Evaluation of Danirixin (GSK1325756) Inhibition of CD11b Cell Surface Expression

NCT02201303 | Completed Phase 1

• 1 other identifier: 200591
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Infections, Respiratory Syncytial Virus

Keywords

CD11b; Neutrophils; CXCL1; Danirixin; Respiratory Syncytial Virus; Children; CXCR2

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

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

Other: CXCL1

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

Drug: Danirixin; Other: CXCL1

Interventions

Danirixin DRUG

Powdered form for in-vitro administration to blood sample

Part 2

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.

Part 1; Part 2

Eligibility Criteria

• Age: Up to 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy Adults
• Male/females aged between 18 and 64 years of age inclusive, at the time of signing the informed consent

You may not qualify if:

• 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.
• Body weight \>= 3.5 kg
• Documented RSV-infection, either by RSV-antigen or RSV-PCR
• RSV-infection clinical symptom onset within 5 days of blood draw based on parent(s)/guardian(s) history.
• Parent(s)/legal guardian(s) of child capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Healthy Adults
• Any clinical infection within the past 14 days per subject's history.
• Acute or chronic infectious/inflammatory diseases by history, including but not limited to, hepatitis B, hepatitis C, human immuno virus (HIV), inflammatory bowel disease, liver / biliary disease, pancreatitis, arthritis.
• Receiving systemic anti-inflammatory or immune modulating medications, including but not limited to, non-steroidal anti-inflammatory (NSAIDS) and glucocorticoids, within the past 14 days. All other medications are permitted.
• Any alcoholic beverage within 24 hours of blood collection and history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

Related Links

• Results for study 200591 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

danirixin

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: July 28, 2014
• Study Start: January 13, 2014
• Primary Completion: July 2, 2015
• Study Completion: July 2, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)