomes
Time Frame: Week 52, Week 104
Mean change in central retinal thickness from baseline to week 52 based on quantification of ischemic areas
Week 52, Week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Greater Houston Retina Research

Collaborators

Regeneron Pharmaceuticals

Investigators

  • Principal Investigator: Charles C Wykoff, MD, Greater Houston Retina Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 24, 2014

Primary Completion (Actual)

January 9, 2017

Study Completion (Actual)

January 9, 2017

Study Registration Dates

First Submitted

October 15, 2014

First Submitted That Met QC Criteria

November 20, 2014

First Posted (Estimate)

November 24, 2014

Study Record Updates

Last Update Posted (Actual)

June 4, 2019

Last Update Submitted That Met QC Criteria

May 15, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • The Endurance 1 Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetic Macular Edema

Clinical Trials on Aflibercept

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe