Multiple studies have implicated vascular endothelial growth factor VEGF as a major causative
factor in human eye diseases characterized by neovascularization including proliferative
diabetic retinopathy (PDR) and vascular permeability including diabetic macular edema (DME).
While there is strong evidence that PDR outcomes are markedly reduced in eyes that are
treated with monthly anti-VEGF therapy (A Study of Ranibizumab Injection in Subjects With
Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes
Mellitus: RIDE/RISE) and moderately reduced in eyes that received fairly frequent dosing
during the 1st year of treatment (Diabetic Retinopathy Clinical Research Network protocol I),
it is unknown whether or not an earlier but less frequent dosing regimen would result in
similar, favorable anatomic outcomes, and whether favorable anatomic outcomes subsequently
would result in favorable visual acuity outcomes.
If this study demonstrates that intravitreous aflibercept treatment is effective and safe for
reducing the onset of PDR or center involved- DME (CI-DME) in eyes that are at high risk for
these complications, a new strategy to prevent vision threatening complications of diabetes
will be available for patients. The application of intravitreous aflibercept earlier in the
course of disease (i.e., at the time when an eye has baseline severe non-proliferative
diabetic retinopathy) could help to reduce future potential treatment burden in patients, at
the same time resulting in similar or better long-term visual outcomes, if PDR and DME are
prevented.
The primary objectives of this protocol are to 1) determine the efficacy and safety of
intravitreous aflibercept injections versus sham injections (observation) for prevention of
PDR or CI-DME in eyes at high risk for development of these complications and 2) compare
long-term visual outcomes in eyes that receive anti-VEGF therapy early in the course of
disease with those that are observed initially, and treated only if high-risk PDR or CI-DME
with vision loss develops.
Secondary objectives include:
- Comparing other visual acuity outcomes between treatment groups, such as proportion of
eyes with at least 10 or at least 15 letter loss from baseline, or gain or loss of at
least 5 letters at the consecutive study visit just before and at the 2- or 4-year visit
- Comparing optical coherence tomography (OCT) outcomes, such as mean change in OCT
central subfield thickness and volume from baseline
- Comparing proportion of eyes with at least 2 and 3-step worsening or improvement of
diabetic retinopathy severity level (scale for individual eyes) by central reading
center from baseline
- Comparing associated treatment and follow-up exam costs between treatment groups
- Comparing safety outcomes between treatment groups
Phase:
Phase 3
Details
Lead Sponsor:
Jaeb Center for Health Research
Collaborators:
Juvenile Diabetes Research Foundation National Eye Institute (NEI) National Institutes of Health (NIH) Regeneron Pharmaceuticals