ChemoCentryx has reported that its novel, orally active CCR2 antagonist, CCX140-B, demonstrated an excellent safety profile and exhibited clear signs of biological and clinical effect in a phase II study in patients with type 2 diabetes on stable doses of metformin. 

While demonstrating safety and tolerability, a statistically significant decrease in hemoglobin A1c (HbA1c) relative to placebo and a dose-dependent lowering of fasting plasma glucose were shown following 28 days of treatment with CCX140-B. Additionally, the company reported that CCR2 antagonism significantly improves kidney function and hyperglycemia in preclinical models of type 2 diabetes.  These combined results indicate that CCX140-B may be effective in the treatment of renal disease resulting from complications associated with diabetes.  CCX140-B is in position to enter phase II clinical development for the treatment of diabetic nephropathy in the fourth quarter of 2011.

Results showed that daily treatment with CCX140-B was effective, safe and well tolerated.  Additionally, treatment with CCX140-B showed a dose-dependent decrease in fasting glucose through week 4.  A significant decrease in HbA1c was observed after only 4 weeks of daily treatment of CCX140-B (10 mg) compared to placebo. No detrimental effects were observed on plasma MCP-1 or blood monocyte levels, and once daily oral CCX140-B provided excellent plasma coverage.

This was a multinational, randomized, double-blind, placebo and active-controlled clinical trial in 159 patients with type 2 diabetes on stable doses of metformin.  HbA1c was 6.5 to 10% and fasting plasma glucose 135 to 270 mg/dL at study entry.  Randomized subjects received double-blind placebo QD, 5 mg CCX140-B QD, 10 mg CCX140-B QD, or open label pioglitazone hydrochloride 30 mg for 4 weeks.  The average age was 59 years and 64% of the participants were male.  Mean body mass index was 32 kg/m2 and diabetes duration was 5.8 years (median).