Clinical Trial Results:
A Phase III, Randomized, Observer Blind, Multicenter Study to Evaluate the Safety and Immunogenicity of Repeated Exposure to an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV), Administered to Subjects Previously Vaccinated in Trial V118_05
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Summary
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EudraCT number |
2014-002599-95 |
Trial protocol |
FI |
Global end of trial date |
13 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Sep 2017
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First version publication date |
27 Sep 2017
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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 |
V118_05E1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02255409 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Seqirus UK Limited
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Sponsor organisation address |
The Point, 29 Market Street, Maidenhead, United Kingdom, SL6 8AA
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Public contact |
Clinical Trial Disclosure Manager, Seqirus, Seqirus.Clinicaltrials@seqirus.com
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Scientific contact |
Clinical Trial Disclosure Manager, Seqirus, Seqirus.Clinicaltrials@seqirus.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001715-PIP01-14 | ||
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 Jan 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jan 2016
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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 |
Primary Immunogenicity Objective: To evaluate the antibody responses to homologous
(CBER criteria) influenza strains post vaccination with aQIV or a non-adjuvanted
comparator influenza vaccine in children previously vaccinated in parent trial V118_05.
Primary Safety Objective: To evaluate the safety of revaccination of aQIV or nonadjuvanted
comparator vaccine in children previously vaccinated in parent trial V118_05
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Protection of trial subjects |
This clinical study was designed and was to be implemented and reported in accordance with the
International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP),
with applicable local regulations including European Directive 2001/20/EC, US Code of Federal
Regulations (CFR) Title 21, and Japanese Ministry of Health, Labor, and Welfare, sponsor codes on
protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki
European Council 2001, US CFR, ICH 1997).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Sep 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
12 Months | ||
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 |
Finland: 100
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Country: Number of subjects enrolled |
United States: 507
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Worldwide total number of subjects |
607
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EEA total number of subjects |
100
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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) |
101
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Children (2-11 years) |
506
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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 |
Subjects were enrolled from 30 sites in 2 countries | |||||||||||||||||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in the trial | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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aQIV | |||||||||||||||||||||
Arm description |
Subjects approximately ≥12 months to 7 years of age who had received aQIV in the parent study V118_05 received aQIV in the present study V118_05E1. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Adjuvanted Quadrivalent Influenza Vaccine (aQIV) -surface antigen, inactivated, adjuvanted with MF59
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
IM/0.5ml (0.25 mL for subjects <36 months)
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Arm title
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Comparator QIV | |||||||||||||||||||||
Arm description |
Subjects approximately ≥12 months to 7 years of age who had received TIV/QIV in the parent study V118_05 received QIV in the present study V118_05E1. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Inactivated Quadrivalent Influenza Virus Vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
IM/0.5ml (0.25 mL for subjects <36 months)
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Baseline characteristics reporting groups
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Reporting group title |
aQIV
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Reporting group description |
Subjects approximately ≥12 months to 7 years of age who had received aQIV in the parent study V118_05 received aQIV in the present study V118_05E1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparator QIV
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Reporting group description |
Subjects approximately ≥12 months to 7 years of age who had received TIV/QIV in the parent study V118_05 received QIV in the present study V118_05E1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
aQIV
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Reporting group description |
Subjects approximately ≥12 months to 7 years of age who had received aQIV in the parent study V118_05 received aQIV in the present study V118_05E1. | ||
Reporting group title |
Comparator QIV
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Reporting group description |
Subjects approximately ≥12 months to 7 years of age who had received TIV/QIV in the parent study V118_05 received QIV in the present study V118_05E1. | ||
Subject analysis set title |
Full Analysis Set - Homologous
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects in the Enrolled Set, who received a study vaccination and provided evaluable
serum samples against vaccine strains for both before (baseline) and after vaccination.
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Subject analysis set title |
Full Analysis Set - Heterologous
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects in the Enrolled Set, who received a study vaccination and provided evaluable
serum samples against heterologous strains for both before (baseline) and after vaccination.
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End point title |
Immunogenicity Endpoint: Percentage of subjects achieving seroconversion - Homologous Strains (Day 22) [1] | ||||||||||||||||||||||||
End point description |
Antibody responses assessed in terms of percentage of subjects achieving seroconversion at 21 days after vaccination against vaccine strains.
Seroconversion is defined as HI ≥1:40 for subjects negative at baseline (ie, HI titer <1:10); or a minimum 4-fold increase in HI titer for subjects positive at baseline (ie, HI titer HI ≥1:10).
