Evaluation of Danirixin (GSK1325756) Inhibition of CD11b Cell Surface Expression
A Single-Center In Vitro Study to Evaluate GSK1325756 Inhibition of CD11b Cell Surface Expression in Healthy Adults and Respiratory Syncytial Virus-Infected Children <2 Years (200591)
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
New York
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Syracuse, New York, United States, 13210
- GSK Investigational Site
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 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 >= 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.
Exclusion Criteria:
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.
- Strenuous exercise within 48 hours prior to the blood collection.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to signing the informed consent in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
RSV Infected Children
- A Child in Care: A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. A child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. A child in care does not include a child who is adopted or has an appointed legal guardian.
- Any clinical infection, besides current RSV 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, HIV, liver / biliary disease, pancreatitis
- Receiving systemic anti-inflammatory or immune modulating medications, including but not limited to, NSAIDS and glucocorticoids, within the past 14 days. All other medications are permitted.
- Past medical history including prematurity <37 weeks, congenital heart disease, chronic lung disease, or immunodeficiency.
- Where participation in the study would result in withdrawal of blood or blood products in excess of 2 mL/kg for 24 hours before or after the study period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to parent(s)/guardian(s) signing the informed consent in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Part 1
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
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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.
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|
Experimental: Part 2
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
|
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.
Powdered form for in-vitro administration to blood sample
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
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
Time Frame: 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).
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Day 1
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
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
Time Frame: 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
|
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
Time Frame: 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
|
Day 1
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- 200591
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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