Clinical Trial Results:
A phase III/IV open-label study of the immunogenicity and safety of a single dose of a Live Attenuated Influenza Vaccine (LAIV) (FluenzTM) for each of three successive years in children naïve to, or in previous receipt of the AS03B adjuvanted H1N1 (2009) influenza vaccine (Pandemrix ™).
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Summary
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EudraCT number |
2013-003592-35 |
Trial protocol |
GB |
Global end of trial date |
31 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Feb 2019
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First version publication date |
07 Feb 2019
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Other versions |
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Summary report(s) |
Responses to live attenduated flu vaccine in children vaccinated previously with Pandremix |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LAIV Immuno
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02143882 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
LAIV IMMUNO: LAIN IMMUNO | ||
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Sponsors
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Sponsor organisation name |
Public Health England
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Sponsor organisation address |
Wellington House , London , United Kingdom, SE1 8UG
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Public contact |
Elizabeth Coates
elizabeth.coates@phe.gov.uk, Public Health England
Wellington House, London SE1 8UG, +44 0208 327 6084, elizabeth.coates@phe.gov.uk
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Scientific contact |
Elizabeth Coates
elizabeth.coates@phe.gov.uk, Public Health England
Wellington House, London SE1 8UG, +44 0208 327 6084, elizabeth.coates@phe.gov.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Mar 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Technical version:
To compare the immune response to homologous and heterologous strains before and after to annual doses of LAIV over three consecutive years in children aged 4-9(+364days) years at enrollment in naïve children vs those in previous receipt of the AS03B adjuvanted pandemic influenza vaccine to homologous vaccine strains .
Lay version:
To compare the immune system responses to various strains of flu after having the nasal influenza vaccine (LAIV) for each of three consecutive years in children aged 4-8 when they join the study and who have either previously had a dose of Pandemirix (a pandemic flu vaccine) or have never had any pandemic flu vaccine.
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Protection of trial subjects |
Parents will remain at the study visit location for at least 10 minutes after vaccination to be observed by the VRN for any immediate reactions.
Reactogenicity and short term safety will be assessed in several ways.
Parents/guardians will be instructed to inform the VRN if their child is unwell or if they visit a GP or the hospital during the study duration. Health diaries will be completed from the day of vaccination until seven days after vaccination. Staff will engage in active surveillance of study participants through a telephone interview on day 8 following immunisation. On day 21 staff will collect the health diary and make further enquiry about the child's health. GPs will be asked to let the VRN know if the child becomes ill or needs care by the GP or hospital.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Sep 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 254
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Worldwide total number of subjects |
254
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EEA total number of subjects |
254
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
254
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Healthy UK children (age range 4-9 years) who have previously received Pandremix vaccine or who are naive to pandemic influenza vaccine, who are eligible to receive LAIV. | |||||||||
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Pre-assignment
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Screening details |
Healthy UK children (age range 4-9 years) who have previously received Pandremix vaccine or who are naive to pandemic influenza vaccine, who are eligible to receive LAIV. | |||||||||
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Period 1
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Period 1 title |
Overall trial period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ARM1 | |||||||||
Arm description |
Previously vaccinated with pandemrix | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
LAIV
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour, liquid
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Routes of administration |
Inhalation use
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Dosage and administration details |
0.2ml
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Arm title
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ARM2 | |||||||||
Arm description |
Naiive to pandemrix | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
LAIV
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation vapour, liquid
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Routes of administration |
Inhalation use
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Dosage and administration details |
0.2ml
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Baseline characteristics reporting groups
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Reporting group title |
ARM1
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Reporting group description |
Previously vaccinated with pandemrix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ARM2
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Reporting group description |
Naiive to pandemrix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ARM1
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Reporting group description |
Previously vaccinated with pandemrix | ||
Reporting group title |
ARM2
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Reporting group description |
Naiive to pandemrix | ||
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End point title |
Proportion seroconverting to H1N1 | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Within three weeks of vaccination
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Statistical analysis title |
Pre planned | |||||||||
Comparison groups |
ARM1 v ARM2
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Number of subjects included in analysis |
254
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Between recruitment and three weeks after last dose
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
ARM1
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Reporting group description |
- | ||||||||||||||||||||||||||||||
Reporting group title |
ARM2
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Reporting group description |
- | ||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: This was an immunogenicity study and not a reactogenicity study. |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Jun 2014 |
Staff changes:
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Methodology changes:
Addition of assessment of cell mediated immune (CMI) responses through collection of a further 5ml of blood from up to 100 in each group of 9 and 10 year olds – information added in background, summary, objectives, testing of samples and in the patient information sheet and consent form.
References:
Addition of three extra references with regard to the addition of the CMI work.
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08 Dec 2014 |
Addition of nasal swabs in the event of influenza symptoms in children enrolled in the Sniffle2 study (REC ref 14/WM/0159, NRES
Committee West Midlands --‐Edgbaston)
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22 May 2015 |
Extension of recruitment period into year 2 of the study due to late availability of vaccine in year 1 meaning target of 500 not reached. Planned end date of study remains unchanged i.e. year 2 recruits only participate for two years. This amendment therefore contains amended patient leaflets and consent forms for this purpose.
For existing participants in the main study a letter of thanks and a study update is included. All participants in Herts aged 9 years or over in years 2 and 3 will be invited to participate in the optional CMI testing using previously approved information and consent forms. Wording has been updated to reflect this.
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21 Jul 2015 |
Addition of nasal swabs in any children living in the same house as the vaccinated child in the event of influenza like illness (ILI). |
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18 Aug 2015 |
Addition of one box on the consent form for sibling swabbing to say the parent will only proceed if the child agrees at the time of the swab. |
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08 Jan 2016 |
Addition of the option of home visits |
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12 Aug 2016 |
Amendment of the schedule for collection of nose swabs for the third year of the study (autumn 2016 – Spring 2017) from whenever children have flu like symptoms to the days following vaccination – up to three swabs in the following week. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
