ChemoCentryx has initiatied a phase II clinical trial for CCX140, an orally-administered small molecule for the treatment of diabetic kidney disease (diabetic nephropathy). CCX140 is a novel CCR2 inhibitor with a pharmacological profile unlike that of other CCR2 compounds that have been known to be tested by other sponsors. CCX140 works by blocking the infiltration and activation of certain populations of monocyte and macrophages and other cells bearing CCR2 that occurs during inflammation. This mechanism of action provides selective treatment of the disease without compromising other immune functions.
As a precursor to the recently initiated clinical trials for CCX140 in patients with diabetic nephropathy, in an earlier phase II clinical trial, ChemoCentryx assessed the safety, tolerability and clinical effects of CCX140 in type 2 diabetics with normal kidney function. In that trial, CCX140 demonstrated clinical efficacy and successfully met its primary endpoint of safety and tolerability in type 2 diabetics on stable doses of metformin. Specifically, a statistically significant decrease in hemoglobin A1c (HbA1c) relative to placebo and a dose-dependent lowering of fasting plasma glucose were shown following only 28 days of treatment with CCX140. Additionally, ChemoCentryx's CCR2 inhibitors have shown to significantly improve kidney function and hyperglycemia in preclinical models of diabetic nephropathy in addition to those for type 2 diabetes.
The randomized, double-blind placebo controlled phase II study is designed
to evaluate the safety and tolerability of CCX140 in subjects with diabetic nephropathy. Other objectives are to study the efficacy of CCX140 versus placebo in changes from baseline in urinary albumin to creatinine ratio (ACR) and HbA1c. The trial is expected to enroll at least 135 subjects randomized to one of three treatment groups: placebo, 5 mg or 10 mg CCX140 once daily for a treatment duration of 12 weeks with a four-week follow-up period. Following an interim analysis for efficacy evaluation, the sample size may be increased to up to 270 patients, and/or dose groups may be added.