Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Methods: 7 sequential cohorts consisting of any race (cohorts A to D) and non-Asian (cohorts E to G) received single increasing doses of IV administered ASP5094 or placebo. Serial Cohorts A and B consisted of 6 subjects each (4 active and 2 placebo) while cohorts C to G consisted of 8 subjects each (6 active and 2 placebo). Serial blood samples were collected for PK (ASP5094 and anti-ASP5094) and PD (alpha-9- integrin receptor occupancy (RO)).
Results: Following a 30-minute infusion of ASP5094 at doses <0.25 mg/kg most serum ASP5094 concentrations fell below the limit of detection (10 ng/mL). At doses that ranged from 0.25-10 mg/kg, mean maximum ASP5094 serum concentrations (Cmax) increased nonlinearly with dose and ranged from 4742 to 277365 ng/mL. Similarly, mean ASP5094 AUC0-infalso increased nonlinearly from 165,455 to 77,829,650 ng*h/mL with ASP5094 doses ranging from 0.25 to 10 mg/kg. ASP5094 PK exhibited nonlinear target-mediated drug disposition. Alpha-9 receptor occupancy (RO) on neutrophils remained at 100% for periods of 1, 2, 4 and 8 weeks following a single IV administration at doses of 0.25, 1, 3 and 10 mg/kg ASP5094 respectively. A direct response relationship was observed between serum ASP5094 exposure and RO. One subject dosed at 0.25 mg/kg with ASP5094 tested positive for anti-drug antibodies (ADA) on Day 90 and remained positive throughout study. The last study visit was Day 360. Drug-related adverse events (AE) were reported in 16.7% of the 0.25 mg/kg dose cohort; 33.3% of the 1 mg/kg cohort; 50% of the 3 mg/kg cohort; and 16.7% of the 10 mg/kg cohort, with no dose-dependency. There were no clinically significant abnormal ECG findings in this study.
To cite this abstract in AMA style:Wang T, Lademacher C, Blahunka P, Howieson C, Yang T, Wojtkowski T, Kikuchi M, Townsend R. Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of ASP5094, an Anti-Alpha-9-Integrin Monoclonal Antibody, Following Single Intravenous Doses in Healthy Subjects [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pharmacokinetics-pk-pharmacodynamics-pd-and-safety-of-asp5094-an-anti-alpha-9-integrin-monoclonal-antibody-following-single-intravenous-doses-in-healthy-subjects/. Accessed March 26, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetics-pk-pharmacodynamics-pd-and-safety-of-asp5094-an-anti-alpha-9-integrin-monoclonal-antibody-following-single-intravenous-doses-in-healthy-subjects/