Session Title: FP-15 Vascular Diseases and Diabetic Retinopathy V
Session Date/Time: Sunday 14/09/2014 | 08:00-10:00
Paper Time: 08:32
Venue: Boulevard D
First Author: : P.Hykin UK
Co Author(s): : H. Gerding F. Boscia R. Tadayoni S. Priglinger I. Pearce J. Mones
Retinal vein occlusion (RVO) is the second most common retinal vascular permeability disorder after diabetic retinopathy and is a leading cause of vision loss. Two phase III randomized double-masked 12-month controlled trials CRUISE (in central retinal vein occlusion [CRVO]) and BRAVO (in branch retinal vein occlusion) established the efficacy and safety of ranibizumab 0.5 mg in RVO. Based on these studies ranibizumab 0.5 mg was approved for the treatment of macular edema secondary to RVO in both the US and the European Union. Here, we describe the study design and baseline characteristics of patients enrolled in the CRYSTAL study (NCT01535261).
CRYSTAL is an ongoing 24 month phase IIIb open-label single-arm multicenter study designed to further evaluate the long term efficacy and safety of ranibizumab 0.5mg using an individualized visual acuity (VA) stabilization-driven pro re nata (PRN) dosing regimen in patients with visual impairment due to macular edema secondary to CRVO.
The study enrolled adults diagnosed with visual impairment exclusively due to macular edema secondary to CRVO and best-corrected-visual-acuity(BCVA) score between 73 and 19ETDRS letters(both inclusive) at screening and baseline. Patients using systemic anti-vascular endothelial growth factor (VEGF) drugs(<6 months prior to baseline) or previously treated with anti-angiogenic drugs(<3 months prior to baseline in either eye) were excluded. Enrolled patients received monthly ranibizumab 0.5mg intravitreal injections until VA was stable for 3 consecutive visits(Phase A). Thereafter patients were monitored monthly for VA and disease activity and re-entered Phase A upon signs of deterioration(based on treating physicians’ assessment). As of Month-12, the frequency of monitoring visits could be reduced to every 2-months for patients with stable VA and absence of disease activity. Key objectives/endpoints: to evaluate the efficacy of an individualized, stability-criteria-driven PRN dosing regimen of ranibizumab 0.5mg as assessed by the mean change in BCVA at Month-12 compared to baseline(primary endpoint), the mean and mean average change in BCVA and mean change in central subfield thickness from baseline through Month-12 and through Month-24 and safety over 24-months. Exploratory endpoints: to evaluate differences in treatment response between ischemic and non-ischemic patients and the influence of baseline BCVA on treatment outcomes.
A total of 356 patients with visual impairment due to macular edema secondary to CRVO were enrolled in the study from 78 sites in Europe, Australia and Canada. The mean age at baseline was 65.5 years and 64% of the patients were male. The study started in February 2012 and the last patient first visit (LPFV), occurred in April 2013 signifying that by April/May 2014 patients should have completed treatment period 1 (12-months) and reached the primary endpoint which will be subject to analysis and outcome results disclosure.
Baseline demographics such as age and gender are comparable to those observed in the pivotal CRUISE study. Additionally, spectral domain optical coherence tomography data collected in the study will provide further insights into predictive factors for disease progression and to evaluate the possibility of reduced monitoring. The long-term safety and efficacy data from this study will further guide the recommendations of ranibizumab treatment in CRVO.