Respiratory Disorders
Conditions
Keywords
Immunogenicity, Vaccination, Chronic Obstructive Pulmonary Disease, Non-typeable Haemophilus influenzae, Acute exacerbation of COPD, Moraxella catarrhalis, Efficacy, Safety
Brief summary
The purpose of this study is to test if the vaccine is working well in COPD patients aged 40 to 80 years old to reduce episodes of worsening symptoms (exacerbations) and to gather further information on safety and immune response. In the current study, COPD patients with a history of acute exacerbations will receive 2 doses of the investigational vaccine or placebo intramuscularly according to a 0, 2 month vaccination schedule, in addition to standard care. The effect of vaccination against two pathogens known to cause exacerbations (Non-typeable Haemophilus influenza \[NTHi\] and Moraxella catarrhalis \[Mcat\]) will be evaluated at pre-defined timepoints (scheduled study visits). In addition to the scheduled study visits, additional study visit(s) and/ or phone contact(s) will take place for each acute exacerbation of COPD occurring from first vaccination up to study conclusion.
Detailed description
The purpose of this Phase IIB proof-of-concept (POC) study in moderate to very severe COPD patients (i.e. GOLD grade 2, 3 and 4) aged 40 to 80 years with a history of moderate or severe acute exacerbations of COPD (AECOPD) in the previous 12 months is to evaluate whether the NTHi-Mcat vaccine can reduce the frequency of AECOPD in this population and to assess the vaccine's safety, reactogenicity and immunogenicity. Several formulations of a vaccine containing the NTHi antigens (low or high formulation) either non-adjuvanted or combined with different adjuvants (aluminium \[Al\], adjuvant system) were already evaluated in two previous Phase I clinical trials (NTHI-002 in healthy adults aged 18 - 40 years and NTHI-003 in current and former healthy smokers of 50-70 years old). The investigational vaccines were well-tolerated, with an acceptable safety and reactogenicity profile. These studies allowed the dose selection of the NTHi antigens (low formulation) and the adjuvant system currently evaluated for the first time in moderate and severe COPD patients aged 45 - 81 years in the Phase II study NTHI-004. The safety, reactogenicity and immunogenicity of different formulations of the NTHi-Mcat investigational vaccine have been evaluated in the Phase I study in healthy adults aged 19 - 40 years and in current and former smokers aged 50 - 70 years (study NTHI MCAT-001). Based on results obtained up to 30 days post-Dose 2 from this study, the adjuvanted formulation containing NTHi proteins PD and PE-PilA and of UspA2 has been selected for evaluation in the current NTHI MCAT-002 study. Placebo will be used as a control. The NTHi-Mcat investigational vaccine and placebo will be given on top of standard of care to subjects in the respective study groups. In the current study, moderate, severe and very severe COPD patients (i.e. GOLD grade 2, 3 and 4) with a history of AECOPD will receive 2 doses of the NTHi-Mcat investigational vaccine or placebo intramuscularly (IM) according to a 0, 2 month vaccination schedule, in addition to standard care. Scheduled study visits, during which the effect of immunisation against NTHi and Mcat will be evaluated, will take place at pre-defined timepoints. In addition to the scheduled study visits, ad hoc AECOPD-driven study visit(s) and/ or phone contact(s) will take place for each AECOPD occurring from first vaccination up to study conclusion: * An AECOPD visit will be scheduled as soon as possible after the onset of the AECOPD symptoms (maximum 96 hours after the onset of the symptoms). * Follow-up visit(s) and/or phone call(s) will take place to determine the end of the AECOPD. Rationale for the protocol amendment: * CD8+ T cell component was removed from the secondary endpoint, but kept in the exploratory/tertiary endpoint. Previous clinical studies have shown that the investigational NTHi and NTHi-Mcat vaccines do not induce CD8+ T cell responses. This was observed in all studies performed with the NTHi vaccine and seen in the interim analysis of NTHi Mcat-001 study. * An exclusion criterion was updated to clarify that only subjects with clinically significant respiratory diseases other than COPD (e.g. clinically significant lung fibrosis, clinically significant pulmonary embolism) need to be excluded from study participation. * The polymerase chain reaction (PCR) assay for sputum samples was not designed to discriminate amongst Haemophilus influenzae (Hi) serotypes. Results from AERIS epidemiological study \[Wilkinson, 2017\] showed that more than 99% of these bacteria would be Non-Typeable Haemophilus influenzae (NTHi). Therefore, the protocol was updated to clarify that the presence of Hi bacteria in sputum during exacerbation will be used to determine AECOPD associated to NTHi. * The list of potential immune mediated diseases was updated (effective June 30th 2017). * The 87% confidence interval (CI) was removed from all secondary analyses. This confidence interval will only be maintained for the primary analysis because the 95% CIs are underpowered for this study. All other sensitivity analyses on different cohorts will be described using 95% CIs. As the primary objective will have both 87% and 95%, the sensitivity analyses can be interpreted with 95% CIs. * A Full-Analysis Set (FAS) that corresponds to an intent-to-treat analysis was added. The FAS will include all randomized subjects who will receive at least 1 vaccine administration and, as per intention-to-treat principle, a subject in the FAS will be analysed as randomized (i.e. according to the vaccine a subject was planned to receive irrespectively of his/her real exposure). * Cut-off values for anti-PE, anti-PilA and anti-UspA2 antibody ELISAs were updated following the re-set up of the assays. * Additional minor updates were based on the scientific and operational experience gained from current COPD studies.
