Abstract
Purpose: :
To summarize key findings of the LUMINATE (LX211 Uveitis Multicenter Investigation of a New Approach to Treatment) development program for noninfectious uveitis of the posterior segment (intermediate, anterior and intermediate, posterior, or panuveitis)
Methods: :
LX211 (voclosporin) is a novel, calcineurin phosphatase inhibitor and potent immunosuppressive agent. The LUMINATE development program comprises three dose-ranging, double-masked, placebo-controlled studies totaling 558 subjects. Two were conducted in the target population, ie, subjects with noninfectious uveitis in the posterior segment: LX211-01 (active uveitis), LX211-02 (controlled uveitis) and one in anterior uveitis (LX211-03) used primarily for safety. For the 01 study co-primary efficacy endpoints, based on the SUN Working Group 6-point scale for VH assessment, were mean change from baseline in vitreous haze (VH) in the study eye at 16 and 24 weeks, or at time of rescue, if earlier. The primary endpoint in the 02 study was the proportion of subjects with an inflammatory exacerbation, ie, VH or anterior chamber cells increase of 2 or more grades from baseline or visual acuity change from baseline of 15 ETDRS letters. In both studies immunosuppressive agents were discontinued prior to randomization; standardized tapering of topical and systemic corticosteroids ensured interpretability of results.
Results: :
In the 01 study there was a statistically significant difference for the co-primary endpoints for LX211 0.4 mg/kg compared with control: week 16 (p=0.008) and week 24 (p=0.027). Time to rescue in the LX211 group was nearly 2-fold compared with the control group. In the 02 study 0.4mg/kg LX211 reduced the rate of recurrence of inflammatory exacerbation up to 50% over 26 weeks of treatment. The safety profile is consistent with this class of drugs.
Conclusions: :
Results from the 01 study at weeks 16 and 24 demonstrate and initial and persistent treatment effect with a clinically meaningful reduction in VH. Results from the 02 study support the efficacy of LX211 on active uveitis and suggest control of inflammation for those on LX211 compared with control. The safety of LX211 is manageable with routine monitoring.
Clinical Trial: :
http://www.clinicaltrials.gov NCT00404742