E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This trial is investigating healthy children and adult's gene expression and immune response to the Fluad (MF59)-adjuvanted trivalent influenza vaccine and also comparing these to the local and general reactions following vaccine administration. Healthy children will be immunised with 2 doses, adult with 1 dose. |
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E.1.1.1 | Medical condition in easily understood language |
This study aims to investigate healthy children and adult's immune responses to a different influenza vaccine, and further explore how the body's genes lead to this immune response. |
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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 |
The principal research objective of this study is to identify the specific ‘immune response’ genes which are activated by the ATIV vaccine and to correlate them to the immune response (level of antibodies - these are specific proteins against a virus which are part of the immune response) which occur when these genes are ‘switched on’ (this is also called gene expression). We are interested to assess the difference between the response in children (aged 13-24 months) compared to adults (aged 18 -65 years).
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E.2.2 | Secondary objectives of the trial |
The secondary objectives include: 1. To compare the gene response to different types of white blood cell response 2. To look at how good an immune response the body makes to the 3 individual strains of flu that are included in the flu vaccine. 3. To look at how the immune response correlates with any physical reactions to the vaccine (including local reactions - ie. redness/swelling/tenderness at the injection site, and general reactions including fever/irritability/poor feeding etc) 4. To compare the above local and general reactions to gene response/expression 5. To particularly compare the results above in children compared to adults in the early phase following the vaccine (in the first 3 days). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Children: •The investigator believes that the parents / LAR (s) of the child can and will comply with requirements of the protocol (e.g. completion of electronic diary, understanding of study procedure, consent process, availability at visits) and have internet access for the duration of the study. •Written informed consent obtained from parent / LAR (s) of the subject •Age from 13 months up to 24 months (excluding 24 months + 0 days and older) at time of V1 (first immunisation visit) •Born to two caucasian parents •Participant is healthy as determined by medical history and clinical examination •Have received all the vaccines specified in the UK immunisation schedule
Adults: •Written and informed consent obtained from participant •Age 18 years to 65 years (excluding 65 years +0 days and older) •Caucasian •Participant has internet access for the duration of the study •Participant is healthy as determined by medical history and clinical examination
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E.4 | Principal exclusion criteria |
Children •Child in care •Use (or planned use) of any non-registered or investigational product in last 30 days •Previous influenza vaccination •Microbiologically proven influenza illness or treatment with antiviral medications •Confirmed or suspected egg allergy •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). •Recommended for influenza vaccine in UK (eg. Children in clinical risk groups as specified by Public Health England) •Suspected or confirmed immunosuppressive or immunodeficiency conditions (including splenic dysfunction & HIV) •Autoimmune conditions e.g. Type 1/2 diabetes mellitus, thyroid disease, juvenile idiopathic arthritis etc •Bleeding disorders
Adults •Use (or planned use) of any non-registered or investigational product in last 30 days •Confirmed or suspected egg allergy •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 •Prior receipt of the 2015/2016 influenza vaccine •Recommended for influenza vaccine in UK (eg. in clinical risk groups as specified by Public Health England) •Suspected or confirmed immunosuppressive or immunodeficiency conditions (including splenic dysfunction & HIV) •Autoimmune conditions e.g. Type 1/2 diabetes mellitus, thyroid disease, juvenile idiopathic arthritis etc •Bleeding disorders •Pregnancy
Temporary Delay to first study intervention (children and adults)
• Participants who have experienced fever (≥38.0°C) or coryzal symptoms within the 24 hours prior to first study intervention • Use of systemic steroids for more than 1 week e.g. prednisolone >0.5mg/kg/day in the 3 months prior to first study intervention • Chronic administration (≥14 days in total) of immunosuppresants or other immune modifying drugs in the 3 months prior to first study intervention • Immunisation with inactivated vaccines within the week prior to first study intervention, or live vaccines within the 3 weeks prior to first study intervention • Receipt of blood, blood products and/or plasma derivatives or any immunoglobulin preparation in the 3 months prior to first study intervention • Receipt of antipyretics within 6 hours prior to immunization
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for this study will be the differential gene expression response to priming and boosting with ATIV and correlating these with haemagglutination inhibition (HAI) titers. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Differential gene expression at baseline (day -7 to day 0) and days 1, 3, 28, 29, 31 (ie. 1 and 3 days post each vaccine dose and day of 2nd dose). HAI titres will be performed at baseline (day -7 to day 0) and days 28 (day of second dose of ATIV) and 56 (28 days after 2nd dose). |
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E.5.2 | Secondary end point(s) |
The secondary objectives include: 1. To compare the gene response to different types of immune cell response 2. To look at how good an immune response the body makes to the 3 individual strains of flu that are included in the flu vaccine. 3. To particularly compare the immune response in children compared to adults in the early phase following the vaccine (in the first 3 days). 4. To look at how the immune response correlates with any physical reactions to the vaccine (including local reactions - ie. redness/swelling/tenderness at the injection site, and general reactions including fever/irritability/poor feeding etc) 5. To compare the above local and general reactions to gene response/expression
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The timepoints of secondary end points 1. Blood samples for gene expression and immune cell response at baseline (day -7 to 0), days 1, 3, 28, 29, 31 (ie. baseline, days 1 and 3 after each vaccine dose) 2. Blood samples looking at haemagglutination inhibition (HAI) titres at baseline, and day 56 (for children) or day 28 (for adults). 3. Blood samples for gene expression and innate immune cell response on day 1, 3, 29, and 31 in adults and children. 4 and 5:Blood samples (for gene and immune response) and electronic diary (local and general reactions) recordings for day of vaccination and 3 days following vaccine 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 |
Gene expression following 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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Yes |
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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The study will be considered ended when all the study visits have been completed and all the biological samples processed and analysed. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 26 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 26 |