title: Pharmacokinetics, Pharmacodynamics and Preliminary Observations for Clinical Activity and Safety of Multiple Doses of Human Mouse Chimeric Anti-CD22 Monoclonal Antibody (SM03) in Chinese Patients with Systemic Lupus Erythematosus.
abstract: OBJECTIVE
  SM03 is a novel recombinant, human/mouse chimeric immunoglobulin G1 monoclonal antibody directed against the CD22 antigen on human B lymphocytes. This was the first study to investigate the pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical activity of SM03 in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  This study was an open, multiple-centre, parallel-group, multiple-ascending-dose, phase I study in 29 SLE patients. Pharmacokinetic assessment was conducted in 22 of these patients. Eligible patients received multiple intravenous infusions of SM03 for 4 weeks (240 mg/m2, 600 or 900 mg, once weekly) and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety and clinical response.
  
  
  RESULTS
  After multiple-dose SM03, the maximal serum concentration of SM03 was reached within 3-7 h. The mean elimination half-life was 15 days. The average accumulation ratios of the area under the time-concentration curve and the maximum concentration after the fourth administration of SM03 were 2.0 and 1.5. CD19+B-lymphocyte counts were decreased. Infections were the most common adverse events. No drug-related serious adverse events were reported. The therapeutic benefit of SM03 was observed mainly in patients with moderate-to-severe disease activity.
  
  
  CONCLUSIONS
  Pharmacokinetic exposure increased in a lower-than-dose-proportional manner up to 900 mg. SM03 was well tolerated at doses ranging from 240 mg/m2to 900 mg, with no new safety signals identified. SM03 has potential efficacy in Chinese patients with SLE.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damucang, Xicheng District, Beijing, 100032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damucang, Xicheng District, Beijing, 100032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damucang, Xicheng District, Beijing, 100032, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Li
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damucang, Xicheng District, Beijing, 100032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: SinoMab BioScience, Ltd, BioIncubator No. 1-301, Science and Technology Park, Nanshan District, Shenzhen, 518057, Guangdong, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Li
authors.affiliation: SinoMab BioScience, Ltd, BioIncubator No. 1-301, Science and Technology Park, Nanshan District, Shenzhen, 518057, Guangdong, China. shawn@sinomab.com.
authors.forename: Shui-On
authors.initials: SO
authors.lastname: Leung
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. zhangfccra@aliyun.com.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damucang, Xicheng District, Beijing, 100032, China. pei.hu.pumc@gmail.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D005260:Female; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007262:Infusions, Intravenous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D051379:Mice; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C497867:CD22 protein, human; D007074:Immunoglobulin G; D051918:Sialic Acid Binding Ig-like Lectin 2