Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial
- Paul P Tak1,
- Andra Balanescu2,
- Vira Tseluyko3,
- Silvia Bojin4,
- Edit Drescher5,
- Dan Dairaghi6,
- Shichang Miao6,
- Vittorio Marchesin6,
- Juan Jaen6,
- Thomas J Schall6,
- Pirow Bekker6
- 1Clinical Immunology and Rheumatology, F4-105, AMC/University of Amsterdam, Amsterdam, The Netherlands (currently also at GlaxoSmithKline, Stevenage, UK)
- 2Internal Medicine and Rheumatology, St Maria Hospital, Bucharest, Romania
- 3City Clinical Hospital, Kharkiv, Ukraine
- 4Spitalul Judetean de Urgenta ‘Dr Fogolyan Kristof’, Sf Gheorghe, Romania
- 5Veszprém Megyei Csolnoky Ferenc Kórház Nonprofit Zrt, Veszprém, Hungary
- 6ChemoCentryx, Inc, Mountain View, California, USA
- Correspondence to Paul P Tak, AMC/University of Amsterdam, Clinical Immunology and Rheumatology, F4-105, PO Box 22700, Amsterdam 1100 DD, Netherlands;
Contributors PPT: study design, enrollment and treatment of study subjects, data interpretation, writing. AB, VT, SB, ED: data interpretation, enrollment and treatment of study subjects, critical manuscript review. DD, SM, VM, JJ, TJS: data analysis, critical manuscript review. PB: study design, literature search, figures, data analysis, data interpretation, writing the paper.
- Accepted 31 March 2012
- Published Online First 15 May 2012
Objectives CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA).
Methods CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score–CRP, individual ACR components, as well as soluble bone turnover markers.
Results CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (−14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (−5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (−5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits.
Conclusions CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.
Collaborators The CARAT-2 Study Group. The investigators who contributed to CCR1 Antagonist Rheumatoid Arthritis Trial 2 (CARAT-2) are listed in the supplementary appendix, which is provided online only.
Competing interests PPT became an employee of GlaxoSmithKline after study completion. GSK has a proprietary interest in CCX354-C by virtue of an alliance with ChemoCentryx the sponsor company. ChemoCentryx and GSK funded the study.
Ethics approval Each study centre obtained ethics committee approval for the trial before the enrolment of any study subjects.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.