Clinical Trial Results:
A phase II, multi-centre, open labelled randomised control trial to describe immune & transcriptomic responses to trivalent inactivated vaccine (TIV) & MF59 adjuvanted influenza vaccine (ATIV) in 14 -26 month healthy children.
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Summary
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EudraCT number |
2012-002443-26 |
Trial protocol |
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Global end of trial date |
21 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Aug 2016
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First version publication date |
24 Aug 2016
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Other versions |
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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 |
OVG2012/04
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01682369 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Oxford Vaccine Group
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Sponsor organisation address |
CCTVM, Churchill Hospital, Old Road, Headington, Oxford, United Kingdom, OX3 7LE
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Public contact |
Professor Andrew J Pollard, University of Oxford, 44 01865857420, andrew.pollard@paediatrics.ox.ac.uk
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Scientific contact |
Professor Andrew J Pollard, University of Oxford, 44 01865857420, andrew.pollard@paediatrics.ox.ac.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 |
21 Nov 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Nov 2014
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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 |
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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Protection of trial subjects |
Ethical, Legal and Management Protection: Every effort was made to ensure that parents or guardians giving informed consent were able to understand fully the nature of the study including the risks, burdens, benefits and implications that taking part had for their child. The study involved the collection of three blood samples that would not normally be part of routine care. In order to minimise any discomfort, local anaesthetic cream was offered to numb the skin prior to the sample being collected. The members of the study team undertaking venepuncture had specific training and experience in this technique. With the parent/guardians agreement two attempts at blood sampling were made and if unsuccessful a further visit was arranged by the study team.
Strict inclusion and exclusion criteria applied to the enrolment of each study participant.
The study complied with the Data Protection Act which requires data to be anonymised as soon as it is practical to do so ensuring that the participant's anonymity was maintained throughout the trial.
This is a descriptive study to understand how genetic responses vary at different times following immunisation with two different influenza vaccines. Participants had the advantage of receiving one of the influenza vaccines, which is not part of their routine schedule. Participant involvement will help us to understand these responses and plan future vaccine development.
Participants could withdraw from the study at any time.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2012
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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: 90
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Worldwide total number of subjects |
90
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EEA total number of subjects |
90
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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) |
90
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Children (2-11 years) |
0
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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 |
Study participants were identified within the local area who were of the appropriate age range via the Child Health Computer Database (CHCH) and/or the National Health Applications and Infrastructure Services (NHAIS) who hold the central NHS patient database. Recruitment was also active via the Oxford Vaccine Group study website. | |||||||||
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Pre-assignment
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Screening details |
Explanation for the study, obtain written informed consent parent/guardian, randomise/assign participant number, check exclusion/inclusion criteria, physical examination, measure/record axillary temperature, collect blood sample (up to 6.0ml), administer dose (0.25ml) of TIV or ATIV vaccine, observe for 15 mins, issue ruler/thermometer/diary card. | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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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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TIV (Group 1) | |||||||||
Arm description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the TIV vaccine with variable visit windows for blood collection at Visit 3 defined as 1A, 1B and 1C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 1A (V2 +1), 1B (V2+3) and 1C (V2+7) blood test V4 = V2 + 28 days (blood test) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
TIV (AGRIPPAL®/BEGRIPAL®)
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Investigational medicinal product code |
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Other name |
trivalent inactivated vaccine (TIV)
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
2 x 0.25ml dose administered at an interval of 26-35 days.
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Arm title
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ATIV (Group 2) | |||||||||
Arm description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the ATIV vaccine with variable visit windows for blood collection at Visit 3 defined as 2A, 2B and 2C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 2A (V2 +1), 2B (V2+3) and 2C (V2+7) blood test V4 = V2 + 28 days (blood test) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
ATIV (IMUVAC®)
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Investigational medicinal product code |
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Other name |
adjuvanted influenza vaccine (ATIV)
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
2 x 0.25ml dose administered at an interval of 26-35 days.
