E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers above 25 years of age |
|
E.1.1.1 | Medical condition in easily understood language |
Healthy volunteers above 25 years of age |
|
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.
|
|
E.2.2 | Secondary objectives of the trial |
3.Compare levels of QIV and PCV13 vaccin induced antibody responses and persistence over time in older adults.
4.Compare PCV13 carrier protein-specific serum antibody titers pre- and post-PCV13 vaccination in older adults with the response in middle-aged adults and adults.
5.Compare influenza vaccine–specific and PCV13 carrier protein-specific T-cell responses pre- and post-vaccination in older adults with those observed in middle- aged adults and adults.
6.Determine the impact of clinical baseline status and changes in baseline status, as a predictive marker for vaccine response and compare them between older adults, middle-aged adults and adults.
7.Determine the impact of (immunological) biomarkers status at baseline as a predictive marker for vaccine response for each subject and compare results for older adults to middle-aged adults and adults.
|
|
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
|
|
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.
•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 pregnancy.
•Known to be positive for human immunodeficiency virus (HIV), and/or hepatitis C virus (HCV) and/or hepatitis B virus (HBV).
|
|
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.
•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.
|
|
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 |
|
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), 6 (T9) and 12 (T10) 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).
|
|
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, 18 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 |
|
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 |
|
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |