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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Respiratory Disorders

Intervention / Treatment
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* Procedure: Blood collection
* Procedure: Swab collection
* Procedure: Sputum collection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary disease (COPD)