A Randomized Controlled Trial of the Efficacy and Safety of CCX282-B, an Orally-Administered Blocker of Chemokine Receptor CCR9, for Patients with Crohn's Disease

被引：120

作者：

Keshav, Satish ^{[1
]}

Vanasek, Tomas ^{[2
]}

Niv, Yaron ^{[3
]}

Petryka, Robert ^{[4
]}

Howaldt, Stephanie

Bafutto, Mauro ^{[5
]}

Racz, Istvan ^{[6
]}

Hetzel, David ^{[7
]}

Nielsen, Ole Haagen ^{[8
]}

Vermeire, Severine ^{[9
]}

Reinisch, Walter ^{[10
]}

Karlen, Per ^{[11
]}

Schreiber, Stefan ^{[12
]}

Schall, Thomas J. ^{[13
]}

Bekker, Pirow ^{[13
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England

[2] Hepatogastroenterol HK, Hradec Kralove, Czech Republic

[3] Rabin Med Ctr, Petah Tiqwa, Israel

[4] NZOZ Vivamed, Zespol Lekarzy Specjalistow, Warsaw, Poland

[5] Inst Goiano Gastroenterol & Endoscopia Digest Ltd, Goiania, Go, Brazil

[6] Petz Aladar Cty & Teaching Hosp, Gyor, Hungary

[7] Royal Adelaide Hosp, Adelaide, SA 5000, Australia

[8] Herlev Hosp, Dept Gastroenterol, DK-2730 Herlev, Denmark

[9] Univ Hosp Gasthuisberg, Louvain, Belgium

[10] Allgemeines Krankenhaus Wien, Univ Klin Innere Med 3, Klin Abt Gastroenterol & Hepatol, Vienna, Austria

[11] Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden

[12] Univ Kiel, Dept Med 1, Univ Hosp Schleswig Holstein, Kiel, Germany

[13] ChemoCentryx Inc, Mountain View, CA 94043 USA

来源：

PLOS ONE | 2013年 / 8卷 / 03期

关键词：

THYMUS-EXPRESSED CHEMOKINE; LYMPHOCYTES; LOCALIZATION; NATALIZUMAB; THERAPY; INDEX; CELLS;

D O I：

10.1371/journal.pone.0060094

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a >= 70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease.

引用

页数：12

共 21 条

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