Interventions
Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.
BIOLOGICALPlacebo
Two doses administered intramuscularly at Day 1 and Day 61 in the deltoid region of the non-dominant arm.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data will be collected in an observer-blind manner. By observer-blind, it is meant that during the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity and efficacy) will all be unaware of whether vaccine or placebo was administered. Each study site is responsible for having a blinding plan. To work in an observer-blind manner, vaccine preparation and administration will be done by authorised medical personnel who will not participate in any of the study clinical evaluation assays. Two teams of study personnel will hence be set up: * A team of unblinded personnel (responsible for the preparation and the administration of the vaccines) * A team of blinded personnel (responsible for the clinical evaluation of the subjects).
Intervention model description
Phase IIB, randomised, observer-blind, placebo-controlled, multi-centric study with two parallel groups.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written informed consent obtained from the subject prior to performing any study specific procedure. * A male or female between, and including, 40 and 80 years of age at the time of the first vaccination. * Confirmed diagnosis of COPD with forced expiratory volume in 1 second (FEV1) over forced vital capacity (FVC) ratio (FEV1/FVC) \< 0.7, AND FEV1 \< 80% predicted (GOLD 2, 3 and 4). * Current or former smoker with a cigarette smoking history of ≥ 10 pack-years. * Stable COPD patient\* with documented history\*\* of at least 1 moderate or severe AECOPD within the 12 months before Screening. * Patient for whom the last episode of AECOPD is resolved for at least 30 days at the time of first vaccination. * A documented history of a COPD exacerbation is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence. Subject verbal reports are not acceptable. * Capable of complying with the daily electronic Diary Card completion throughout the study period, according to investigator's judgement at Visit 1. * Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. * Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
Exclusion criteria
* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine, with the exception of any influenza or pneumococcal vaccine which may be administered ≥15 days preceding or following any study vaccine dose. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product. * Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose (e.g. methotrexate). * Administration of systemic corticosteroids within the 30 days before first vaccination. Subjects who received systemic corticosteroids within this period may be enrolled at a later date if enrolment is still open. Inhaled and topical steroids are allowed. • Administration of systemic antibiotics within the 30 days before first vaccination. Subjects who received systemic antibiotics within this period may be enrolled at a later date if enrolment is still open. * Chronic use of antibiotics for prevention of AECOPD (e.g. azithromycin). * Acute disease and/or fever at the time of first vaccination. Fever is defined as temperature ≥37.5°C. The preferred location for measuring temperature in this study will be the oral cavity or the axilla. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. * Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy \>3L/min (Oxygen use ≤3L/min flow is not exclusionary). * Planned lung transplantation. * Lung resection: Subjects with planned lung volume reduction surgery during the study or within the 12 months prior to first vaccination. * Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD. * Diagnosed with a respiratory disorder other than COPD at time of enrolment (such as sarcoidosis, active tuberculosis, clinically significant bronchiectasis, clinically significant lung fibrosis, clinically significant pulmonary embolism, clinically significant pneumothorax, current diagnosis of asthma in the opinion of the investigator), or chest X-ray/ CT scan revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Subjects with allergic rhinitis do not need to be excluded and may be enrolled at the discretion of the investigator. * History of immune-mediated disease other than COPD. If the subject has any condition on the non-exhaustive list of potential immune-mediated diseases defined in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated. * Previous vaccination with any vaccine containing NTHi and/ or Mcat antigens. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines and/ or the bronchodilator used for spirometry assessment during the study. * Contraindication for spirometry testing. * Unstable or life threatening cardiac disease: subjects with any of the following at Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the last 6 months. Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months NYHA Class IV Heart failure * Malignancies within the previous 5 years or lymphoproliferative disorder. * Any known disease or condition likely to cause death during the study period. * Pregnant or lactating female. * Current alcoholism and/or drug abuse. * Other condition which the investigator judges may put the safety of the subject at risk through study participation or which may interfere with the study findings. * Planned move to a location that will complicate participation in the trial through study end.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement. |
| Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reported With Any Unsolicited Adverse Event (AE) | During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61 | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for any solicited symptoms. |
| Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs) | From first vaccination (Day 1) up to Study end (at Day 451) | pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. |
| Number of Subjects Reported With Any Serious Adverse Event (SAE) | From first vaccination (Day 1) up to Study end (at Day 451) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity |
| Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2) | The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The severity of AECOPD can be graded according to the intensity of medical intervention required. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months. |
| Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months, 0-12 months (observation starting 1 month post-Dose 2) | The rates of any AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The intention of the analysis of the Rate during 3, 6, 9 and 12 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 and 0-12 months. |
| Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2) | The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: It is calculated proportionally to the follow-up time per subject and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for each period considered. The severity of AECOPD can be graded according to the intensity of medical intervention required. Mild = can be controlled with an increase in dosage of regular medications. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months. |
| Number of Subjects With First Moderate or Severe AECOPD | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of moderate or severe episode of AECOPD was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. |
| Number of Subjects With First AECOPD of Any Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of any episode of AECOPD of any severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. |
| Number of Subjects With First AECOPD Classified by Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of any episode of AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. |
| Number of Days With Moderate and Severe AECOPDs | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each AECOPD was tabulated and presented via descriptive statistics (mean, Standard Deviation) and expressed in Days. |
