ChemoCentryx, Inc., today announced that it reported positive Phase II results for CCX354 at the Annual Meeting of the American College of Rheumatology (ACR). CCX354 is an orally-active small molecule that specifically targets and inhibits the chemokine receptor known as CCR1, which is implicated in the development and progression of rheumatoid arthritis (RA). Results showed that CCX354 was safe and well tolerated by patients with RA in this clinical trial, and demonstrated clinical and biological activity at a dose of 200 mg once daily. These data were highlighted today in a late-breaker oral presentation in Chicago entitled "Safety and Efficacy of Oral Chemokine Receptor 1 Antagonist CCX354-C in a Phase II Rheumatoid Arthritis Study".
"The initial cloning and characterization of CCR1 as well as the chemokine known as RANTES, one of the main ligands for CCR1, was accomplished by the founder of ChemoCentryx over twenty years ago," stated Paul-Peter Tak, M.D., Ph.D., Lead Investigator and Professor at AMC/University of Amsterdam, currently also Senior Vice President/Head, Therapy Area ImmunoInflammation at GlaxoSmithKline. "Although there has been strong evidence implicating CCR1 in the pathology of RA, this is the first time that an investigational CCR1 antagonist has successfully demonstrated clinical efficacy in patients with this disease."
The results reported from this study, known as the CARAT-2 clinical trial, show that patients who met inclusion criteria at the start of dosing (Day 1 eligible) had an ACR20 response at Week 12 of 56% in patients receiving 200 mg CCX354 once daily compared to 44% in patients receiving 100 mg twice daily, and 30% in patients receiving placebo. The difference between 200 mg once daily and placebo was statistically significant (p=0.014). The decrease in CRP, a marker of inflammation, was statistically significant in the 200 mg QD group compared to placebo at Week 12 (p=0.023). ACR50, ACR70, DAS28-CRP, and ACR component results indicated greatest efficacy in the 200 mg daily dose group. Decreases in bone turnover markers C-telopeptide (CTx), procollagen type I N-terminal propeptide (PINP), and osteocalcin were more pronounced in the CCX354-C groups compared to placebo, and reaching statistically significant improvements at many time points during the study. Clinical responders had higher plasma CCX354 concentrations than non-responders. CCX354 was well tolerated by patients in this study.
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