The immunogenicity responses of the study vaccines were evaluated following measurements established by the current CBER criteria for the pediatric population. The CBER criteria were met if the lower bound of the 2-sided 95% CI for the percent of subjects achieving SC for HI antibody met or exceeded 40%
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End point type |
Primary
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End point timeframe |
21 days after vaccination
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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: The analysis of the primary endpoint was descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Immunogenicity Endpoint: Percentage of subjects achieving HI titer ≥ 1:40 - Homologous Strains (Day 22) [2] | ||||||||||||||||||||||||
End point description |
Antibody responses assessed in terms of percentage of subjects achieving HI titer ≥1:40 at 21 days after vaccination against vaccine strains.
The immunogenicity responses of the study vaccines were evaluated following measurements established by the current CBER criteria for the pediatric population. The CBER criteria were met if the lower bound of the 2-sided 95% CI for the percent of subjects achieving an HI titer ≥1:40 met or exceeded 70%.
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End point type |
Primary
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End point timeframe |
21 days after vaccination
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| Notes [2] - 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: The analysis of the primary endpoint was descriptive. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Safety Endpoint: Subjects reporting SAEs, AEs leading to withdrawal from the study, new onset of chronic diseases (NOCD), adverse events of special interest (AESI) and medically attended AEs [3] | |||||||||||||||||||||||||||
End point description |
Safety was assessed in terms of number of subjects reporting SAEs, AEs leading to withdrawal, NOCDs, AESI and medically attended AEs.
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End point type |
Primary
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End point timeframe |
Up to 12 months after vaccination
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| Notes [3] - 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: The analysis of the primary endpoint was descriptive. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Safety Endpoint: Subjects with solicited local and systemic AEs and other solicited data | |||||||||||||||||||||
End point description |
Safety was assessed in terms of percentage of subjects reporting solicited local and systemic adverse events following vaccination.
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End point type |
Secondary
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End point timeframe |
7 days following vaccination
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Immunogenicity Endpoint: Geometric Mean Titers Ratios - Homologous Strains (Day 22) | ||||||||||||||||
End point description |
GMT Ratio: aQIV (GMT) over QIV (GMT)
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End point type |
Secondary
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End point timeframe |
21 days after vaccination
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| Notes [4] - aQIV N=309, QIV N=273 |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Immunogenicity Endpoint: Geometric Mean Titers Ratios - Heterologous Strains (Day 22) | ||||||||||||
End point description |
GMT Ratio: aQIV (GMT) over QIV (GMT)
Heterologous strains tested: A/H3N2 is Influenza A H3N2 Hong Kong/2014 Ab; B/Yamagata is Influenza
B/Phuket/2013 Ab
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End point type |
Secondary
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End point timeframe |
21 days after vaccination
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| Notes [5] - aQIV N=155, QIV N=138 |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 through Day366
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Adverse event reporting additional description |
Solicited local and systemic AEs were reported from day 1 through day 7 after vaccination. All unsolicited AEs were captured through day 22. SAEs, AEs leading to withdrawal, NOCDs, AESIs were captured from day 1 through day 366
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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 |
19.1
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Reporting groups
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Reporting group title |
aQIV
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Reporting group description |
Subjects approximately ≥12 months to 7 years of age who had received aQIV in the parent trial received aQIV in the present study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Comparator QIV
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Reporting group description |
Subjects ≥12 months to 7 years of age who had received a comparator non adjuvanted TIV/QIV in the parent study V118_05 received a non adjuvanted QIV in the present study V118_05E1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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29 Jul 2014 |
- The immunogenicity endpoints were updated to include secondary immunogenicity endpoints at Day 181. The percentage of subjects achieving seroconversion and HI titer ≥1:40 at Day 181 were included as additional secondary immunogenicity endpoints.
- Secondary objectives were updated to clarify that the 2 vaccine groups would be compared with regard to antibody response to homologous and heterologous influenza strains for the following endpoints: GMT, GMR (Day 22:Day 1), percentage of subjects achieving seroconversion, and percentage of subjects achieving HI titer ≥1:40.
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27 Oct 2014 |
- Text was added throughout the protocol to provide clarity on what information regarding influenza high risk status should be collected and the analysis to be conducted using this data.
- The Medically Attended Adverse Events section was added to provide clarity on definition of medically attended AEs, where and when they should be recorded. |
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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 | |||
