Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| Secondary |
Number of Subjects Reported With Each Solicited Local Adverse Event (AE) |
Assessed solicited local symptoms were pain, redness and swelling |
During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61 |
|
| 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. |
During the 7-day follow-up period (the day of vaccination + 6 days) after each vaccination administered approximately at Day 1 and Day 61 |
|
| 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. |
During the 30-day follow-up period (the day of vaccination + 29 days) after each vaccination administered approximately at Day 1 and Day 61 |
|
| 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. |
From first vaccination (Day 1) up to Study end (at Day 451) |
|
| 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 |
From first vaccination (Day 1) up to Study end (at Day 451) |
|
| 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. |
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) |
|
| 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. |
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) |
|
| 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. |
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) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| Secondary |
Number of Days With AECOPDs of Any Severity |
The length of each AECOPDs was tabulated and presented via descriptive statistics (mean, Standard Deviation). |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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). |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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 |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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. |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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). |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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). |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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). |
From 1-month post-Dose 2 (at Day 91) up to study end (at Day 451) |
|
| 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.) |
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 |
|
| 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. |
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 |
|
| 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. |
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 |
|
| 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. |
At Day 1, Day 31, Day 61, Day 91, Day 271 and at Day 451 |
|
| 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-?), tumour necrosis factor-alpha (TNF-a) and cluster of differentiation 40 ligand (CD40L) are evaluated by flow cytometry and expressed as mean and standard deviation. |
At Day 1, Day 91, Day 271 and at Day 451 |
|
| 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-?, TNF-a and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
At Day 1, Day 91, Day 271 and at Day 451 |
|
| 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-?, TNF-a and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
At Day 1, Day 91, Day 271 and at Day 451 |
|
| 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-?, TNF-a and CD40L are evaluated by flow cytometry and expressed as mean and standard deviation. |
At Day 1, Day 91, Day 271 and at Day 451 |
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