| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy children will be immunised with two vaccines against influenza: Agrippal or Imuvac, or Fluad to study the immune responses to immunisation at a genetic level. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| 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 |
Infants and young children do not respond as well as adults to the flu vaccines currently available in the UK. Fluad, or ATIV is a different type of influenza vaccine has been available in the European continent for the last decade, and contains an adjuvant known as MF59.
This vaccine has been used extensively in adults, but is not yet licensed for use in
children. Previous studies have shown that it does produce an enhanced immune response in children compared with traditional vaccines (TIV), and that it is safe in this age group. However, the specific means by which MF59 influences the immune system are not fully characterised.
This study aims to assess the genes that are ‘switched on’ in response to immunisation with these two vaccines to better understand how the immune response to these vaccines differs.
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| E.2.2 | Secondary objectives of the trial |
o To assess the immune response to of TIV & ATIV in terms of the standard measure of influenze vaccine immunogenicity: the haemagglutination-Inhibition test (HAI). This will be performed for each of the three influenza strains contained in the vaccine (A/H1N1, A/H3N2, B), four weeks after completion of vaccination.
o To evaluate the reactogenicity & safety of ATIV in terms of local & systemic reactions following vaccination.
o To study the immune response to the TIV and ATIV vaccine in terms of specific B cells and T cells (types of lymphocytes or white blood cells)..
o To explore the relationship between gene expression and the T cell, B cell and HIA response to immunisation with TIV and ATIV.
o To explore the relationship between gene expression and the reactogenicity of TIV and ATIV.
|
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All of the following criteria need to be met to participate in the study:
1.The investigator believes that the parents / legal authorised representative(s) (LARs) of the child can and will comply with requirements of the protocol (e.g. completion of diary cards, understanding of study procedure, consent process, availability at visits)
2.Written informed consent obtained from parent / LAR (s) of the subject
3.Age from 14 months to 26 months (from start of 14 months up to & excluding 27 months of age)
4.Subject is healthy as determined by medical history and clinical examination
5.Has received standard UK immunisation schedule |
|
| E.4 | Principal exclusion criteria |
A participant cannot participate if any of the following criteria are met:
1. The child is in care
2. Use or planned use of any non-registered or investigational product in last 30 days
3. Previous influenza vaccination
4. Microbiologically proven influenza illness or treatment with antiviral medications
5. Confirmed or suspected egg allergy or allergic reaction to previous vaccinations.
6. Chronic serious medical conditions which may, in the opinion of the investigator, interfere with evaluation of study objectives e.g. Chronic lung disease, chronic liver/renal disease, chronic renal failure chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21).
7. Suspected or confirmed immunosuppressive or immunodeficiency conditions (including splenic dysfunction & HIV)
8. Autoimmune conditions e.g. Type 1/2 diabetes mellitus, thyroid disease, juvenile idiopathic arthritis etc.
9. Bleeding disorders |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To describe gene expression profiles of participants following immunisation with TIV or ATIV in relation to baseline profiles. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| To describe gene expression profile in response to TIV & ATIV vaccine at each time point. These would be at Day 0 (baseline), Day 29,31,35 (as per subgroup assigned following randomisation) and Day 56 |
|
| E.5.2 | Secondary end point(s) |
- To describe the immunogenicity of TIV & ATIV in terms of haemagglutination-Inhibition test (HAI) against each of the three vaccine strains (A/H1N1, A/H3N2, B), four weeks after completion of vaccination.
- To evaluate the reactogenicity & safety of ATIV in terms of local & systemic reactions following vaccination.
- To study T&B cell responses following immunisation with each vaccine.
- To explore the relationship between gene expression and the T cell, B cell and HIA response to immunisation with TIV and ATIV.
- To explore the relationship between gene expression and the reactogenicity of TIV and ATIV.
|
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity
- The percentage of subjects with HAI titres ≥ 1:40 measured at specific time points 4 weeks after two doses of TIV or ATIV (Seroconversion rate)
- Geometric Mean Titres (GMTs) of HAI at Day 0 & Day V2+ (26-35 days)
- Mean geometric increase in HAI titres at Day V2+1, V2+3, V2+7 & V2+28 (26-35).
- Frequency & phenotype of influenza antigen specific T cells using Intracellular Cytokine Staining or Elispot.
- Frequency of influenza antigen specific B cells by Elispot.
Reactogenicity
- Percentage of participants experiencing fever (≥ 38°C axillary),local tenderness, swelling or erythema within 8 days (Day 0 to Day 7) of each immunisation.
- Percentage of participants experiencing general symptoms within 8 days (Day 0 to Day 7)of each immunisation. |
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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 |
| gene expression following 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| 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 | 6 |
| 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
|
| The study will be considered ended when all the study visits have been completed and all the biological samples processed and analysed. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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