PMID- 36926529 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20230327 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of WBP216, a novel IL-6 monoclonal antibody, in patients with rheumatoid arthritis: A phase Ia randomized placebo-controlled study. PG - 1110992 LID - 10.3389/fimmu.2022.1110992 [doi] LID - 1110992 AB - BACKGROUND: WBP216 is a novel human immunoglobulin G1 (IgG1) monoclonal antibody for interleukin (IL)-6. We aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single ascending dose (SAD) of WBP216 in patients with rheumatoid arthritis (RA). METHODS: In this double-blind, placebo-controlled, SAD, phase Ia study, patients with RA were randomized in a 3:1 (Group A1, 10 mg) and 6:2 (Group A2, 30 mg; Group A3, 75 mg; Group A4, 150 mg; Group A5, 300 mg) ratios to receive either ascending doses of WBP216 or placebo subcutaneously. The primary endpoint was the incidence of adverse events (AEs), while the secondary endpoints were characterization of PK, PD, and immunogenicity of WBP216 and the exploratory endpoints included improvements in RA clinical metrics. All statistical analyses were performed using SAS((R)) version 9.2. RESULTS: A total of 41 subjects (34 females and 7 males) were enrolled in the study. WBP216 was well tolerated in all doses (10-300 mg). Most treatment-emergent AEs (TEAEs; 97.6%) were of grade 1 severity and resolved without any treatment. No subjects experienced TEAEs leading to withdrawal or death during the study. An increase in serum concentration and total IL-6 from baseline was observed, while a substantial decrease in high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) was observed in all the WBP216 groups. Anti-drug antibodies were detected in only one subject after dosing, indicating an acceptable immunogenicity profile. Limited ACR20 and ACR50 response was observed in the WBP216 groups and no response in the placebo group. CONCLUSION: WBP216 demonstrated a good safety profile and evidence of potential efficacy in the treatment of patients with RA. CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20170306. CI - Copyright (c) 2023 Leng, Tang, Hu, Guan, Li, Huang, Zhang, Chen and Zeng. FAU - Leng, Xiaomei AU - Leng X AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. FAU - Tang, Xiange AU - Tang X AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Hu, Pei AU - Hu P AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Guan, Xiaoduo AU - Guan X AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Li, Qian AU - Li Q AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Huang, Cipo AU - Huang C AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Zhang, Qiang AU - Zhang Q AD - WuXi Clinical Development Services Co., Ltd, Wuxi, China. FAU - Chen, Rui AU - Chen R AD - Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. FAU - Zeng, Xiaofeng AU - Zeng X AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230228 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Monoclonal) RN - 0 (Interleukin-6) RN - 0 (Antirheumatic Agents) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Male MH - Female MH - Humans MH - Antibodies, Monoclonal/adverse effects MH - Interleukin-6 MH - *Antirheumatic Agents/adverse effects MH - Antibodies, Monoclonal, Humanized/adverse effects MH - *Arthritis, Rheumatoid PMC - PMC10011485 OTO - NOTNLM OT - WBP216 OT - monoclonal antibody OT - placebo-controlled OT - rheumatoid arthritis OT - safety COIS- QZ was employed by WuXi Clinical Development Services Co., Ltd. The authors declare that this study received funding from WuXi-MedImmune (WuXi-AZ). The funder WuXi-AZ was involved in the study design, collection, analysis, and processing of data. EDAT- 2023/03/18 06:00 MHDA- 2023/03/21 06:00 PMCR- 2022/01/01 CRDT- 2023/03/17 02:52 PHST- 2022/11/29 00:00 [received] PHST- 2022/12/26 00:00 [accepted] PHST- 2023/03/17 02:52 [entrez] PHST- 2023/03/18 06:00 [pubmed] PHST- 2023/03/21 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1110992 [doi] PST - epublish SO - Front Immunol. 2023 Feb 28;13:1110992. doi: 10.3389/fimmu.2022.1110992. eCollection 2022.