E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers above 25 years of age |
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E.1.1.1 | Medical condition in easily understood language |
Healthy volunteers above 25 years of age |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Compare serotype-specific IgG antibody response to pneumococcal PCV13 vaccination in older adults with the response in middle-aged adults and adults one month after vaccination. •Compare influenza vaccine strain-specific serum antibody titers in older adults with the response in middle-aged adults and adults one month after influenza vaccination.
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E.2.2 | Secondary objectives of the trial |
Comparison of age groups: QIV, PCV13 (total and protein-specific) and SARS-CoV-2 vaccine induced Ab responses protein-specific T-cell responses pre- and post-vaccination. Determine the impact of clinical baseline status and changes in baseline status, as a predictive marker for vaccine response. Determine the impact of (immunological) biomarkers status at baseline as a predictive marker for vaccine response for each subject. Kinetics and longevity of SARS-CoV-2 specific Ab subclasses and functionality induced by COVID-19 (booster) vaccination. Assessment of the magnitude, characteristics and longevity of the adaptive cellular response induced by the SARS-CoV-2 vaccine: activation, phenotype and function of vaccine-specific (effector, memory, regulatory) T-cells and B-cells.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Be 25 years or older at the time of inclusion. •Have received a seasonal influenza vaccination in previous season (2018-2019). •Be capacitated. •Have signed Informed Consent
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E.4 | Principal exclusion criteria |
•Having had a previous pneumococcal vaccination (PCV or the 23-valent pneumococcal polysaccharide vaccine (PPV23)). •Known or suspected allergy to any of the vaccine components or having experienced a previous severe adverse reaction to any vaccine. •Receipt of any high-dose (≥ 20 mg of prednisone daily or equivalent) daily corticosteroids (local incl. inhaled steroids are acceptable) within 2 weeks of study entry. •Repeated use of any high dose of corticosteroids (a dose of > 30 mg of prednisone or equivalent per day for multiple days) in the recent past. •Receipt of an organ- or bone marrow transplant •Have a (functional) asplenie. •Receipt of chemotherapy in the last 3 years. •Receipt of blood products or immunoglobulin, within three months of study entry. •Known or suspected coagulation disorder that in the opinion of the investigator would contraindicate against receiving an intramuscular injection or undergo frequent blood sampling. •Known anemia, measured as Hb < ( 8,5 mmol/l for men and 7,5 mmol/l for woman; NHG standard Anemia) •Known to be positive for human immunodeficiency virus (HIV), and/or hepatitis C virus (HCV) and/or hepatitis B virus (HBV).
Exclusion criteria COVID-19 vaccination study
• Treatment with COVID-19 monoclonal antibodies less that 3 months before COVID-19 vaccination. • Known pregnancy at the moment of COVID-19 vaccination.
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Pneumococcal serotype- specific serum IgG antibody concentrations (GMCs) pre-vaccination (T5) and one-month post (T8) PCV13 vaccination measured by bead-based multiplex immune assay. 2.Influenza vaccine strain-specific serum antibody titers (GMTs) will be measured pre- vaccination (T0) and one-month post-influenza vaccination (T4) by Hemagglutinin Inhibition (HI) assay.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 6 months and 7 months after start study 2. 1 month and 2 months after start of the study |
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E.5.2 | Secondary end point(s) |
1.Influenza strain-specific and pneumococcal serotype-specific antibody titers in serum pre- and post-vaccination: ((T1, T5, T3, T7, T4, T8, T5, T9, T10). 2.CRM197-specific serum antibody titers before (T5) and at 7 days (T7), 1 (T8) and 6 (T9) months post pneumococcal vaccination 3. Influenza-specific and CRM197-specific T-cells measured by Enzyme-Linked Immunosorbent Spot (ELISPOT) in peripheral blood mononuclear cells (PBMCs) of pre- (T0; T5) and post-vaccination samples (T3, T4, T7, T8). 4. A- health status assessment will be done by questionnaires, which include demographics, the short-form (SF) 36 health assessment of quality of life that covers 8 different sections (vitality, physical functioning, pain, general health perception, physical role functioning, emotional role functioning, social role functioning and mental health), a EQ-5D QoL-assessment, socio-economic status (SES), chronic diseases and medication use (including other vaccines), level of exercise, body mass index (BMI) and life style characteristics. In addition, grip strength and blood pressure will be measured by standardized protocols. Questionnaires and measurements will be done at 3 time points during the study at T0, T5 and T9. A deficit accumulation index will be calculated for each subject and the subjects will be ranked based on this index. 5. Measure absolute numbers of immune cell types, a.o. lymphocytes, granulocytes and monocytes, in whole blood by Trucount (T0, T5). Measure cell frequency, phenotype and functional capacity of immune cells by Fluorescence-Activated Cell Sorting (FACS). Measure priming efficacy of T-cells specific for influenza or model antigens. Measure systemic and local immune and inflammatory profiles by systems immunology, serology and molecular methods in serum, saliva and swabs. (T0, T5, T9). Determine biomarkers, such as creatinine and cystatin C in plasma. Determine both broad and targeted transcriptome profile at baseline (T0, T5). 6. Measure cell frequency, phenotype and functional capacity of SARS-CoV-2 specific immune cells by Fluorescence-Activated Cell Sorting (FACS). 7. SARS-CoV-2 specific IgG/IgA/IgM GMC in serum at baseline (T0), at day 28 following 1st dose, and at day 28, at 6 months and at 12 months after second vaccination and 28 days, 3, 6 and 12 months after booster COVID-19 vaccination, assessed by MIA. 8. SARS-CoV-2 specific vaccine-induced antibody neutralizing capacity, assessed by MIA as pseudoneutralization potential in all participants and assessed and validated in golden standard neutralization assay against various circulating SARS-CoV-2 genotypes in the subset of participants; at 28 days following completion of vaccination. 9. Phenotype and function (such as memory, follicular and regulatory) of SARS-CoV-2 specific T-cells by in vitro stimulation of PBMC with viral antigen followed by ELISpot, supernatant analysis for cytokines and Fluorescence-Activated Cell Sorting (FACS). 10. Phenotype and functional capacity of SARS-CoV-2 vaccine-specific memory B-cells, by in vitro stimulation of PBMC with viral antigen followed by ELISpot, supernatant analysis for secreted antibodies and FACS. 11. Ig (A1/A2/G) GMC in saliva and/or nasal lining fluid measured at 28 days following completion of vaccination, compared to baseline (Ta or if no Ta available T9).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. month 1, 2, 6, 7, 12 and 18 after start study 2. month 6, 7, 12 after start study 3. month 0, 2, 6, 7 after start study 4. month 0, 6 and 12 after start study 5. month 0, 6 and 12 after start study 7. before and 28 days after 1st dose, 28 days, 6 and 12 month after 2nd dose and 28 days,3, 6 and 12 months after booster dose 8. 28 days after second dose; 28 days after booster dose 11. before 1st dose and 28 days after 2nd dose; 28 days after booster dose
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
immune responses after influenza and pneumococcal vaccination |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |