Clinical Trial Results:
Immunogenicity, Reactogenicity and Safety of the Trivalent Influenza Subunit Vaccine Influvac® for the Northern Hemisphere Season 2013/2014. An Open-Label, Baseline-Controlled Study in Two Age Groups: Adult Subjects ≥ 18 and ≤ 60 Years and Elderly Subjects ≥ 61 Years of Age.
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Summary
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EudraCT number |
2013-000881-12 |
Trial protocol |
DE BE |
Global end of trial date |
03 Aug 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Aug 2019
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First version publication date |
15 Aug 2019
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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 |
M13-998
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Abbott Biologicals B.V
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Sponsor organisation address |
C.J. van Houtenlaan 36, CP Weesp, Netherlands, NL-1381
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Public contact |
Public Affairs Manager, Abbott Products Operations AG, hind.ounis@abbott.com
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Scientific contact |
Global Clinical Director, Abbott Healthcare Products B.V., serge.vandewitte@abbott.com
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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 |
03 Aug 2013
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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 |
03 Aug 2013
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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 |
The primary objective of this study was to determine the immunogenicity of the trivalent influenza subunit vaccine Influvac® for the northern hemisphere season 2013/2014, three weeks after vaccination according to the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance on Harmonization of Requirements for Influenza Vaccines (CPMP/BWP/214/96) in two groups: adults aged ≥ 18 and ≤ 60 years and elderly ≥ 61 years of age.
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Protection of trial subjects |
The study was conducted in compliance with Good Clinical Practice and the applicable national regulations so as to assure that the rights, safety, and well being of the participating study subjects were protected consistent with the ethical principles that have their origin in the Declaration of Helsinki.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Jul 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 |
Belgium: 120
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Worldwide total number of subjects |
120
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EEA total number of subjects |
120
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
63
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From 65 to 84 years |
56
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85 years and over |
1
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Recruitment
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Recruitment details |
This open-label, baseline-controlled study in two groups of subjects: adults aged ≥ 18 and ≤ 60 years and elderly ≥ 61 years was performed in one study center in Belgium between 12 July 2013 and 03 August 2013. | |||||||||||||||
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Pre-assignment
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Screening details |
Subjects underwent screening evaluations to determine eligibility during a period of 14 days preceding Visit 1 at an additional visit (Screening Visit) or on Day 1 (Visit 1). A total of 120 healthy adult and elderly subjects were screened and signed informed consent, and there were no screening failures. | |||||||||||||||
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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 |
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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Adults Aged ≥ 18 and ≤ 60 Years | |||||||||||||||
Arm description |
On Day 1 (Visit 1) subjects aged ≥ 18 and ≤ 60 years received a single dose of Influvac® 0.5 milliliter (mL) by intramuscular (IM) injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Influvac®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One dose of 0.5 mL Influvac® (influenza virus surface antigens (haemagglutinin and neuramidase) of the following strains: A (H1N1), A (H3N2) and B) by IM injection on Day 1 (Visit 1).
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Arm title
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Elderly Aged ≥ 61 Years | |||||||||||||||
Arm description |
On Day 1 (Visit 1) subjects aged ≥ 61 years received a single dose of Influvac® 0.5 mL by IM injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Influvac®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One dose of 0.5 mL Influvac® (influenza virus surface antigens (haemagglutinin and neuramidase) of the following strains: A (H1N1), A (H3N2) and B) by IM injection on Day 1 (Visit 1).
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Baseline characteristics reporting groups
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Reporting group title |
Adults Aged ≥ 18 and ≤ 60 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 18 and ≤ 60 years received a single dose of Influvac® 0.5 milliliter (mL) by intramuscular (IM) injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Elderly Aged ≥ 61 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 61 years received a single dose of Influvac® 0.5 mL by IM injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adults Aged ≥ 18 and ≤ 60 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 18 and ≤ 60 years received a single dose of Influvac® 0.5 milliliter (mL) by intramuscular (IM) injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||
Reporting group title |
Elderly Aged ≥ 61 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 61 years received a single dose of Influvac® 0.5 mL by IM injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||
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End point title |
Percentage of Subjects With Seroprotection for Hemagglutination Inhibition (HI) and Single Radial Hemolysis (SRH) Antibody Titers [1] | ||||||||||||||||||||||||||||||||||||
End point description |
The pre-vaccination (blood sample taken at Day 1) and the post-vaccination (blood sample taken at Day 22) seroprotection rates for each strain are presented. Seroprotection was defined as an HI antibody titer ≥ 40 and a SRH antibody titer ≥ 25 millimeter square (mm^2). The HI assay was performed for all three strains (A (H3N2), A (H1N1), and B strains) and the SRH assay was performed for the B strain only. The CHMP Note for Guidance defined a (the CHMP criteria for immunogenicity) seroprotection rate of > 70% for adults and > 60% for elderly as meeting the requirements for sufficient immunogenicity. The confidence intervals (CI) were calculated based on the Clopper-Pearson method. The efficacy sample set included all vaccinated subjects for whom both the pre- and the post-vaccination HI/SRH antibody titers were available, who did not present an intercurrent respiratory infection (IRI) diagnosed as influenza and who did not present any major protocol deviation.
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End point type |
Primary
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End point timeframe |
Pre-vaccination at Day 1 (Visit 1) and Post-vaccination at Day 22 (Visit 3)
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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: Descriptive statistical analysis was performed for the outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Seroconversion or Significant Increase in HI and SRH Antibody Titers [2] | ||||||||||||||||||||||||
End point description |
The post-vaccination seroconversion or significant increase rates for each strain are presented. For the HI assay, seroconversion was defined as a pre-vaccination HI antibody titer < 10 and a post-vaccination HI antibody titer ≥ 40, and a significant increase was defined as a pre-vaccination HI antibody titer ≥ 10 and a post-vaccination relative increase of ≥ 4-fold. For the SRH assay, seroconversion or a significant increase was defined as a post-vaccination SRH antibody titer ≥ 25 mm^2 and a post-vaccination relative increase of 1.5-fold if the pre-vaccination SRH antibody titer was > 4 mm^2. The HI assay was performed for all three strains (A (H3N2), A (H1N1), and B strains) and the SRH assay was performed for the B strain only. The CHMP Note for Guidance defined a (CHMP criteria for immunogenicity) seroconversion or significant increase in titer of > 40% for adults and > 30% for elderly as meeting the requirements for sufficient immunogenicity. Efficacy sample set were analysed.
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End point type |
Primary
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End point timeframe |
Post-vaccination at Day 22 (Visit 3)
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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: Descriptive statistical analysis was performed for the outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Geometric Mean Fold Increase (MFI) in HI and SRH Antibody Titers [3] | ||||||||||||||||||||||||
End point description |
The post-vaccination (blood sample taken at Day 22) geometric MFI for each strain are presented. Geometric MFI was defined as the geometric mean of the intra-individual increases, that is post-vaccination HI or SRH antibody titer/pre-vaccination HI or SRH antibody titer. The HI assay was performed for all three strains (A (H3N2), A (H1N1), and B strains) and the SRH assay was performed for the B strain only. The CHMP Note for Guidance defined a (the CHMP criteria for immunogenicity) MFI of > 2.5 for adults and > 2.0 for elderly as meeting the requirements for sufficient immunogenicity. The efficacy sample set included all vaccinated subjects for whom both the pre- and the post-vaccination HI/SRH antibody titers were available, who did not present an IRI diagnosed as influenza and who did not present any major protocol deviation.
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End point type |
Primary
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End point timeframe |
Post-vaccination at Day 22 (Visit 3)
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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: Descriptive statistical analysis was performed for the outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Solicited Systemic Reactions | ||||||||||||||||||||||||||||||
End point description |
A subject diary was used to record pre-specified systemic reactions which occurred during the 72 hours after vaccination (solicited reactogenicity). Systemic reactions were assessed for the following categories: fever (≥ 38.0°C), increased sweating, headache, malaise, fatigue, and shivering. These reactions were rated on a four-point scale (none, mild, moderate, severe): none: lack of reactogenicity/inconvenience, mild: presence of mild reactogenicity/inconvenience that did not interfere with normal daily activities, moderate: reactogenicity/inconvenience that had an impact on normal daily activities, and severe: reactogenicity/inconvenience which prevented normal daily activities. Data is presented for the Safety sample set which included all vaccinated subjects for whom both the pre- and the post-vaccination HI/SRH titers were available.
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End point type |
Secondary
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End point timeframe |
Up to 72 hours post-vaccination on Day 1 (Visit 1)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Solicited Local Reactions | |||||||||||||||||||||||||||||||||||||||
End point description |
A subject diary was used to record pre-specified local (vaccination site) reactions occurred which during the 72 hours after vaccination (solicited reactogenicity). Local reactions were assessed for the following categories: redness, swelling, itching, warmth, tenderness (pain or discomfort upon touch), pain, impairment of movement of the arm, induration, and ecchymosis (blue spots). These reactions were rated on a four-point scale (none, mild, moderate, severe): none: lack of reactogenicity/inconvenience, mild: presence of mild reactogenicity/inconvenience that did not interfere with normal daily activities, moderate: reactogenicity/inconvenience that had an impact on normal daily activities, and severe: reactogenicity/inconvenience which prevented normal daily activities. Data is presented for the Safety sample set which included all vaccinated subjects for whom both the pre- and the post-vaccination HI/SRH titers were available.
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End point type |
Secondary
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End point timeframe |
Up to 72 hours post-vaccination on Day 1 (Visit 1)
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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 |
From administration of study vaccination (Day 1) up to Day 22.
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Adverse event reporting additional description |
Safety sample set included the sample of all vaccinated subjects for whom both the pre- and the post-vaccination HI/SRH titers were available.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Adults Aged ≥ 18 and ≤ 60 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 18 and ≤ 60 years received a single dose of Influvac® 0.5 mL by IM injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Elderly Aged ≥ 61 Years
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Reporting group description |
On Day 1 (Visit 1) subjects aged ≥ 61 years received a single dose of Influvac® 0.5 mL by IM injection into the upper arm, after taking a blood sample for baseline antibody titers against each of the vaccine antigens. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