| Number of Days With AECOPDs of Any Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
| Number of Days With AECOPDs Classified by Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each AECOPDs by severity was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
| Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by Polymerase chain reaction (PCR) analysis in sputum samples. |
| Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The rates of AECOPD of any severity were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by polymerase chain reaction (PCR) analysis in sputum samples. |
| Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61 | Assessed solicited local symptoms were pain, redness and swelling |
| Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of moderate or severe NTHI-associated and/or Mcat-associated AECOPD was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples. |
| Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD of any severity was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples. |
| Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples. |
| Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
| Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
| Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
| Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 | Anti-Protein D (PD) antibody concentrations as determined by ELISA, and expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EU/mL). For anti-PD antibodies, the cut-off of the assay is 153 ELISA Units per millilitre (EU/mL.) |
| Anti-PE Antibody Concentrations as Measured by ELISA | At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 | Anti-Protein E (PE) antibody concentrations as determined by ELISA and expressed as GMCs in EU/mL For Anti-PE antibodies, the cut-off of the assay is 16 EU/mL. |
| Anti-PilA Antibody Concentrations as Measured by ELISA | At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 | Anti-Type IV pilus assembly protein (PilA) antibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-PilA antibodies, the cut-off of the assay is 8 EU/mL. |
| Anti-UspA2 Antibody Concentrations as Measured by ELISA | At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 | Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) aantibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-UspA2 antibodies, the cut-off of the assay is 28 EU/mL. |
| Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | At Day 1, Day 91, Day 271 and at Day 451 | The ICS staining assay was used to assess cell-mediated immunogenicity (CMI) responses. After Peripheral blood mononuclear cell (PBMC) stimulation with the relevant antigen, the frequency of PD specific CD4+ T-cells expressing selected combination of cytokines such as interleukine-2, 13, 17 (IL-2, IL-13, IL-17), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation. |
| Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | At Day 1, Day 91, Day 271 and at Day 451 | The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PE specific CD4+ T-cells expressing selected combination of cytokines such as (IL-2, IL-13, IL-17), IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
| Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | At Day 1, Day 91, Day 271 and at Day 451 | The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PilA specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
| Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | At Day 1, Day 91, Day 271 and at Day 451 | The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of UspA2 specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
| Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) | The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: it is calculated proportionally to the follow-up time per subject, and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for the period considered. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples |
| Number of Subjects Reported With Each Solicited General AE | During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61 | Assessed solicited general symptoms were Chills, fatigue, fever \[defined as (oral cavity or axillary) temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache and myalgia. |
Countries
Belgium, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GSK3277511A Group Healthy males and females, 40 to 80 years of age, who received two doses of the adjuvanted GSK3277511A investigational vaccine containing surface protein D (PD), protein E- type IV pilus assembly protein (PE-PilA,) and ubiquitous surface protein A2 (UspA2), administered at Day 1 and Day 61 | 304 |
| Control Group Healthy males and females, 40 to 80 years of age, who received two doses of placebo, administered at Day 1 and Day 61. | 302 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 15 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | MIGRATED / MOVED FROM THE STUDY AREA | 2 | 0 |
| Overall Study | OTHER | 5 | 5 |
| Overall Study | Withdrawal by Subject | 11 | 15 |
Baseline characteristics
| Characteristic | GSK3277511A Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 7.5 | 66.3 Years STANDARD_DEVIATION 7.3 | 66.0 Years STANDARD_DEVIATION 7.4 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Central / South Asian Heritage | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black Or African American | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 294 Participants | 296 Participants | 590 Participants |
| Sex: Female, Male Female | 120 Participants | 125 Participants | 245 Participants |
| Sex: Female, Male Male | 184 Participants | 177 Participants | 361 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 304 | 10 / 302 |
| other Total, other adverse events | 276 / 304 | 247 / 302 |
| serious Total, serious adverse events | 89 / 304 | 99 / 302 |
Outcome results
Primary
Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year
Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3277511A Group | Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year | 1.22 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD (Any Cause)-Analysis (87% Confidence Interval [CI]), Post-dose 2 and Lasting for 1 Year | 1.17 exacerbations per person-year |
Comparison: To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of moderate and severe AECOPDsp-value: 0.815787% CI: [-18.27, 11.58]Negative Binomial regression
Primary
Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year
Efficacy of the investigational vaccine was measured by the rate of moderate and severe AECOPD from 1-month post dose 2 up to study end (i.e. rate expressed per year and calculated as the total number of events over the follow-up exposure time). The CIs of the rate is computed using a model which accounts for repeated events. Anthonisen criteria used to detect potential AECOPD: Worsening of 2 or more of the following major symptoms for at least 2 consecutive days: dyspnoea, sputum volume, sputum purulence, OR Worsening of any major symptom together with any of the following minor symptoms for at least 2 consecutive days: sore throat, cold, fever without other cause, increased cough, increased wheeze. Moderate AECOPD requires treatment with systemic corticosteroids and/ or antibiotics. Severe AECOPD requires hospitalization. Confirmation of any AECOPD was as per investigator's judgement.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3277511A Group | Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year | 1.22 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD (Any Cause) -Analysis (95% CI), Post-dose 2 and Lasting for 1 Year | 1.17 exacerbations per person-year |
Comparison: To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of moderate and severe AECOPDsp-value: 0.815795% CI: [-23.45, 15.29]Negative Binomial regression
Secondary
Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA)
Anti-Protein D (PD) antibody concentrations as determined by ELISA, and expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EU/mL). For anti-PD antibodies, the cut-off of the assay is 153 ELISA Units per millilitre (EU/mL.)
Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol immuno set for analysis of immunogenicity cohort which includes all vaccinated subjects who complied with the vaccination schedule and who have immunogenicity data for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 1 | 103.7 EU/mL. |
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 31 | 1048.1 EU/mL. |
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 271 | 546 EU/mL. |
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 91 | 1521.4 EU/mL. |
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 451 | 444.1 EU/mL. |
| GSK3277511A Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 61 | 654.6 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 451 | 97.9 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 31 | 98.2 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 61 | 95.5 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 91 | 90.3 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 271 | 94.8 EU/mL. |
| Control Group | Anti-PD Antibody Concentrations as Measured by the Enzyme-Linked Immunosorbent Assay (ELISA) | Day 1 | 95.4 EU/mL. |
Secondary
Anti-PE Antibody Concentrations as Measured by ELISA
Anti-Protein E (PE) antibody concentrations as determined by ELISA and expressed as GMCs in EU/mL For Anti-PE antibodies, the cut-off of the assay is 16 EU/mL.
Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol immuno set for analysis of immunogenicity cohort which includes all vaccinated subjects who complied with the vaccination schedule and who have immunogenicity data for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 1 | 20.9 EU/mL. |
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 31 | 1108.1 EU/mL. |
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 61 | 872.8 EU/mL. |
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 91 | 6020 EU/mL. |
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 271 | 1254.9 EU/mL. |
| GSK3277511A Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 451 | 835.2 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 271 | 19.3 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 1 | 21.6 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 91 | 20.1 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 31 | 20.7 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 451 | 19.7 EU/mL. |
| Control Group | Anti-PE Antibody Concentrations as Measured by ELISA | Day 61 | 20.5 EU/mL. |
Secondary
Anti-PilA Antibody Concentrations as Measured by ELISA
Anti-Type IV pilus assembly protein (PilA) antibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-PilA antibodies, the cut-off of the assay is 8 EU/mL.
Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol immuno set for analysis of immunogenicity cohort which includes all vaccinated subjects who complied with the vaccination schedule and who have immunogenicity data for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 1 | 8.3 EU/mL. |
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 31 | 153 EU/mL. |
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 61 | 134.2 EU/mL. |
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 91 | 913.5 EU/mL. |
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 271 | 189.6 EU/mL. |
| GSK3277511A Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 451 | 126.5 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 271 | 8 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 1 | 8.5 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 91 | 8.9 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 31 | 9.2 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 451 | 8.3 EU/mL. |
| Control Group | Anti-PilA Antibody Concentrations as Measured by ELISA | Day 61 | 8.8 EU/mL. |
Secondary
Anti-UspA2 Antibody Concentrations as Measured by ELISA
Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) aantibody concentrations as determined by ELISA, and expressed as GMCs in EU/mL. For Anti-UspA2 antibodies, the cut-off of the assay is 28 EU/mL.
Time frame: At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol immuno set for analysis of immunogenicity cohort which includes all vaccinated subjects who complied with the vaccination schedule and who have immunogenicity data for the specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 61 | 848.7 EU/mL |
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 451 | 575.9 EU/mL |
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 91 | 1223.7 EU/mL |
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 31 | 1092.1 EU/mL |
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 271 | 645.1 EU/mL |
| GSK3277511A Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 1 | 540.3 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 451 | 468.5 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 1 | 604.7 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 31 | 485.2 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 61 | 473.5 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 91 | 446 EU/mL |
| Control Group | Anti-UspA2 Antibody Concentrations as Measured by ELISA | Day 271 | 445.4 EU/mL |
Secondary
Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: It is calculated proportionally to the follow-up time per subject and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for each period considered. The severity of AECOPD can be graded according to the intensity of medical intervention required. Mild = can be controlled with an increase in dosage of regular medications. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.
Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 3 TO 6 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.24 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 9 TO 12 MONTHS | 0.03 exacerbations per person | Standard Deviation 0.17 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 9 TO 12 MONTHS | 0.2 exacerbations per person | Standard Deviation 0.44 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 0 TO 3 MONTHS | 0.02 exacerbations per person | Standard Deviation 0.15 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 0 TO 3 MONTHS | 0.04 exacerbations per person | Standard Deviation 0.24 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 0 TO 3 MONTHS | 0.29 exacerbations per person | Standard Deviation 0.62 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 3 TO 6 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.22 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 6 TO 9 MONTHS | 0.03 exacerbations per person | Standard Deviation 0.19 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 6 TO 9 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.29 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 3 TO 6 MONTHS | 0.27 exacerbations per person | Standard Deviation 0.51 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 9 TO 12 MONTHS | 0.01 exacerbations per person | Standard Deviation 0.11 |
| GSK3277511A Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 6 TO 9 MONTHS | 0.3 exacerbations per person | Standard Deviation 0.56 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 9 TO 12 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.24 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 0 TO 3 MONTHS | 0.03 exacerbations per person | Standard Deviation 0.2 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 3 TO 6 MONTHS | 0.02 exacerbations per person | Standard Deviation 0.14 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 6 TO 9 MONTHS | 0.03 exacerbations per person | Standard Deviation 0.18 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MILD, FROM 9 TO 12 MONTHS | 0.03 exacerbations per person | Standard Deviation 0.16 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 0 TO 3 MONTHS | 0.23 exacerbations per person | Standard Deviation 0.48 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 3 TO 6 MONTHS | 0.3 exacerbations per person | Standard Deviation 0.57 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 6 TO 9 MONTHS | 0.25 exacerbations per person | Standard Deviation 0.51 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | MODERATE, FROM 9 TO 12 MONTHS | 0.17 exacerbations per person | Standard Deviation 0.42 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 0 TO 3 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.23 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 3 TO 6 MONTHS | 0.06 exacerbations per person | Standard Deviation 0.29 |
| Control Group | Exacerbation Rate of Any AECOPD Cases, Classified by Severity, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | SEVERE, FROM 6 TO 9 MONTHS | 0.05 exacerbations per person | Standard Deviation 0.24 |
Secondary
Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity
The exacerbation rate of any AECOPD by severity is the average number of exacerbations for each subject: it is calculated proportionally to the follow-up time per subject, and then scaled to the period considered. Mean and standard deviation of the exacerbation rate are given for the period considered. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | MODERATE, AFTER 1 MONTH POST DOSE 2 | 0.3 exacerbations per person | Standard Deviation 0.67 |
| GSK3277511A Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | MILD, AFTER 1 MONTH POST DOSE 2 | 0.06 exacerbations per person | Standard Deviation 0.28 |
| GSK3277511A Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | SEVERE, AFTER 1 MONTH POST DOSE 2 | 0.02 exacerbations per person | Standard Deviation 0.18 |
| Control Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | MILD, AFTER 1 MONTH POST DOSE 2 | 0.03 exacerbations per person | Standard Deviation 0.21 |
| Control Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | MODERATE, AFTER 1 MONTH POST DOSE 2 | 0.31 exacerbations per person | Standard Deviation 0.74 |
| Control Group | Exacerbation Rate of Any NTHi-associated and/ or Mcat-associated AECOPD Cases, Classified by Severity | SEVERE, AFTER 1 MONTH POST DOSE 2 | 0.01 exacerbations per person | Standard Deviation 0.11 |
Secondary
Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
The ICS staining assay was used to assess cell-mediated immunogenicity (CMI) responses. After Peripheral blood mononuclear cell (PBMC) stimulation with the relevant antigen, the frequency of PD specific CD4+ T-cells expressing selected combination of cytokines such as interleukine-2, 13, 17 (IL-2, IL-13, IL-17), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation.
Time frame: At Day 1, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol CMI set for analysis of immunogenicity cohort which includes all vaccinated subjects who were complied with the vaccination schedule and who have CMI data for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 56.6 T cells/million cells | Standard Deviation 125.7 |
| GSK3277511A Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 890.2 T cells/million cells | Standard Deviation 988.8 |
| GSK3277511A Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 267 T cells/million cells | Standard Deviation 282.6 |
| GSK3277511A Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 364.6 T cells/million cells | Standard Deviation 363.9 |
| Control Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 46.7 T cells/million cells | Standard Deviation 101.1 |
| Control Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 59.7 T cells/million cells | Standard Deviation 118.2 |
| Control Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 55.8 T cells/million cells | Standard Deviation 88.2 |
| Control Group | Frequency of PD Specific Cluster of Differentiation (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 51.8 T cells/million cells | Standard Deviation 90.9 |
Secondary
Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PE specific CD4+ T-cells expressing selected combination of cytokines such as (IL-2, IL-13, IL-17), IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.
Time frame: At Day 1, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol CMI set for analysis of immunogenicity cohort which includes all vaccinated subjects who were complied with the vaccination schedule and who have CMI data for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 63.1 T cells/million cells | Standard Deviation 211.4 |
| GSK3277511A Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 797 T cells/million cells | Standard Deviation 1082.9 |
| GSK3277511A Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 384.8 T cells/million cells | Standard Deviation 539.9 |
| GSK3277511A Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 335.7 T cells/million cells | Standard Deviation 493.7 |
| Control Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 81.2 T cells/million cells | Standard Deviation 258.9 |
| Control Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 92.9 T cells/million cells | Standard Deviation 266 |
| Control Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 61.4 T cells/million cells | Standard Deviation 207.2 |
| Control Group | Frequency of PE Specific (CD)4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 76.2 T cells/million cells | Standard Deviation 195 |
Secondary
Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of PilA specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.
