Qian Zhao1, Xia Chen1, Jing Li2, Ji Jiang1, Mengtao Li2, Wen Zhong1, Zhengdong Li3, Shui-On Leung4, Fengchun Zhang5, Pei Hu6. 1. 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. 2. Department of Rheumatology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. 3. SinoMab BioScience, Ltd, BioIncubator No. 1-301, Science and Technology Park, Nanshan District, Shenzhen, 518057, Guangdong, China. 4. SinoMab BioScience, Ltd, BioIncubator No. 1-301, Science and Technology Park, Nanshan District, Shenzhen, 518057, Guangdong, China. shawn@sinomab.com. 5. Department of Rheumatology, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. zhangfccra@aliyun.com. 6. 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.
Abstract
BACKGROUND AND OBJECTIVES: 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. CONCLUSION: Pharmacokinetic exposure increased in a lower-than-dose-proportional manner up to 900 mg. SM03 was well tolerated at doses ranging from 240 mg/m2 to 900 mg, with no new safety signals identified. SM03 has potential efficacy in Chinese patients with SLE.
BACKGROUND AND OBJECTIVES: 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. CONCLUSION: Pharmacokinetic exposure increased in a lower-than-dose-proportional manner up to 900 mg. SM03 was well tolerated at doses ranging from 240 mg/m2 to 900 mg, with no new safety signals identified. SM03 has potential efficacy in Chinese patients with SLE.
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