E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children aged 2-18 years (inclusive), some of whom will have asthma and/or food allergies. |
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E.1.1.1 | Medical condition in easily understood language |
Children aged 2-18 years (inclusive), some of whom will have asthma and/or food allergies. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001738 |
E.1.2 | Term | Allergy |
E.1.2 | System Organ Class | 100000004870 |
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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 |
Is the intranasal LAIV influenza ('flu) vaccine effective in children?
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E.2.2 | Secondary objectives of the trial |
1) Do laboratory tests (both blood test and a nasal swab) correlate with vaccine effectiveness? 2) Is the intranasal LAIV influenza ('flu) vaccine effective and safe in children, including those with asthma / a history of recurrent wheezing? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 2 – 18 years.
2. Written informed consent from parent/guardian (or the patient themselves from age 16 years), with assent from children aged 8 years and above wherever possible.
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E.4 | Principal exclusion criteria |
1. Contraindications to LAIV (notwithstanding allergy to egg protein), which include:
a. Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue) b. Previous systemic allergic reaction to LAIV c. Previous allergic reaction to an influenza vaccine (not LAIV) is a relative contra-indication, which must be discussed with the site PI to confirm patient suitability d. Children/adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids*. *High-dose steroids is defined as a treatment course for at least one month, equivalent to a dose of prednisolone at 20mg or more per day (any age); or for children under 20kg, a dose of 1mg/kg/day or more.
NB: LAIV is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled/low-dose oral systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.
e. Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection. f. pregnancy
2. Contraindication to vaccination on that occasion, e.g. due to child being acutely unwell:
a. Febrile ≥38.0oC in last 72 hours b. Acute wheeze in last 72 hours requiring treatment beyond that normally prescribed for regular use by the child’s treating healthcare professional c. Recent admission to hospital in last 2 weeks for acute asthma d. Current oral steroid for asthma exacerbation or course completed within last 2 weeks e. Received any blood or blood products within the past 12 weeks f. Any other significant condition or circumstance which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.
Recent antihistamine use is not a contra-indication to LAIV administration, but use of any antihistamine in the 96 hours prior to LAIV will be logged on the CRF.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of laboratory confirmed influenza and other respiratory viruses in participants receiving LAIV, compared to their unvaccinated sibling controls. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to the end of the influenza season (end March 2016) |
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E.5.2 | Secondary end point(s) |
1. Immune response to vaccine and non-vaccine influenza strains before and after a single dose of LAIV administration, with respect to i. serological measures, including: • Geometric mean titre. GMTs (with 95% confidence intervals) for HI (H3N2, H1N1, H7N9, B) and MN (H1N1 and H7N9) prior to and 3-6 weeks post LAIV (pre and post bleed); • Geometric Mean Ratio. GMRs (95% CI) will be calculated for the HI, MN results (for all viruses) for post bleed / pre bleed (day 0) sample; • Percentages of subjects with Seroconversion or Significant Increase in HI and MN Titre. Seroconversions or significant increase (negative titres at D0; <10 and ≥ 40 at D21 or at least 4-fold increase in titre) in HI titres or MN (for all viruses) from pre-immunization to 3-6 weeks post LAIV (pre and post bleed); • Percentages of subjects achieving each of the following thresholds: HI ≥ 40, MN ≥ 40; MN ≥ 80, four-fold rise in MN titres: The number and proportion of subjects achieving each threshold prior to and 3-6 weeks post LAIV (pre and post bleed) will be tabulated for all viruses. ii. Change in specific nasal IgA responses prior to and 3-6 weeks post LAIV (and how these correlate to the above serological measures)
with sub-analyses according to whether participants have received prior vaccination with pandemic influenza vaccine / LAIV / both.
2. To monitor for incidence of adverse events (AE) and serious adverse events (SAEs) in children receiving LAIV, with the following sub-analyses: • AEs occurring up to 72 hours after LAIV in participants with a history of atopy / asthma / recurrent wheezing, compared to non-atopic participants. • Wheezing / asthma symptoms in subjects given LAIV who have a past medical history of asthma or recurrent wheeze in the 4 weeks prior to vaccine administration vs the four weeks after LAIV.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Delayed events will be assessed by telephone follow-up within 4-7 days of vaccination. Asthma control will be assessed by validated questionnaire pre and 3-4 weeks post LAIV. Immune responses to vaccine will be assessed pre and 3-6 weeks post LAIV. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
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 | No |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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For intervention phase: LVLS For overall trial: end of surveillance period (end of March 2016) |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 | 18 |