Clinical Trial Results:
A Phase III, Open-Label, Single-Arm, Multicenter Study to Evaluate the Safety and Immunogenicity of a Trivalent, Surface Antigen Inactivated Subunit Influenza Virus Vaccine (Fluvirin®) in Healthy Adults.
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Summary
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EudraCT number |
2013-000601-23 |
Trial protocol |
DE |
Global end of trial date |
02 Sep 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Dec 2016
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First version publication date |
22 Feb 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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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 |
V78_11S
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01885117 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics S.r.l.
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Sponsor organisation address |
Via Fiorentina 1, Siena, Italy, 53100
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Public contact |
Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.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 |
14 Sep 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 |
02 Sep 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 |
Immunogenicity Objective: To evaluate the antibody response to each influenza vaccine antigen after vaccination with the trivalent, surface antigen inactivated influenza vaccine (TIVf) vaccine, as measured by Single Radial Hemolysis (SRH) or Hemagglutination Inhibition (HI) assay in accordance with Guidance CPMP/BWP/214/96.
Safety Objective: To evaluate the safety of TIVf in adult subjects in compliance with the requirements of the current European Union recommendations for clinical trials related to yearly licensing of influenza vaccines CPMP/BWP/214/96.
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Protection of trial subjects |
Study vaccines were not administered to individuals with known hypersensitivity to any component of the vaccines.
Standard immunization practices were observed and care was taken to administer the injection intramuscularly. As with all injectable vaccines, appropriate medical treatment and supervision was readily available in case of rare anaphylactic reactions following administration of the study vaccine. Epinephrine 1:1000 and diphenhydramine was available in case of any anaphylactic reactions. Care was taken to ensure that the vaccine is not injected into a blood vessel.
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
08 Aug 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 |
Germany: 125
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Worldwide total number of subjects |
125
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EEA total number of subjects |
125
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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) |
75
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From 65 to 84 years |
50
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were enrolled from one center in Germany. | |||||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in study. | |||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
NA
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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TIVf (18 to ≤ 60 Years) | |||||||||
Arm description |
Adult subjects aged 18 to ≤ 60 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived, Fluvirin platform)
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Investigational medicinal product code |
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Other name |
Fluvirin
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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 |
Single 0.5-mL dose of TIVf vaccine is administered IM.
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Arm title
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TIVf (≥ 61Years) | |||||||||
Arm description |
Adult subjects aged ≥ 61 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trivalent influenza virus vaccine (surface antigen, inactivated, egg-derived, Fluvirin platform)
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Investigational medicinal product code |
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Other name |
Fluvirin
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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 |
Single 0.5-mL dose of TIVf vaccine is administered IM.
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Baseline characteristics reporting groups
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Reporting group title |
TIVf (18 to ≤ 60 Years)
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Reporting group description |
Adult subjects aged 18 to ≤ 60 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TIVf (≥ 61Years)
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Reporting group description |
Adult subjects aged ≥ 61 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TIVf (18 to ≤ 60 Years)
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Reporting group description |
Adult subjects aged 18 to ≤ 60 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere. | ||
Reporting group title |
TIVf (≥ 61Years)
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Reporting group description |
Adult subjects aged ≥ 61 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere | ||
Subject analysis set title |
Full Analysis Set (FAS) Immunogenicity
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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 immunogenicity data both before (baseline) and after vaccination.
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Subject analysis set title |
All Enrolled Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All screened subjects who provide informed consent and provide demographic and/or baseline screening assessments and received a subject ID.
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Subject analysis set title |
Per Protocol Set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects in the FAS immunogenicity who were not excluded due to reasons defined prior to unblinding or analysis Examples of subjects excluded due to reasons other than predefined major protocol deviations are:
- Subjects who withdrew informed consent
- Subjects with real-time RT-PCR confirmed influenza during study participation
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End point title |
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf. [1] | ||||||||||||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of subjects in both age groups with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of TIVf.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22 post 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf [2] | |||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase by SRH area against each of the three vaccine strains, three weeks after receiving one dose of TIVf.
Seroconversion is defined as percentage of subjects with a pre vaccination SRH area ≤4mm2 achieving a post vaccination SRH area ≥25 mm2. Significant increase is defined as percentage of subjects with a pre vaccination SRH area >4mm2 achieving at least 50% increase in post vaccination SRH area.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >40% for adults aged 18 to ≤60 years and >30% for subjects aged ≥61 years.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22 post 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Geometric Mean Ratio (GMR) of Post Vaccination Versus Pre Vaccination Geometric Mean Areas(GMAs), After One Dose of TIVf [3] | |||||||||||||||||||||
End point description |
The antibody responses were evaluated in terms of GMRs of post vaccination GMAs to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of TIVf.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 for subjects aged ≥61 years.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22 post 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf. [4] | ||||||||||||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of subjects in both age groups with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of TIVf.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving HI titers ≥ 40 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22 post vaccination
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| Notes [4] - 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIVf. [5] | |||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase in HI antibody titers after receiving one dose of TIVf.
The related European (CHMP) criterion for the assessment of immunogenicity is met if>40 % for adults aged 18 to ≤60 years and>30% for subjects aged ≥61 years achieve seroconversion or significant increase in post vaccination HI titers.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22 post vaccination
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| Notes [5] - 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf [6] | |||||||||||||||||||||
End point description |
The antibody responses following one dose of TIVf were evaluated in terms of GMRs of post vaccination against pre vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of TIVf.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 for subjects aged ≥61 years.
Analysis was done on the per-protocol population.
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End point type |
Primary
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End point timeframe |
Day 22/Day 1
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| Notes [6] - 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Subjects Reporting Solicited Adverse Events (AEs) After Receiving One Dose of TIVf. [7] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of adult and elderly subjects reporting solicited local and systemic AEs and other solicited AEs after receiving one dose of TIVf are reported.
Analysis was done on the safety set population.
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End point type |
Primary
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End point timeframe |
Day 1 through Day 4 post vaccination
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| Notes [7] - 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: No statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVf. [8] | |||||||||||||||||||||||||||
End point description |
The number of subjects in both age groups reporting any unsolicited AEs (between Day 1 to 4), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (throughout the study period), after receiving one dose of TIVf is reported.
Analysis was done on the safety analysis set.
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End point type |
Primary
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End point timeframe |
Day 1 through Day 22 post vaccination
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| Notes [8] - 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: No statistical analysis was performed. |
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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 |
All solicited AEs and unsolicited AEs were collected from Day1 to Day 4; all unsolicited SAEs, medically attended AEs, AEs leading to withdrawal from the study were collected from Day1 to Day 22.
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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 |
16
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Reporting groups
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Reporting group title |
TIVf (18 to ≤ 60 Years)
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Reporting group description |
Adult subjects aged 18 to ≤ 60 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TIVf (≥ 61Years)
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Reporting group description |
Adult subjects aged ≥ 61 years received one dose of trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVf), formulation 2013/2014 Northern Hemisphere | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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. | |||
| Not specified | |||