Time frame: At Day 1, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol CMI set for analysis of immunogenicity cohort which includes all vaccinated subjects who were complied with the vaccination schedule and who have CMI data for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 141 T cells/million cells | Standard Deviation 147.1 |
| GSK3277511A Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 137.3 T cells/million cells | Standard Deviation 163.2 |
| GSK3277511A Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 26.2 T cells/million cells | Standard Deviation 45.4 |
| GSK3277511A Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 305.8 T cells/million cells | Standard Deviation 321.7 |
| Control Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 42.4 T cells/million cells | Standard Deviation 95.3 |
| Control Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 44.6 T cells/million cells | Standard Deviation 114.8 |
| Control Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 42.1 T cells/million cells | Standard Deviation 78.2 |
| Control Group | Frequency of PilA Specific CD4+ T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 53.3 T cells/million cells | Standard Deviation 95.9 |
Secondary
Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data
The ICS staining assay was used to assess CMI responses. After PBMC stimulation with the relevant antigen, the frequency of UspA2 specific CD4+ T-cells expressing selected combination of cytokines such as IL-2, IL-13, IL-17, IFN-γ, TNF-α and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation.
Time frame: At Day 1, Day 91, Day 271 and at Day 451
Population: The analysis was performed on the Per-Protocol CMI set for analysis of immunogenicity cohort which includes all vaccinated subjects who were complied with the vaccination schedule and who have CMI data for the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 66.1 T cells/million cells | Standard Deviation 177.1 |
| GSK3277511A Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 646.3 T cells/million cells | Standard Deviation 545.2 |
| GSK3277511A Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 330.5 T cells/million cells | Standard Deviation 278.5 |
| GSK3277511A Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 331.3 T cells/million cells | Standard Deviation 310.4 |
| Control Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 451 | 61.5 T cells/million cells | Standard Deviation 89.2 |
| Control Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 1 | 47.2 T cells/million cells | Standard Deviation 85.8 |
| Control Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 271 | 60.8 T cells/million cells | Standard Deviation 80 |
| Control Group | Frequency of UspA2 Specific CD4 + T-cells Expressing at Least 2 Markers Among CD40L, IL2, TNF-Alpha, IFN-Gamma, IL-13 and IL-17 Using Background Reduced Frequency Data | Day 91 | 70.3 T cells/million cells | Standard Deviation 94.6 |
Secondary
Number of Days With AECOPDs Classified by Severity
The length of each AECOPDs by severity was tabulated and presented via descriptive statistics (mean, Standard Deviation).
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Number of Days With AECOPDs Classified by Severity | MILD, AFTER 1 MONTH POST DOSE 2 | 8.9 Days | Standard Deviation 3.56 |
| GSK3277511A Group | Number of Days With AECOPDs Classified by Severity | MODERATE, AFTER 1 MONTH POST DOSE 2 | 16.1 Days | Standard Deviation 13.9 |
| GSK3277511A Group | Number of Days With AECOPDs Classified by Severity | SEVERE, AFTER 1 MONTH POST DOSE 2 | 20.4 Days | Standard Deviation 16.78 |
| Control Group | Number of Days With AECOPDs Classified by Severity | MILD, AFTER 1 MONTH POST DOSE 2 | 12.3 Days | Standard Deviation 9.11 |
| Control Group | Number of Days With AECOPDs Classified by Severity | MODERATE, AFTER 1 MONTH POST DOSE 2 | 14.5 Days | Standard Deviation 10.5 |
| Control Group | Number of Days With AECOPDs Classified by Severity | SEVERE, AFTER 1 MONTH POST DOSE 2 | 21.2 Days | Standard Deviation 23.85 |
Secondary
Number of Days With AECOPDs of Any Severity
The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3277511A Group | Number of Days With AECOPDs of Any Severity | 15.9 Days | Standard Deviation 13.79 |
| Control Group | Number of Days With AECOPDs of Any Severity | 15.3 Days | Standard Deviation 13.51 |
Secondary
Number of Days With Moderate and Severe AECOPDs
The length of each AECOPD was tabulated and presented via descriptive statistics (mean, Standard Deviation) and expressed in Days.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3277511A Group | Number of Days With Moderate and Severe AECOPDs | 16.6 Days | Standard Deviation 14.29 |
| Control Group | Number of Days With Moderate and Severe AECOPDs | 15.6 Days | Standard Deviation 13.93 |
Secondary
Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD
The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3277511A Group | Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD | 14 Days | Standard Deviation 10.43 |
| Control Group | Number of Days With Moderate and Severe NTHi-associated and Mcat-associated AECOPD | 12.3 Days | Standard Deviation 5.59 |
Secondary
Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity
The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK3277511A Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 9.5 Days | Standard Deviation 3.54 |
| GSK3277511A Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 13.8 Days | Standard Deviation 10.41 |
| GSK3277511A Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 17.3 Days | Standard Deviation 11.02 |
| Control Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 9.9 Days | Standard Deviation 6.83 |
| Control Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 12.5 Days | Standard Deviation 5.62 |
| Control Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 7.5 Days | Standard Deviation 1 |
Secondary
Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity
The length of each NTHi associated and/or Mcat associated AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation).
