Abstract
Purpose: :
Ranibizumab (LUCENTIS®) is a humanized IgG1 antibody fragment that inhibits biologic activity of human vascular endothelial growth factor A (VEGF-A) and is FDA-approved for patients with neovascular age-related macular degeneration. We herein describe RIDE and RISE, two phase III, multicenter, sham injection-controlled trials to evaluate the efficacy and safety of intravitreal ranibizumab in macular edema with center involvement secondary to diabetes mellitus.
Methods: :
Each trial is enrolling ~366 men and women ≥18 years of age with retinal thickening secondary to type 1 or 2 diabetes. Eligible subjects have 20/40-20/320 best-corrected visual acuity (BCVA) in the study eye and decreases in visual acuity that are primarily due to diabetic macular edema (DME). Exclusion criteria include DME without center involvement, vitreomacular traction, additional macular pathology, proliferative diabetic retinopathy, and macular laser treatment or intravitreal therapy with anti-VEGF or corticosteroids within 3 months prior to study onset. Subjects will be randomized to intravitreal ranibizumab or sham injection groups at ~100 sites in the United States, South America, Latin America, and South Africa. The primary efficacy outcome measure is the proportion of subjects who gain ≥15 letters in BCVA compared to baseline at 24 months. Secondary outcome measures include changes from baseline in BCVA, foveal thickness, National Eye Institute Visual Functioning Questionnaire-25 near- and distance-activities subscale scores, and contrast sensitivity; the proportion of subjects with resolved leakage; and the number of macular laser treatments. Safety will be assessed by monitoring and recording protocol-defined adverse events, serious adverse events, and protocol-specified laboratory analyses.
Results: :
RIDE and RISE studies are currently enrolling subjects.
Conclusions: :
Unmet therapeutic needs drive the demand for new DME treatments. Clinical rationale for ranibizumab inhibition of VEGF-A in the treatment of DME will be discussed.
Clinical Trial: :
www.clinicaltrials.gov NCT00473382
Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • diabetic retinopathy • vascular endothelial growth factor