Infections, Respiratory Syncytial Virus
Conditions
Keywords
CD11b, Neutrophils, CXCL1, Danirixin, Respiratory Syncytial Virus, Children, CXCR2
Brief summary
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.
Interventions
DRUGDanirixin
Powdered form for in-vitro administration to blood sample
OTHERCXCL1
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy Adults * Male/females aged between 18 and 64 years of age inclusive, at the time of signing the informed consent * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history and physical examination. A subject with a clinical abnormality parameter(s) which is not specifically listed in the inclusion or
Exclusion criteria
, may be included only if the Investigator in consultation with the GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>= 45 kilograms (kg) and body mass index (BMI) within the range 18.5-32 kg/meter\^2 (inclusive). * A female subject is eligible to participate if she is not known to be pregnant by history or delivered within the past 3 months. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. RSV Infected Children * Male/females aged \<2 years, at the time of parent(s)/legal guardian(s) signing the informed consent. * Healthy, except for current RSV-infection, as determined by a responsible and experienced physician, based on a medical evaluation including medical history and physical examination. A subject with a clinical abnormality parameter(s) which is not specifically listed in the inclusion or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 1 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD11b upregulation on peripheral blood neutrophils in RSV-infected children <2 years and healthy adults after in vitro incubation with escalating concentrations of CXCL1 | Day 1 | 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 |
| 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 | Day 1 | Inhibition of CD11b upregulation will be evaluated to determine if there is a similar concentration-response relationship between healthy adults and RSV-infected children |
Countries
United States
Outcome results
None listed