A Study to Assess Immunity to Specific Microbial Antigens in Healthy Smokers and Non-smokers and in Subjects With Stable COPD

A Study to Assess Immunity to Specific Microbial Antigens in Healthy Smokers and Non-smokers and in Subjects With Stable Chronic Obstructive Pulmonary Disease (COPD) Aged Between 45-75 Years

The present study aims to assess the natural immunity to specific microbial antigens in healthy subjects and in subjects with stable COPD aged between 45-75 years.

Study Overview

• Status: Completed
• Conditions: Respiratory Disorders
• Intervention / Treatment: Procedure: Blood collection; Procedure: Swab collection; Procedure: Sputum collection

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy subjects (smokers and non-smokers)

• Subjects who the investigator believes can and will comply with the requirements of the protocol.
• A male or female between, and including 45 and 75 years of age at the time of consent.
• Written informed consent obtained from the subject.
• Baseline post-bronchodilator Forced Expiratory Volume of air in one second (FEV1) > 85% of predicted normal values and baseline post-bronchodilator FEV1/Forced expiratory Vital Capacity (FVC) > 70% of predicted normal values.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.
• Non-smokers: subjects who never smoked OR
• Smokers: current smoker having a smoking history ≥ 10 pack-years.

COPD subjects (frequent and non-frequent exacerbators)

• Subjects who the investigator believes can and will comply with the requirements of the protocol.
• A male or female between, and including 45 and 75 years of age at the time of consent.
• Written informed consent obtained from the subject.
• Baseline post-bronchodilator FEV1 < 80% and >30% of predicted normal values and baseline post-bronchodilator FEV1/FVC < 70% of predicted normal values.
• Current or former smoker having a smoking history of ≥ 10 pack-years.
• Documented history of ≥ one exacerbation within 365 days prior to the screening visit that required treatment with systemic corticosteroids or resulted in hospitalization.

Exclusion Criteria:

Healthy subjects (smokers and non-smokers)

• Use of any investigational or non-registered product within 30 days prior to Screening Visit or planned use during the study.
• Concurrently participating in another clinical study in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Any known clinically significant anaemia or any other condition as per medical records that would preclude the drawing of blood as described in the protocol.
• Receipt of any vaccine within 30 days preceding blood sampling.
• Previous vaccination with any NTHi vaccine.
• Chronic administration of immunosuppressants or other immune-modifying drugs within 180 days prior to screening visit. Topical steroids are allowed.
• Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
• Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
• Any known respiratory disorders.
• Acute disease and/or fever at the time of the Screening Visit or Visit 1, as applicable
• Receipt of immunoglobulins and/or any blood products within 90 days prior to Screening Visit.
• Receipt of interferon within 90 days prior to Screening Visit.
• History of malignancy.
• Subjects with a history of, or current, alcohol or substance abuse.
• Known history of immune-mediated disorder.
• Recent use of antibiotics or antiviral drug within 30 days prior to Screening Visit.
• Pregnant female.
• Other conditions that the investigator judges may interfere with study findings.

COPD subjects (frequent and non-frequent exacerbators)

