Chemocentryx and Vifor Fresenius Medical Care Renal Pharma (VFMCRP) announced topline data from the Phase II LUMINA-1 trial evaluating CCX140 for the treatment of the orphan kidney disorder, primary Focal Segmental Glomerulosclerosis (FSGS). In the study, CCX140 did not reach the primary endpoint of demonstrating a meaningful reduction in proteinuria relative to the control group after 12 weeks of blinded treatment.
LUMINA-1 was a multi-center, randomized, double-blind, placebo-controlled dose-ranging study designed to evaluate the safety and efficacy of CCX140 in patients primary FSGS with ≥1 gram/day baseline proteinuria (protein in the urine). The study enrolled a total of 46 patients worldwide, randomizing them to one of four arms (1:1:1:1). Patients received a placebo or CCX140 dosed at 5 mg once-daily, 10 mg twice daily, or 15mg twice-daily over 12 weeks. After the 12-week randomization period, all patients were eligible for an additional 12 weeks of CCX140 treatment in an open-label extension (OLE) with the highest safe dose of CCX140, which was 15mg twice-daily.
The primary efficacy measure was a change in proteinuria (measured by urine protein to creatinine ratio, (UPCR)) in the four blinded treatment groups from baseline to week 12. At week 12, all subjects including those in the placebo group were then treated with the highest dose of CCX140, 15 mg twice-daily (BID) for an additional 12 weeks of treatment, after which UPCR changes from week 12 to week 24 were also assessed. In the intent to treat (ITT) analysis of UPCR changes at week 12 relative to baseline, the 15 mg BID CCX140 group exhibited the greatest reduction of UPCR (median reduction from baseline 0.9 g/g or approximately 30%, and approximately 25% reduction from baseline for the geometric mean), but that did not differ significantly from the placebo group (median reduction from baseline 0.45 g/g; or approximately 22%, and approximately 23% reduction from baseline for the geometric mean). CX140 at all doses was well-tolerated, with no serious adverse events (SAEs) during the blinded trial and a numerically lower rate of treatment-emergent adverse events in the CCX140 treatment groups than in the placebo group.
A full analysis of the LUMINA-1 data is underway and expanded results are expected to be announced at a medical meeting later this year.
CCX140 is an orally-administered inhibitor of the chemokine receptor known as CCR2, which has been identified as a main driver of inflammatory monocyte and macrophage recruitment into diseased kidneys. The U.S. Food and Drug Administration has granted CCX140 orphan-drug designation for the treatment of FSGS.
About Focal Segmental Glomerulosclerosis
FSGS is a rare form of chronic disease kidney that affects approximately 80,000 patients in the U.S. and Europe, with 5,500-9,500 new cases each year. FSGS attacks the kidney’s filtering units (glomeruli) causing serious scarring which leads to permanent kidney damage. Progressive FSGS can lead to end-stage renal disease, ultimately requiring kidney transplant or renal dialysis. Currently there are no FDA approved treatments for FSGS.