E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children aged 2-18 years (inclusive), with asthma / recurrent wheezing. |
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E.1.1.1 | Medical condition in easily understood language |
Children aged 2-18 years (inclusive), with asthma / recurrent wheezing. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic asthma |
E.1.2 | System Organ Class | 100000004855 |
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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 safe in children with "severe" asthma or recurrent wheezing?
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E.2.2 | Secondary objectives of the trial |
1) Is the intranasal LAIV influenza ('flu) vaccine effective in children? 2) Is it possible to predict those children with asthma who may be more likely to experience respiratory symptoms in the weeks following LAIV? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 2 – 18 years old
2. Physician diagnosis of asthma or recurrent wheezing (by the hospital specialist)
3. 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. Admission to PICU for respiratory illness in the preceding 2 years.
2. 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
3. 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. 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.
*Items 3b-3d are relative contra-indications: Many children with “difficult-to-control” symptoms may meet fail to meet these criteria on a routine basis. Where these are present, the study centre PIs are able to authorise participation on a case-by-case basis, after assessing the child and their lung function at the time of enrolment.
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.
Administration of another live vaccine (e.g. MMR) within the previous 4 weeks is no longer a contra-indication to LAIV administration, according to updated DoH guidelines.
NB: See Summary of Product Characteristics for full details of contra-indications to LAIV.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in symptom/disease control assessment through validated questionnaire pre- and 4 weeks after LAIV in children with asthma / recurrent wheezing: • In children age 2-4 years inclusive: TRACK score • In children age 5+ years: Asthma Control Test
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to the end of the influenza vaccination season (end Feb 2017) |
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E.5.2 | Secondary end point(s) |
1. Incidence of adverse events (AE) and serious adverse events (SAEs) in children receiving LAIV: • AEs occurring up to 72 hours after LAIV. • SAEs unrelated to asthma symptoms with onset up to 72 hours after LAIV • Incidence of a ‘significant exacerbation’ in asthma, defined as: i. At least 3 day course of oral steroids following an unscheduled contact with a healthcare professional; OR ii. Unscheduled visit to an Emergency department or admission to hospital for treatment of asthma symptoms, requiring systemic corticosteroids
2. Vaccine efficacy in the 2016/17 influenza season, through documentation of the incidence of laboratory confirmed influenza and other respiratory viruses in children receiving 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 4 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 | 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 | 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
| 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 | 14 |
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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End of surveillance period (approx May 2017) |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 20 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 20 |