Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 | Experimental | Blood sample will be collected from the RSV-infected children <2 years and healthy adults participants. Escalating concentrations of CXCL1 will be added to whole blood in vitro and CD11b up regulation on peripheral blood neutrophils will be analyzed |
|
| Part 2 | Experimental | Blood sample will be collected from the RSV-infected children <2 years and healthy adults participants. Escalating concentrations of danirixin will be added to whole blood in vitro with a fixed concentration of CXCL1 to determine inhibition of CD11b expression on peripheral blood neutrophils |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danirixin | Drug | Powdered form for in-vitro administration to blood sample |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion Criteria:
Healthy Adults
RSV Infected Children
Exclusion Criteria:
Healthy Adults
RSV Infected Children
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Syracuse | New York | 13210 | United States |
Not provided
| Label | URL |
|---|---|
| Results for study 200591 can be found on the GSK Clinical Study Register. | View source |
Not provided
Not provided
| ID | Term |
|---|---|
| D018357 | Respiratory Syncytial Virus Infections |
| ID | Term |
|---|---|
| D018186 | Pneumovirus Infections |
| D018184 | Paramyxoviridae Infections |
| D018701 | Mononegavirales Infections |
| D012327 | RNA Virus Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C581951 | danirixin |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| CXCL1 |
| Other |
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. |
|
| 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 | Day 1 |
| D014777 | Virus Diseases |
| D007239 | Infections |