{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:46Z","timestamp":1787026486714,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>\u00ae<\/jats:sup>\n                      version 9.2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WBP216 demonstrated a good safety profile and evidence of potential efficacy in the treatment of patients with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>http:\/\/www.chinadrugtrials.org.cn\/clinicaltrials.searchlistdetail.dhtml<\/jats:uri>\n                      , identifier CTR20170306.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.1110992","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T11:58:25Z","timestamp":1678103905000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["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"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaomei","family":"Leng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiange","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoduo","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cipo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21659","article-title":"Updated recommendations for the treatment of rheumatoid arthritis: Another step on a long road","volume":"64","author":"Daikh","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21641","article-title":"2012 Update of the 2008 American college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis","volume":"64","author":"Singh","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"CD008794","DOI":"10.1002\/14651858.CD008794.pub2","article-title":"Adverse effects of biologics: A network meta-analysis and cochrane overview","volume":"2","author":"Singh","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61704-9","article-title":"Risk of serious infection in biological treatment of patients with rheumatoid arthritis: A systematic review and meta-analysis","volume":"386","author":"Singh","year":"2015","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"E5238","DOI":"10.3390\/ijms21155238","article-title":"Interleukin-6 in rheumatoid arthritis","volume":"21","author":"Pandolfi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2009.04.018","article-title":"Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production","volume":"17","author":"Hashizume","year":"2009","journal-title":"Osteoarthritis Cartilage"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.03.017","article-title":"IL-6 and IL-1 synergistically enhanced the production of MMPs from synovial cells by up-regulating IL-6 production and IL-1 receptor I expression","volume":"51","author":"Suzuki","year":"2010","journal-title":"Cytokine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.8.5.669","article-title":"The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis","volume":"8","author":"Ohsugi","year":"2008","journal-title":"Expert Opin Biol Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp070449","article-title":"Tocilizumab: the first interleukin-6-receptor inhibitor","volume":"65","author":"Sebba","year":"2008","journal-title":"Am J Health Syst Pharm"},{"key":"B14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4137\/CMAMD.S7371","article-title":"Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis","volume":"5","author":"Ogata","year":"2012","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"B15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1177\/2040622312466908","article-title":"Tocilizumab in rheumatoid arthritis: Efficacy, safety and its place in therapy","volume":"4","author":"Kaneko","year":"2013","journal-title":"Ther Adv Chronic Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210310","article-title":"Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): A randomised, double-blind, parallel-group phase III trial","volume":"76","author":"Burmester","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4137\/CMAMD.S4864","article-title":"Tocilizumab: a review of its safety and efficacy in rheumatoid arthritis","volume":"3","author":"Jones","year":"2010","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key361","article-title":"Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis","volume":"58","author":"Emery","year":"2019","journal-title":"Rheumatol (Oxf)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.617265","article-title":"Modeling and simulation to support phase Ib\/IIa dose selection for WBP216, a long half-life fully human monoclonal antibody against interleukin-6","volume":"12","author":"Tang","year":"2021","journal-title":"Front Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604292200","article-title":"Properties of human IgG1s engineered for enhanced binding to the neonatal fc receptor (FcRn)","volume":"281","author":"Dall\u2019Acqua","year":"2006","journal-title":"J Biol Chem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes279","article-title":"ACR\/EULAR 2010 rheumatoid arthritis classification criteria","author":"Kay","year":"2012","journal-title":"Rheumatol (Oxford)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602","article-title":"American College of rheumatology. preliminary definition of improvement in rheumatoid arthritis","volume":"38","author":"Felson","year":"1995","journal-title":"Arthritis Rheum"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K","article-title":"Validation of rheumatoid arthritis improvement criteria that include simplified joint counts","volume":"41","author":"van Gestel","year":"1998","journal-title":"Arthritis Rheum"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3899\/jrheum.130466","article-title":"Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan","volume":"41","author":"Koike","year":"2014","journal-title":"J Rheumatol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1136\/annrheumdis-2015-207281","article-title":"Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA)","volume":"75","author":"Burmester","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/rheumatology\/kex443","article-title":"Subcutaneous tocilizumab in rheumatoid arthritis: Findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries","volume":"57","author":"Choy","year":"2018","journal-title":"Rheumatol (Oxf)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.5414\/CP201819","article-title":"Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, following single-dose administration by subcutaneous and intravenous routes to healthy subjects","volume":"51","author":"Zhang","year":"2013","journal-title":"Int J Clin Pharmacol Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.5414\/CP201904","article-title":"Pharmacokinetics and pharmacodynamics of tocilizumab after subcutaneous administration in patients with rheumatoid arthritis","volume":"51","author":"Zhang","year":"2013","journal-title":"Int J Clin Pharmacol Ther"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev277","article-title":"Immunogenicity of biologic agents in rheumatoid arthritis patients: Lessons for clinical practice","volume":"55","author":"Schaeverbeke","year":"2016","journal-title":"Rheumatol (Oxf)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jbspin.2016.04.013","article-title":"Immunogenicity of tocilizumab in patients with rheumatoid arthritis","volume":"84","author":"Sigaux","year":"2017","journal-title":"Joint Bone Spine"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1110992\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T11:58:27Z","timestamp":1678103907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1110992\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,28]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2022.1110992"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1110992","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,28]]},"article-number":"1110992"}}