Xia Chen1, Qian Zhao1, Yong Hou1, Ji Jiang1, Wen Zhong1, Wenxiang Wang2, Xuejing Yao2, Lin Li2, Jianmin Fang3, Fengchun Zhang4, Pei Hu1. 1. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing. 2. RC Biotechnologies, Ltd., Yantai. 3. School of Life Science and Technology, Tongji University, Shanghai, China. 4. Department of Rheumatology, Peking Union Medical College Hospital, Beijing.
Abstract
AIM: RCT-18 is a recombinant fusion protein that interferes with the selection and survival of mature B-lymphocytes by inhibiting B-lymphocyte stimulator and a proliferation-inducing ligand. METHODS: This single blind, randomized, placebo controlled, clinical pharmacological study explored the short term efficacy and safety of RCT-18 in 21 rheumatoid arthritis (RA) patients with three different dosing regimens. The pharmacological behaviour of RCT-18 was also characterized through a six level biomarker cascade approach to identify potential predictors for clinical responses. RESULTS: Nine out of 10 patients (>80%) experienced moderate to good EULAR response at the end of 3 months with once or twice weekly doses of 180 mg RCT-18, whereas weekly administration of 360 mg RCT-18 or placebo, however, only resulted in moderate improvement in one patient in each group. Absence of IgM-type rheumatoid factor reduction, recovery of IgM 2 weeks after drug cessation, lack of decrease in the count of CD27(+) B-lymphocytes and a DAS28 change from baseline <6 in 4-6 weeks after the treatment initiation may indicate poor clinical response. No anti-drug antibody of RCT-18 was detected. The active treatments were well tolerated, although more mild to moderate infections were reported in patients receiving RCT-18. CONCLUSION: The study results support further development of RCT-18 in RA patients and provide important information for future dose selection.
RCT Entities:
AIM: RCT-18 is a recombinant fusion protein that interferes with the selection and survival of mature B-lymphocytes by inhibiting B-lymphocyte stimulator and a proliferation-inducing ligand. METHODS: This single blind, randomized, placebo controlled, clinical pharmacological study explored the short term efficacy and safety of RCT-18 in 21 rheumatoid arthritis (RA) patients with three different dosing regimens. The pharmacological behaviour of RCT-18 was also characterized through a six level biomarker cascade approach to identify potential predictors for clinical responses. RESULTS: Nine out of 10 patients (>80%) experienced moderate to good EULAR response at the end of 3 months with once or twice weekly doses of 180 mg RCT-18, whereas weekly administration of 360 mg RCT-18 or placebo, however, only resulted in moderate improvement in one patient in each group. Absence of IgM-type rheumatoid factor reduction, recovery of IgM 2 weeks after drug cessation, lack of decrease in the count of CD27(+) B-lymphocytes and a DAS28 change from baseline <6 in 4-6 weeks after the treatment initiation may indicate poor clinical response. No anti-drug antibody of RCT-18 was detected. The active treatments were well tolerated, although more mild to moderate infections were reported in patients receiving RCT-18. CONCLUSION: The study results support further development of RCT-18 in RApatients and provide important information for future dose selection.
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