ChemoCentryx said CCX140, an orally active CCR2 antagonist, successfully met its primary endpoint of safety and tolerability and demonstrated clinical efficacy 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 only 28 days of treatment of CCX140.
"We are very pleased with the favorable results achieved by administering CCX140 in type 2 diabetic patients, since this is the population in which we plan to further evaluate the drug in a phase II trial in patients with diabetic nephropathy," said Thomas J. Schall, Ph.D., president and CEO of ChemoCentryx.
Results showed daily treatment with CCX140 was effective, safe and well tolerated. Additionally, daily treatment with CCX140 showed a dose-dependent decrease in fasting plasma glucose through week four. A significant decrease in HbA1c was observed after only four weeks of daily treatment of CCX140 (10mg) compared to placebo (p = 0.045). No detrimental effects were observed on plasma MCP-1 or blood monocyte levels, and once-daily oral CCX140 provided excellent plasma coverage.
This was a multi-national, 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 QD, 10 mg CCX140 QD, or open-label pioglitazone 30 mg QD for four 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).
CCX140 is chemically distinct from all other known antagonists of CCR2 and works by blocking the infiltration and activation of certain populations of monocyte/macrophages and other cells bearing CCR2 that occurs during inflammation, and thus is designed to provide selective treatment of the disease without compromising other immune functions.