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 Produced in Mammalian Cell Culture (Optaflu®) in Healthy Adults.
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Summary
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EudraCT number |
2013-000621-30 |
Trial protocol |
DE |
Global end of trial date |
08 Sep 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
29 Jul 2016
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First version publication date |
22 Oct 2014
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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 |
V58_33S
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01880697 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics
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Sponsor organisation address |
Via Fiorentina 1, Siena, Italy,
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Public contact |
Head of Central and Northern Europe, Novartis Vaccines and Diagnostics GmbH, +49 080246465401, dietrich.bosse@novartis.com
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Scientific contact |
Head of Central and Northern Europe, Novartis Vaccines and Diagnostics GmbH, +49 080246465401, dietrich.bosse@novartis.com
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Sponsor organisation name |
Novartis Vaccines and Diagnostics
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Sponsor organisation address |
Via Fiorentina 1, Siena, Italy,
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Public contact |
Novartis Vaccines , Posting Director, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Novartis Vaccines , Posting Director, 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 |
20 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 |
08 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 TIVc 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 TIVc 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 |
This clinical study was designed, implemented and reported in accordance with the ICH Harmonized Tripartite Guidelines for GCP, with applicable local regulations, including the European Directive 2001/20/EC, the US CFR Title 21, and the Japanese Ministry of Health, Labor, and Welfare, Novartis codes on the protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 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: 126
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Worldwide total number of subjects |
126
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EEA total number of subjects |
126
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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) |
82
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From 65 to 84 years |
44
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were enrolled from 1 study centre in Germany | |||||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in the 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 | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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TIVc (≥18 to ≤ 60 Years) | |||||||||
Arm description |
Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trivalent influenza virus vaccine (surface antigen, inactivated, cell-based)
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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 |
Single 0.5-mL dose intramuscularly on day 1
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Arm title
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TIVc (≥ 61 Years) | |||||||||
Arm description |
Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Trivalent influenza virus vaccine (surface antigen, inactivated, cell-based)
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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 |
Single 0.5-mL dose intramuscularly on day 1
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Baseline characteristics reporting groups
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Reporting group title |
TIVc (≥18 to ≤ 60 Years)
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Reporting group description |
Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TIVc (≥ 61 Years)
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Reporting group description |
Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Enrolled Set
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All screened subjects who provided informed consent, provided 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 who had received study vaccination and provided immunogenicity data both at baseline and after vaccination, and were not excluded due to reasons defined prior to unblinding or analysis, e.g. did not withdraw informed consent and did not have RT-PCR confirmed influenza during the study.
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Subject analysis set title |
Safety Set (solicited AEs and other solicited events)
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects in the Exposed Set who provided post-vaccination reactogenicity data
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Subject analysis set title |
Safety Set (unsolicited AEs)
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects in the Exposed Set who had post-vaccination unsolicited AE records
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End points reporting groups
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Reporting group title |
TIVc (≥18 to ≤ 60 Years)
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Reporting group description |
Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | ||
Reporting group title |
TIVc (≥ 61 Years)
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Reporting group description |
Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | ||
Subject analysis set title |
Enrolled Set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All screened subjects who provided informed consent, provided 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 who had received study vaccination and provided immunogenicity data both at baseline and after vaccination, and were not excluded due to reasons defined prior to unblinding or analysis, e.g. did not withdraw informed consent and did not have RT-PCR confirmed influenza during the study.
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Subject analysis set title |
Safety Set (solicited AEs and other solicited events)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the Exposed Set who provided post-vaccination reactogenicity data
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Subject analysis set title |
Safety Set (unsolicited AEs)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the Exposed Set who had post-vaccination unsolicited AE records
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End point title |
Number of subjects reporting unsolicited adverse events after receiving one dose of TIVc. [1] | ||||||||||||||||||||||||||||||
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 TIVc is reported. The analysis was performed on the Solicited Safety 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 [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: All safety analyses were run in the safety population. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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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 TIVc [2] | ||||||||||||||||||||||||||||||
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 TIVc. 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. The analysis was performed on the Per Protocol Set.
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects achieving seroconversion or significant increase by SRH area, against each of three vaccine strains after receiving one dose of TIVc [3] | |||||||||||||||||||||
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 TIVc. 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. The analysis was performed on the Per Protocol Set.
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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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), against each of three vaccine strains after receiving one dose of TIVc [4] | |||||||||||||||||||||
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 TIVc. 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 in for subjects aged ≥61 years. The analysis was performed on the Per Protocol Set.
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End point type |
Primary
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End point timeframe |
Day 22/Day 1
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of subjects with hemagglutination inhibition (HI) titer ≥ 1:40, against each of three vaccine strains after receiving one dose of TIVc [5] | ||||||||||||||||||||||||||||||
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 TIVc. 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. The analysis was performed on the Per Protocol Set.
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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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 TIVc [6] | |||||||||||||||||||||
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 TIVc. Seroconversion is defined as percentage of subjects with a pre-vaccination HI titer <10 to a post-vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre-vaccination HI titer >10 to at least a 4-fold increase in post-vaccination HI antibody titers.
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.
The analysis was performed on the Per Protocol Set.
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End point type |
Primary
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End point timeframe |
Day 22 post-vaccination
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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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 HI antibody titers, against each of three vaccine strains after receiving one dose of TIVc [7] | |||||||||||||||||||||
End point description |
The antibody responses following one dose of TIVc 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 TIVc. 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. The analysis was performed on the Per Protocol Set.
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End point type |
Primary
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End point timeframe |
Day 22/Day1
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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: There was no statistical null hypothesis associated with the immunogenicity objective. |
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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 after receiving one dose of TIVc. [8] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of adult and elderly subjects reporting solicited local and systemic adverse events and other solicited adverse events after receiving one dose of TIVc.
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End point type |
Primary
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End point timeframe |
Day 1 to Day 4 post-vaccination. Analysis was done on the solicited safety set population.
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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: All safety analyses were run in the safety population. |
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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 Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal were collected from Day 1 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 |
16.0
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Reporting groups
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Reporting group title |
TIVc (≥18 to ≤ 60 Years)
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Reporting group description |
Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TIVc (≥ 61 Years)
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Reporting group description |
Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) 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. | |||
| None reported | |||
