This study is to determine danirixin (GSK1325756) concentrations required to inhibit neutrophil activation in blood obtained from Respiratory Syncytial Virus (RSV)-infected children \<2 years and healthy adults. The study will evaluate differences in neutrophil activation between RSV-infected children \<2 years and healthy adults with escalating concentrations of Chemokine (C-X-C motif) Ligand 1 (CXCL1) and danirixin to determine if RSV-infected children and adult neutrophils are similarly activated by CXCL1 and inhibited by danirixin. This study will guide dose prediction to inhibit specific percentages of neutrophils in future pediatric RSV-infection studies. This single-center, in vitro study will consist of 2 parts. Approximately 24 subjects will be enrolled, including 12 healthy adults and 12 RSV-infected children \<2 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
40
Powdered form for in-vitro administration to blood sample
Escalating concentrations of CXCL1 will be added to whole blood in vitro. A CXCL1/CD11b upregulation concentration response curve will determine the concentration to be used in Part 2.
GSK Investigational Site
Syracuse, New York, United States
Percent inhibition of Chemokine Ligand (CXCL1)-induced Cluster of Differentiation 11b expression on peripheral blood neutrophils in RSV-infected children <2 years and healthy adults after in vitro incubation with escalating concentrations of danirixin
Blood (1.5 milliliter \[mL\]) will be collected from a peripheral vein via indwelling catheter or direct venepuncture. Escalating concentrations of danirixin (0.03-100 micromoles) will be added to whole blood in vitro with a fixed concentration of CXCL1 to determine inhibition of Cluster of Differentiation 11b (CD11b) expression on peripheral blood neutrophils analyzed by Fluorescence-Activated Cell sorting (FACs).
Time frame: Day 1
CD11b upregulation on peripheral blood neutrophils in RSV-infected children <2 years and healthy adults after in vitro incubation with escalating concentrations of CXCL1
Blood (1.0 mL) will be collected from a peripheral vein via indwelling catheter or direct venepuncture. Escalating concentrations of CXCL1 will be added to whole blood in vitro and CD11b upregulation on peripheral blood neutrophils will be analyzed by FACS
Time frame: Day 1
Differences in percent inhibition of CXCL1-induced CD11b expression on peripheral blood neutrophils in RSV-infected children <2 years and healthy adults after in vitro incubation with escalating concentrations of danirixin
Inhibition of CD11b upregulation will be evaluated to determine if there is a similar concentration-response relationship between healthy adults and RSV-infected children
Time frame: Day 1
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