• Use of any investigational or non-registered product within 30 days prior to Screening Visit or planned use during the study. Use of investigational inhaled long acting muscarinic antagonists (LAMA), inhaled long acting beta agonists (LABA) or inhaled corticosteroids is allowed.
• Concurrently participating in another clinical study in which the subject has been or will be exposed to an investigational or a non-investigational product. Subjects participating in clinical studies with investigational inhaled LAMA and/or LABA and/or inhaled corticosteroids can be enrolled.
• Any known clinically significant anaemia or any other condition as per medical records that would preclude the drawing of blood as described in the protocol.
• Receipt of any vaccine within 30 days preceding blood sampling.
• Previous vaccination with any NTHi vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
• Serious, uncontrolled disease likely to interfere with the study findings.
• Acute disease and/or fever at the time of the Screening Visit or Visit 1, as applicable
• Receipt of immunoglobulins and/or any blood products within 90 days prior to Screening Visit.
• Receipt of interferon within 90 days prior to Screening Visit.
• History of malignancy.
• Subjects with a history of, or current, alcohol or substance abuse.
• Known history of immune-mediated disease other than COPD.
• Recent use of antibiotics or antiviral drug within 30 days prior to Screening Visit.
• Subject who experienced COPD exacerbation which required antibiotic, systemic corticosteroid or hospitalisation and which did not resolve at least one month prior to Screening Visit and at least 30 days following the last dose of oral corticosteroids.
• Chronic administration of immunosuppressants or other immune-modifying drugs within 180 days preceding screening visit.
• Subjects with very severe COPD, GOLD stage IV.
• Primary diagnosis of asthma.
• Other respiratory disorders such as sarcoidosis, tuberculosis, lung cancer, lung fibrosis, cystic fibrosis.
• A known diagnosis of α-1 antitrypsin deficiency as underlying cause of COPD.
• History of lung surgery.
• Pregnant female.
• Other conditions that the investigator judges may interfere with study findings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HNS Group; Healthy non-smokers aged between 45-75 years	Procedure: Blood collection; Blood collection at Day 0 (all subjects) and at Month 6 (COPD subjects) for the analysis of serology, cell-mediated immune response.; Procedure: Swab collection; Nasopharyngeal and oropharyngeal swabs collection at Day 0 (All subjects) and at exacerbation visits (COPD subjects).
Experimental: HS Group; Healthy smokers aged between 45-75 years	Procedure: Blood collection; Blood collection at Day 0 (all subjects) and at Month 6 (COPD subjects) for the analysis of serology, cell-mediated immune response.; Procedure: Swab collection; Nasopharyngeal and oropharyngeal swabs collection at Day 0 (All subjects) and at exacerbation visits (COPD subjects).
Experimental: FeCOPD Group; COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	Procedure: Blood collection; Blood collection at Day 0 (all subjects) and at Month 6 (COPD subjects) for the analysis of serology, cell-mediated immune response.; Procedure: Swab collection; Nasopharyngeal and oropharyngeal swabs collection at Day 0 (All subjects) and at exacerbation visits (COPD subjects).; Procedure: Sputum collection; Sputum collection at Day 0 and at exacerbation visits (COPD subjects)
Experimental: NFeCOPD Group; COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years	Procedure: Blood collection; Blood collection at Day 0 (all subjects) and at Month 6 (COPD subjects) for the analysis of serology, cell-mediated immune response.; Procedure: Swab collection; Nasopharyngeal and oropharyngeal swabs collection at Day 0 (All subjects) and at exacerbation visits (COPD subjects).; Procedure: Sputum collection; Sputum collection at Day 0 and at exacerbation visits (COPD subjects)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-protein D Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per millilitre (EU/mL)	At Day 0
Anti-protein D Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)	At Month 6
Anti-Pneumococcal Histidine Triad D Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)	At Day 0
Anti-Pneumococcal Histidine Triad D Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)	At Month 6
Anti-pneumolysin Antibody Concentrations	The analysis was performed on the According-to-Protocol cohort at Day 0, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Day 0.	At Day 0
Anti-pneumolysin Antibody Concentrations	Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)	At Month 6
Concentrations for Serum Protein-D Enzymatic Inhibition	Concentrations are presented as geometric mean concentrations (GMCs). The reference seropositivity cut-off value was ≥ 17.8%.	At Day 0
Concentrations for Serum Protein-D Enzymatic Inhibition	Concentrations are presented as geometric mean concentrations (GMCs). The reference seropositivity cut-off value was ≥ 17.8%.	At Month 6
Number of Subjects With PD Enzymatic Inhibition Concentration Greater Than or Equal to (≥) 17.8%	Concentrations were expressed as geometric mean concentrations (GMCs)	At Day 0
Number of Subjects With PD Enzymatic Inhibition Concentration Greater Than or Equal to (≥) 17.8%	Concentrations were expressed as geometric mean concentrations (GMCs)	At Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of Specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among CD 40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α), Interferon-γ (IFN-γ), IL-13 and IL-17 Upon in Vitro Stimulation	At Day 0
Frequency of Specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among CD 40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α), Interferon-γ (IFN-γ), IL-13 and IL-17 Upon in Vitro Stimulation	At Day 0
Number of Subjects With Positive Sputum - Culture Testing Results	At Day 0
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results	At Day 0
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results	At Day 0

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): June 28, 2012
• Study Completion (Actual): December 20, 2012

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary disease (COPD)
• Additional Relevant MeSH Terms: Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: 116021