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Baseline characteristics reporting groups
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Reporting group title |
TIV (Group 1)
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Reporting group description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the TIV vaccine with variable visit windows for blood collection at Visit 3 defined as 1A, 1B and 1C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 1A (V2 +1), 1B (V2+3) and 1C (V2+7) blood test V4 = V2 + 28 days (blood test) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ATIV (Group 2)
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Reporting group description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the ATIV vaccine with variable visit windows for blood collection at Visit 3 defined as 2A, 2B and 2C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 2A (V2 +1), 2B (V2+3) and 2C (V2+7) blood test V4 = V2 + 28 days (blood test) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Data Analysis - TIV
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Humoral immunity to influenza (HAI titres), multicytokine production, ELISPOT and transcriptome analysis on blood samples collected at V1, V2, V3 and V4.
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Subject analysis set title |
Data Analysis - ATIV
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Humoral immunity to influenza (HAI titres), multicytokine production, ELISPOT and transcriptome analysis on blood samples collected at V1, V2, V3 and V4.
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End points reporting groups
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Reporting group title |
TIV (Group 1)
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Reporting group description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the TIV vaccine with variable visit windows for blood collection at Visit 3 defined as 1A, 1B and 1C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 1A (V2 +1), 1B (V2+3) and 1C (V2+7) blood test V4 = V2 + 28 days (blood test) | ||
Reporting group title |
ATIV (Group 2)
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Reporting group description |
Participants were randomised 1:1:1 into 3 groups (n=15 per group) to receive the ATIV vaccine with variable visit windows for blood collection at Visit 3 defined as 2A, 2B and 2C. V1 = Day 0 (blood test at baseline + vaccination 1st dose) V2 = Day 28 (vaccination 2nd dose) V3 = 2A (V2 +1), 2B (V2+3) and 2C (V2+7) blood test V4 = V2 + 28 days (blood test) | ||
Subject analysis set title |
Data Analysis - TIV
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Humoral immunity to influenza (HAI titres), multicytokine production, ELISPOT and transcriptome analysis on blood samples collected at V1, V2, V3 and V4.
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Subject analysis set title |
Data Analysis - ATIV
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Humoral immunity to influenza (HAI titres), multicytokine production, ELISPOT and transcriptome analysis on blood samples collected at V1, V2, V3 and V4.
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End point title |
Study Objectives [1] | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
To describe gene expression profile in response to TIV & ATIV vaccine at each time point.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the descriptive nature of the study, formal statistical analysis comparing the two groups has not be performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All AEs occurring in the first 8 days after immunisation (Day 0 to Day 7), and all AEs resulting in an unscheduled visits to a physician or emergency department or withdrawal from the study occurring within 1 month after vaccination.
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Adverse event reporting additional description |
All AEs occurring in the first 8 days after immunisation (Day 0 to Day 7), and all AEs resulting in an unscheduled visits to a physician or emergency department or withdrawal from the study occurring within 1 month after vaccination observed by the investigator or reported by the participant’s parent or guardian, whether or not attributed to study
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
Protocol | |||||||||||||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
TIV (Group 1)
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Reporting group description |
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Reporting group title |
ATIV (Group 2)
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Reporting group description |
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| 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: Non-serious adverse events were recorded only as a secondary objective and are not expected to contribute to future safety evaluations of this vaccine. Therefore non-serious adverse events are not listed in this submission. |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||
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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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07 Nov 2012 |
Substantial Amendment 1: the amendment covered a change to V2.0 of the protocol because of on-going difficulties sourcing the control TIV vaccine Agrippal. The Protocol has been amended to allow for the possibility of an additional control vaccine (Imuvac), depending on vaccine availability at the start of enrolment. In addition a further information booklet and Health professional letter has been created to explain the study with use of the Imuvac vaccine. A letter/ Compliments slip has also been created to explain the changes to parents.
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/26755593 |
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