Trial Outcomes & Findings for A Study to Assess Immunity to Specific Microbial Antigens in Healthy Smokers and Non-smokers and in Subjects With Stable COPD (NCT NCT01516437)

NCT ID: NCT01516437

Last Updated: 2017-05-17

Results Overview

Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per millilitre (EU/mL)

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 73 participants
• Primary outcome timeframe: At Day 0
• Results posted on: 2017-05-17

Participant Flow

During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. 3 enrolled subjects did not receive subject allocations, and were excluded from the study prior to start.

Participant milestones

Measure	HNS Group Healthy non-smokers aged between 45-75 years	HS Group Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Overall Study STARTED	24	24	15	7
Overall Study COMPLETED	24	24	14	6
Overall Study NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Measure	HNS Group Healthy non-smokers aged between 45-75 years	HS Group Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Overall Study Reason not specified	0	0	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years	Total n=70 Participants Total of all reporting groups
Age, Continuous	60 Years STANDARD_DEVIATION 10.10 • n=5 Participants	57.8 Years STANDARD_DEVIATION 8.45 • n=7 Participants	64.1 Years STANDARD_DEVIATION 7.39 • n=5 Participants	61.4 Years STANDARD_DEVIATION 6.75 • n=4 Participants	60.26 Years STANDARD_DEVIATION 8.85 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	33 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	15 Participants n=7 Participants	9 Participants n=5 Participants	5 Participants n=4 Participants	37 Participants n=21 Participants

PRIMARY outcome

Timeframe: At Day 0

Population: 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.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per millilitre (EU/mL)

Outcome measures

Measure	HNS Group n=23 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-protein D Antibody Concentrations	79.5 EU/mL Interval 50.2 to 126.0	66.9 EU/mL Interval 53.1 to 84.3	61.7 EU/mL Interval 48.3 to 78.7	72.8 EU/mL Interval 40.1 to 132.0

PRIMARY outcome

Timeframe: At Month 6

Population: The analysis was performed on the According-to-Protocol cohort at Month 6, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Month 6.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)

Outcome measures

Measure	HNS Group n=13 Participants Healthy non-smokers aged between 45-75 years	HS Group n=6 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-protein D Antibody Concentrations	68.6 EU/mL Interval 50.2 to 93.9	61.0 EU/mL Interval 36.6 to 101.8	—	—

PRIMARY outcome

Timeframe: At Day 0

Population: 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.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-Pneumococcal Histidine Triad D Antibody Concentrations	3786.7 EU/mL Interval 2748.3 to 5217.5	3400.7 EU/mL Interval 2445.3 to 4729.4	3323.9 EU/mL Interval 2128.8 to 5190.1	2563.9 EU/mL Interval 840.5 to 7821.6

PRIMARY outcome

Timeframe: At Month 6

Population: The analysis was performed on the According-to-Protocol cohort at Month 6, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Month 6.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)

Outcome measures

Measure	HNS Group n=14 Participants Healthy non-smokers aged between 45-75 years	HS Group n=6 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-Pneumococcal Histidine Triad D Antibody Concentrations	2521.5 EU/mL Interval 1598.6 to 3977.4	2160.1 EU/mL Interval 863.2 to 5405.5	—	—

PRIMARY outcome

Timeframe: At Day 0

Population: 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.

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.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-pneumolysin Antibody Concentrations	3870.5 EU/mL Interval 2607.0 to 5746.3	3116.7 EU/mL Interval 2097.3 to 4631.8	2804.5 EU/mL Interval 1831.8 to 4293.7	3898.7 EU/mL Interval 1437.4 to 10574.5

PRIMARY outcome

Timeframe: At Month 6

Population: The analysis was performed on the According-to-Protocol cohort at Month 6, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Month 6.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)

Outcome measures

Measure	HNS Group n=14 Participants Healthy non-smokers aged between 45-75 years	HS Group n=6 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Anti-pneumolysin Antibody Concentrations	2275.6 EU/mL Interval 1344.0 to 3853.0	3222.3 EU/mL Interval 1416.5 to 7330.4	—	—

PRIMARY outcome

Timeframe: At Day 0

Population: 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.

Concentrations are presented as geometric mean concentrations (GMCs). The reference seropositivity cut-off value was ≥ 17.8%.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Concentrations for Serum Protein-D Enzymatic Inhibition	10.4 EU/mL Interval 8.9 to 12.1	9.3 EU/mL Interval 8.5 to 10.0	9.9 EU/mL Interval 8.4 to 11.7	8.9 EU/mL Interval 8.9 to 8.9

PRIMARY outcome

Timeframe: At Month 6

Population: The analysis was performed on the According-to-Protocol cohort at Month 6, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Month 6.

Concentrations are presented as geometric mean concentrations (GMCs). The reference seropositivity cut-off value was ≥ 17.8%.

