Abstract: INFO08-SA
LUMINA-1: A Randomized, Controlled, Dose-Ranging Study in Patients with Focal Segmental Glomerulosclerosis Treated with CCX140, an Inhibitor of the Chemokine Receptor CCR2
Session Information
- Informational Posters - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Cortazar, Frank B., Massachusetts General Hospital, Watertown, Massachusetts, United States
- Niles, John, Massachusetts General Hospital, Watertown, Massachusetts, United States
- Bekker, Petrus, Chemocentryx Inc., Mountain View, California, United States
- Singh, Rajinder, Chemocentryx Inc., Mountain View, California, United States
- Zhao, Bin N., Chemocentryx Inc., Mountain View, California, United States
- Miao, Zhenhua, Chemocentryx Inc., Mountain View, California, United States
- Schall, Thomas J., Chemocentryx Inc., Mountain View, California, United States
- Staehr, Peter, Chemocentryx Inc., Mountain View, California, United States
Description
Background: Primary Focal Segmental Glomerulosclerosis (FSGS) is a histologic lesion associated with the nephrotic syndrome and a common feature in end-stage renal disease. There are no approved therapies for primary FSGS, but current regimens comprise renin-angiotensin-aldosterone (RAAS) inhibitors administered with glucocorticoids and other immunosuppressants to reduce proteinuria and calcineurin inhibitors with cytotoxic agents in cases complicated by steroid dependence or resistance. A role for the chemokine receptor CCR2 in primary FSGS is supported by the following observations: 1) Rapid improvement in proteinuria and glomerulosclerosis with pharmacologic inhibition or genetic deletion of CCR2 in mice with adriamycin nephropathy or 5/6 nephrectomy; 2) Increased podocyte density and integrity with CCR2 inhibition; 3) Significant increase in expression of CCR2 and its signature ligand CCL2 in FSGS patients; and 4) Rapid and durable reduction in proteinuria with CCR2 inhibitor therapy (CCX140) in human CKD. These findings provide the rationale for investigating CCR2 inhibitor therapy in human primary FSGS.
Methods: LUMINA-1 is a Phase 2 randomized and double blinded trial enrolling ~40 patients with biopsy- or genetically-proven primary FSGS. Patients at entry have an eGFR >30 mL/min/1.73m2, urine protein-to-creatinine ratio (UPCR) ≥1 g protein/g creatinine, and stable background therapy (e.g., glucocorticoids, immunosuppressants, calcineurin inhibitors, or RAAS inhibitors). Patients are randomized 1:1:1:1 to receive one of three doses of CCX140 or placebo for 12 wks, followed by 12 weeks of CCX140 open label. Stratification is by UPCR and by concomitant background therapy. The primary endpoint is change from baseline in UPCR at 12 wks; secondary endpoints include changes from baseline in total proteinuria and eGFR at 12 and 24 wks.
Conclusion: The LUMINA-1 trial will provide data on the potential safety and efficacy of CCX140 in reducing proteinuria and improving renal function in FSGS patients.
Funding
- ChemoCentryx Inc.