Phase II Combination Steroid and Anti-VEGF for Persistent DME
Status:
Completed
Trial end date:
2017-06-05
Target enrollment:
Participant gender:
Summary
Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as
treatment for center-involved diabetic macular edema (DME), a substantial proportion of
anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of
retinal thickening. Indeed, over 50% of ranibizumab-treated eyes did not achieve a 2 or more
line improvement in visual acuity from baseline at 2 years in Protocol I, a previous DRCR.net
(Diabetic Retinopathy Clinical Research Network) study. Furthermore, 27% of
ranibizumab-treated eyes still had central subfield (CSF) thickness on time-domain optical
coherence tomography (OCT) ≥ 300 at 1 year, and more than 40% of ranibizumab-treated eyes did
not achieve complete resolution of retinal thickening (< 250 microns) by 2 years. Thus, there
is a need for alternative or additional treatments that will improve vision by reducing
retinal edema in eyes with persistent DME following previous anti-VEGF therapy. Intravitreal
steroid is not as efficacious as ranibizumab in eyes with DME overall, but it has been shown
to have a positive effect for DME in some eyes and might add benefit in eyes that are already
receiving anti-VEGF.
The main objective of this study is to assess the short-term effects of combination
steroid+anti-VEGF therapy on visual acuity and retinal thickness on OCT in comparison with
that of continued anti-VEGF therapy alone in eyes with persistent central-involved DME and
visual acuity impairment despite previous anti-VEGF treatment. This study will provide
important information for the design of a future confirmatory phase III clinical trial on the
efficacy of combination steroid and anti-VEGF in eyes with persistent DME and vision
impairment following previous anti-VEGF therapy. The primary outcome for efficacy will be the
mean change in visual acuity at 24 weeks.
Each study eye is required to complete a 12-week run-in phase. The run-in phase will identify
study eyes that truly have persistent DME despite anti-VEGF therapy by requiring an
additional 3 injections while also collecting standardized visual acuity and OCT
measurements. At the enrollment, 4-week and 8-week visits of the run-in phase, enrolled eyes
will receive an intravitreal injection of ranibizumab 3mg. Then at the 12-week run-in visit,
if the eye still has persistent DME, it will be randomized to receive either intravitreal
sham+intravitreal ranibizumab 0.3 or intravitreal dexamethasone+intravitreal ranibizumab 0.3
injections. The randomized study duration is 24 week, during which a protocol visit takes
place every month. The combination injections of sham+ranibizumab or dexamethasone
+ranibizumab will be given at the randomization visit (baseline) and at the 12-week visit
after randomization. In between, an intravitreal injection of ranibizumab only will be given
to study eyes at the 4, 8, 16 and 20 week visits.
Phase:
Phase 2
Details
Lead Sponsor:
Jaeb Center for Health Research
Collaborators:
Allergan Genentech, Inc. National Eye Institute (NEI)