Outcome measures

Measure	HNS Group n=14 Participants Healthy non-smokers aged between 45-75 years	HS Group n=6 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Concentrations for Serum Protein-D Enzymatic Inhibition	9.4 EU/mL Interval 8.4 to 10.4	8.9 EU/mL Interval 8.9 to 8.9	—	—

PRIMARY outcome

Timeframe: At Day 0

Population: 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.

Concentrations were expressed as geometric mean concentrations (GMCs)

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Number of Subjects With PD Enzymatic Inhibition Concentration Greater Than or Equal to (≥) 17.8%	4 Subjects	1 Subjects	2 Subjects	0 Subjects

PRIMARY outcome

Timeframe: At Month 6

Population: The analysis was performed on the According-to-Protocol cohort at Month 6, which included all evaluable subjects for whom at least one assay results was available for the blood samples collected at Month 6.

Concentrations were expressed as geometric mean concentrations (GMCs)

Outcome measures

Measure	HNS Group n=14 Participants Healthy non-smokers aged between 45-75 years	HS Group n=6 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Number of Subjects With PD Enzymatic Inhibition Concentration Greater Than or Equal to (≥) 17.8%	1 Subjects	0 Subjects	—	—

SECONDARY outcome

Timeframe: At Day 0

Population: 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.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
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	159.6 T cells/million cells Standard Deviation 67.29	163.5 T cells/million cells Standard Deviation 87.11	173.9 T cells/million cells Standard Deviation 89.69	170.1 T cells/million cells Standard Deviation 88.96

SECONDARY outcome

Timeframe: At Day 0

Population: 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.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
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	97.9 T cells/million cells Standard Deviation 56.74	125.2 T cells/million cells Standard Deviation 73.93	125.2 T cells/million cells Standard Deviation 44.12	161.3 T cells/million cells Standard Deviation 43.72

SECONDARY outcome

Timeframe: At Day 0

Population: 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.

Outcome measures

Measure	HNS Group n=15 Participants Healthy non-smokers aged between 45-75 years	HS Group n=7 Participants Healthy smokers aged between 45-75 years	FeCOPD Group COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Number of Subjects With Positive Sputum - Culture Testing Results Any bacteria	9 Subjects	1 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Streptococcus pneumoniae	0 Subjects	0 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Haemophilus influenzae	2 Subjects	1 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Moraxella catarrhalis	2 Subjects	0 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Staphylococcus aureus	1 Subjects	0 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Pseudomonas aeruginosa	0 Subjects	0 Subjects	—	—
Number of Subjects With Positive Sputum - Culture Testing Results Other bacteria	6 Subjects	0 Subjects	—	—

SECONDARY outcome

Timeframe: At Day 0

Population: 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.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Any bacteria	4 Subjects	1 Subjects	4 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Streptococcus pneumoniae	0 Subjects	1 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Haemophilus influenzae	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Moxarella catarrhalis	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Staphylococcus aureus	4 Subjects	0 Subjects	3 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Pseudomonas aeruginosa	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Nasopharyngeal Swab - Culture Testing Results Other bacteria	0 Subjects	0 Subjects	1 Subjects	0 Subjects

SECONDARY outcome

Timeframe: At Day 0

Population: 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.

Outcome measures

Measure	HNS Group n=24 Participants Healthy non-smokers aged between 45-75 years	HS Group n=24 Participants Healthy smokers aged between 45-75 years	FeCOPD Group n=15 Participants COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 Participants COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Any bacteria	5 Subjects	3 Subjects	5 Subjects	1 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Streptococcus pneumoniae	0 Subjects	1 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Haemophilus influenzae	2 Subjects	1 Subjects	2 Subjects	0 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Moxarella catarrhalis	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Staphylococcus aureus	1 Subjects	1 Subjects	1 Subjects	0 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Pseudomonas aeruginosa	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Oropharyngeal Swab - Culture Testing Results Other bacteria	2 Subjects	0 Subjects	4 Subjects	1 Subjects

Adverse Events

HNS Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

HS Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

FeCOPD Group

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

NFeCOPD Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	HNS Group n=24 participants at risk Healthy non-smokers aged between 45-75 years	HS Group n=24 participants at risk Healthy smokers aged between 45-75 years	FeCOPD Group n=15 participants at risk COPD subjects with ≥ two exacerbations within 365 days prior to the screening visit (frequent exacerbators), aged between 45-75 years	NFeCOPD Group n=7 participants at risk COPD patients with one exacerbation within 365 days prior to the screening visit (non-frequent exacerbators), aged between 45-75 years
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/24 • Serious Adverse Events (SAEs) up to Month 6. Non-serious/frequent adverse events were not collected in this study.	0.00% 0/24 • Serious Adverse Events (SAEs) up to Month 6. Non-serious/frequent adverse events were not collected in this study.	6.7% 1/15 • Serious Adverse Events (SAEs) up to Month 6. Non-serious/frequent adverse events were not collected in this study.	0.00% 0/7 • Serious Adverse Events (SAEs) up to Month 6. Non-serious/frequent adverse events were not collected in this study.

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER