AIMS: GSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in a first-in-human study to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model was employed to assess target engagement and the ability of the compound to inhibit recruitment of inflammatory CCR6 expressing cells. METHODS: This study was a randomized, double-blind (sponsor open), placebo-controlled, single-centre, single ascending intravenous dose escalation trial in 48 healthy male volunteers. RESULTS: GSK3050002 (0.1-20 mg kg-1 ) was well tolerated and no safety concerns were identified. The PK was linear over the dose range, with a half-life of approximately 2 weeks. Complex of GSK3050002/CCL20 increased in serum and blister fluid with increasing doses of GSK3050002. There were dose-dependent decreases in CCR6+ cell recruitment to skin blisters with maximal effects at doses of 5 mg kg-1 and higher, doses at which GSK3050002/CCL20 complex in serum and blister fluid also appeared to reach maximum levels. CONCLUSIONS: These results indicate a relationship between PK, target engagement and PD, suggesting a selective inhibition of recruitment of CCR6+ cells by GSK3050002 and support further development of GSK3050002 in autoimmune and inflammatory diseases.
RCT Entities:
AIMS: GSK3050002, a humanized IgG1κ antibody with high binding affinity to humanCCL20, was administered in a first-in-human study to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model was employed to assess target engagement and the ability of the compound to inhibit recruitment of inflammatory CCR6 expressing cells. METHODS: This study was a randomized, double-blind (sponsor open), placebo-controlled, single-centre, single ascending intravenous dose escalation trial in 48 healthy male volunteers. RESULTS:GSK3050002 (0.1-20 mg kg-1 ) was well tolerated and no safety concerns were identified. The PK was linear over the dose range, with a half-life of approximately 2 weeks. Complex of GSK3050002/CCL20 increased in serum and blister fluid with increasing doses of GSK3050002. There were dose-dependent decreases in CCR6+ cell recruitment to skin blisters with maximal effects at doses of 5 mg kg-1 and higher, doses at which GSK3050002/CCL20 complex in serum and blister fluid also appeared to reach maximum levels. CONCLUSIONS: These results indicate a relationship between PK, target engagement and PD, suggesting a selective inhibition of recruitment of CCR6+ cells by GSK3050002 and support further development of GSK3050002 in autoimmune and inflammatory diseases.
Authors: Kianoosh Katchar; Ciarán P Kelly; Sarah Keates; Michael J O'brien; Andrew C Keates Journal: Am J Physiol Gastrointest Liver Physiol Date: 2007-02-01 Impact factor: 4.052
Authors: Michael N Hedrick; Anke S Lonsdorf; Aiko-Konno Shirakawa; Chyi-Chia Richard Lee; Fang Liao; Satya P Singh; Hongwei H Zhang; Alexander Grinberg; Paul E Love; Sam T Hwang; Joshua M Farber Journal: J Clin Invest Date: 2009-08 Impact factor: 14.808
Authors: Jasper J Haringman; Danielle M Gerlag; Tom J M Smeets; Dominique Baeten; Filip van den Bosch; Barry Bresnihan; Ferdinand C Breedveld; Huib J Dinant; Francois Legay; Hermann Gram; Pius Loetscher; Robert Schmouder; Thasia Woodworth; Paul P Tak Journal: Arthritis Rheum Date: 2006-08
Authors: Lone Skov; Frank J Beurskens; Claus O C Zachariae; Sakari Reitamo; Jessica Teeling; David Satijn; Kim M Knudsen; Elmieke P J Boot; Debra Hudson; Ole Baadsgaard; Paul W H I Parren; Jan G J van de Winkel Journal: J Immunol Date: 2008-07-01 Impact factor: 5.422
Authors: Youmna Kfoury; Ninib Baryawno; Nicolas Severe; Shenglin Mei; Karin Gustafsson; Taghreed Hirz; Thomas Brouse; Elizabeth W Scadden; Anna A Igolkina; Konstantinos Kokkaliaris; Bryan D Choi; Nikolas Barkas; Mark A Randolph; John H Shin; Philip J Saylor; David T Scadden; David B Sykes; Peter V Kharchenko Journal: Cancer Cell Date: 2021-10-15 Impact factor: 31.743
Authors: Susan B Laffan; Andrew S Thomson; Shing Mai; Cindy Fishman; Takahito Kambara; Kiran Nistala; James T Raymond; Shugui Chen; Thulasi Ramani; Laura Pageon; Rodd Polsky; Mark Watkins; Gemma Ottolangui; John R White; Curtis Maier; Michael Herdman; Gerben Bouma Journal: PLoS One Date: 2020-04-23 Impact factor: 3.240
Authors: Line L Holm; Milica Vukmanovic-Stejic; Thomas Blauenfeldt; Thomas Benfield; Peter Andersen; Arne N Akbar; Morten Ruhwald Journal: J Vis Exp Date: 2018-08-11 Impact factor: 1.355