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK3277511A Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity | 13.3 Days | Standard Deviation 9.76 |
| Control Group | Number of Days With NTHi-associated and/or Mcat-associated AECOPDs of Any Severity | 12.1 Days | Standard Deviation 5.72 |
Secondary
Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs)
pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Time frame: From first vaccination (Day 1) up to Study end (at Day 451)
Population: The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided safety data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs) | 6 Participants |
| Control Group | Number of Subjects Reported With Any Potential Immune-mediated Diseases (pIMDs) | 3 Participants |
Secondary
Number of Subjects Reported With Any Serious Adverse Event (SAE)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity
Time frame: From first vaccination (Day 1) up to Study end (at Day 451)
Population: The analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one documented study vaccine administration and who provided safety data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects Reported With Any Serious Adverse Event (SAE) | 89 Participants |
| Control Group | Number of Subjects Reported With Any Serious Adverse Event (SAE) | 99 Participants |
Secondary
Number of Subjects Reported With Any Unsolicited Adverse Event (AE)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for any solicited symptoms.
Time frame: During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61
Population: The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided unsolicited safety data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects Reported With Any Unsolicited Adverse Event (AE) | 110 Participants |
| Control Group | Number of Subjects Reported With Any Unsolicited Adverse Event (AE) | 103 Participants |
Secondary
Number of Subjects Reported With Each Solicited General AE
Assessed solicited general symptoms were Chills, fatigue, fever \[defined as (oral cavity or axillary) temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache and myalgia.
Time frame: During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61
Population: The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided solicited safey data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Chills, Dose 1 | 29 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Fever, Dose 2 | 18 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Fatigue, Dose 1 | 157 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Gastrointestinal symptoms, Dose 1 | 47 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Headache, Dose 2 | 75 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Gastrointestinal symptoms, Dose 2 | 39 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Fatigue, Dose 2 | 136 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Headache, Dose 1 | 98 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Chills, Dose 2 | 35 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Fever, Dose 1 | 24 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Myalgia, Dose 1 | 78 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited General AE | Myalgia, Dose 2 | 74 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Myalgia, Dose 1 | 72 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Myalgia, Dose 2 | 43 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Chills, Dose 1 | 35 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Chills, Dose 2 | 28 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Fatigue, Dose 1 | 167 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Fatigue, Dose 2 | 130 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Fever, Dose 1 | 25 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Fever, Dose 2 | 11 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Gastrointestinal symptoms, Dose 1 | 54 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Gastrointestinal symptoms, Dose 2 | 35 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Headache, Dose 1 | 76 Participants |
| Control Group | Number of Subjects Reported With Each Solicited General AE | Headache, Dose 2 | 64 Participants |
Secondary
Number of Subjects Reported With Each Solicited Local Adverse Event (AE)
Assessed solicited local symptoms were pain, redness and swelling
Time frame: During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61
Population: The analysis was performed on the Total Vaccinated cohort which includes all vaccinated subjects with at least one documented study vaccine administration and who provided solicited safey data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Pain, Dose 1 | 153 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Pain, Dose 2 | 163 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Redness (mm), Dose 1 | 18 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Redness (mm), Dose 2 | 37 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Swelling (mm), Dose 1 | 13 Participants |
| GSK3277511A Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Swelling (mm), Dose 2 | 31 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Swelling (mm), Dose 1 | 2 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Pain, Dose 1 | 16 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Redness (mm), Dose 2 | 0 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Pain, Dose 2 | 13 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Swelling (mm), Dose 2 | 0 Participants |
| Control Group | Number of Subjects Reported With Each Solicited Local Adverse Event (AE) | Redness (mm), Dose 1 | 1 Participants |
Secondary
Number of Subjects With First AECOPD Classified by Severity
Number of subjects with first occurrence of any episode of AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3277511A Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 144 Participants |
| GSK3277511A Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 27 Participants |
| GSK3277511A Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 30 Participants |
| Control Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 27 Participants |
| Control Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 154 Participants |
| Control Group | Number of Subjects With First AECOPD Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 41 Participants |
Comparison: Hazard rate for mild AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.858195% CI: [0.616, 1.791]Regression, Cox
Comparison: Hazard rate for moderate AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.963495% CI: [0.792, 1.249]Regression, Cox
Comparison: Hazard rate for severe AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.175595% CI: [0.45, 1.157]Regression, Cox
Secondary
Number of Subjects With First AECOPD of Any Severity
Number of subjects with first occurrence of any episode of AECOPD of any severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects With First AECOPD of Any Severity | 168 Participants |
| Control Group | Number of Subjects With First AECOPD of Any Severity | 188 Participants |
Comparison: Hazard rate for any AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.519495% CI: [0.758, 1.15]Regression, Cox
Secondary
Number of Subjects With First Moderate or Severe AECOPD
Number of subjects with first occurrence of moderate or severe episode of AECOPD was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects With First Moderate or Severe AECOPD | 158 Participants |
| Control Group | Number of Subjects With First Moderate or Severe AECOPD | 176 Participants |
Comparison: Hazard rate for moderate or severe AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.575195% CI: [0.758, 1.166]Regression, Cox
Secondary
Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD
Number of subjects with first occurrence of moderate or severe NTHI-associated and/or Mcat-associated AECOPD was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD | 62 Participants |
| Control Group | Number of Subjects With First Moderate or Severe NTHi-associated and/or Mcat-associated AECOPD | 62 Participants |
Comparison: Hazard rate for moderate or severe NTHi-associated and/or Mcat-associated AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.946395% CI: [0.73, 1.477]Regression, Cox
Secondary
Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity
Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD classified by severity was reported, in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3277511A Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 15 Participants |
| GSK3277511A Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 58 Participants |
| GSK3277511A Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 4 Participants |
| Control Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, SEVERE | 4 Participants |
| Control Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MILD | 7 Participants |
| Control Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD, Classified by Severity | AFTER 1 MONTH POST DOSE 2, MODERATE | 59 Participants |
Comparison: Hazard rate for mild NTHi-associated and/or Mcat-associated AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.077795% CI: [0.914, 5.504]Regression, Cox
Comparison: Hazard rate for moderate NTHi-associated and/or Mcat-associated AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.912195% CI: [0.71, 1.467]Regression, Cox
Comparison: Hazard rate for severe NTHi-associated and/or Mcat-associated AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.873795% CI: [0.278, 4.502]Regression, Cox
Secondary
Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity
Number of subjects with first occurrence of NTHI-associated and/or Mcat-associated AECOPD of any severity was reported,in order to compute time to first occurrence and derive the hazard rate using Cox's proportional hazard regression model. Respiratory pathogens NTHi and Mcat was determined PCR analysis in sputum samples.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3277511A Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity | 70 Participants |
| Control Group | Number of Subjects With First NTHi-associated and/or Mcat-associated AECOPD of Any Severity | 67 Participants |
Comparison: Hazard rate for any NTHi-associated and/or Mcat-associated AECOPDs, one year follow-up starting 1 month post dose 2p-value: 0.604295% CI: [0.782, 1.528]Regression, Cox
Secondary
Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
The rates of any AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The intention of the analysis of the Rate during 3, 6, 9 and 12 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 and 0-12 months.
Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months, 0-12 months (observation starting 1 month post-Dose 2)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3277511A Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 6 TO 9 MONTHS | 1.49 exacerbations per person-year |
| GSK3277511A Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 3 TO 6 MONTHS | 1.56 exacerbations per person-year |
| GSK3277511A Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 9 TO 12 MONTHS | 0.98 exacerbations per person-year |
| GSK3277511A Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | From 0 TO 12 MONTHS | 1.36 exacerbations per person-year |
| GSK3277511A Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 0 TO 3 MONTHS | 1.47 exacerbations per person-year |
| Control Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | From 0 TO 12 MONTHS | 1.31 exacerbations per person-year |
| Control Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 0 TO 3 MONTHS | 1.33 exacerbations per person-year |
| Control Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 3 TO 6 MONTHS | 1.56 exacerbations per person-year |
| Control Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 6 TO 9 MONTHS | 1.29 exacerbations per person-year |
| Control Group | Rate of Any AECOPD Case in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 9 TO 12 MONTHS | 1.04 exacerbations per person-year |
Comparison: To assess efficacy of the investigational vaccine as compared to the placebo control with respect to the rate of AECOPDs of any severity- upto 12 months follow up periodp-value: 0.7795% CI: [-22.95, 14.19]Negative Binomial regression
Secondary
Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period
The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. The severity of AECOPD can be graded according to the intensity of medical intervention required. Moderate AECOPD= requires treatment with systemic corticosteroids and/or antibiotics. Severe AECOPD= requires hospitalization. The intention of the analysis of the Rate during 3, 6 and 9 months observation starting 1 month post-Dose 2 was to report the rate by 3 months period, so for the periods: 0-3, 3-6, 6-9, 9-12 months.
Time frame: During following periods: from 0 to 3 months, from 3 to 6 months, from 6 to 9 months, from 9 to 12 months (observation starting 1 month post-Dose 2)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GSK3277511A Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 0 TO 3 MONTHS | 1.35 exacerbations per person-year |
| GSK3277511A Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 3 TO 6 MONTHS | 1.33 exacerbations per person-year |
| GSK3277511A Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 6 TO 9 MONTHS | 1.36 exacerbations per person-year |
| GSK3277511A Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 9 TO 12 MONTHS | 0.87 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 9 TO 12 MONTHS | 0.9 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 0 TO 3 MONTHS | 1.15 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 6 TO 9 MONTHS | 1.19 exacerbations per person-year |
| Control Group | Rate of Moderate and Severe AECOPD in Vaccinated and Control Subjects, One Year Follow up Starting 1 Month Post Dose 2, by 3 Months Period | FROM 3 TO 6 MONTHS | 1.44 exacerbations per person-year |
Secondary
Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD
The rates of AECOPD were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by Polymerase chain reaction (PCR) analysis in sputum samples.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3277511A Group | Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD | 0.32 exacerbations per person-year |
| Control Group | Rate of Non-Typeable Haemophilus Influenzae (NTHi)-Associated and/ or Moraxella Catarrhalis (Mcat)-Associated Moderate and Severe AECOPD | 0.32 exacerbations per person-year |
Secondary
Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity
The rates of AECOPD of any severity were expressed per year and calculated as the total number of events over the follow-up exposure time. The CIs of the rate was computed using a model which accounts for repeated events. Respiratory pathogens NTHi and Mcat was determined by polymerase chain reaction (PCR) analysis in sputum samples.
Time frame: From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451)
Population: The analysis was performed on the Modified Total Vaccinated cohort, which includes all vaccinated subjects with 2 documented study vaccine administrations with respect to the vaccine actually administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3277511A Group | Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity | 0.39 exacerbations per person- year |
| Control Group | Rate of NTHi-associated and/ or Mcat-associated AECOPD of Any Severity | 0.35 exacerbations per person- year |