Clinical Trial Results:
A Phase II, Open-Label, Single-Arm, Multicenter Study to Evaluate the Safety and Immunogenicity of a Trivalent, Surface Antigen Inactivated Subunit Influenza Virus Vaccine Including MF59C.1 Adjuvant (Fluad®)in Healthy Adults ≥65 Years of Age.
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Summary
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EudraCT number |
2013-000607-16 |
Trial protocol |
BE |
Global end of trial date |
20 Aug 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 |
21 Nov 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 |
V70_44S
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01879540 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines
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Sponsor organisation address |
Via Fiorentina, Siena, Italy, 53100
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Public contact |
Michelangelo Barone, Novartis Vaccines and Diagnostics S.r.l., 0039 0577243516, michelangelo.barone@novartis.com
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Scientific contact |
Michelangelo Barone, Novartis Vaccines and Diagnostics S.r.l., 0039 0577243516, michelangelo.barone@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 |
04 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 |
20 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 |
Immunogenicity Objective
To evaluate the antibody response to each influenza vaccine antigen after vaccination with the trivalent, surface antigen inactivated subunit influenza virus vaccine including MF59C.1 (aTIV) 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 aTIV in adult subjects ≥65 years of age.
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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 |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 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: 63
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Worldwide total number of subjects |
63
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EEA total number of subjects |
63
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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) |
0
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From 65 to 84 years |
63
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled from one study center in Belgium. | ||||||
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Pre-assignment
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Screening details |
All the subject from Belgium 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 |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
No blinding was performed.
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Arms
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Arm title
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aTIV | ||||||
Arm description |
Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Trivalent, Surface Antigen Inactivated Subunit Influenza Virus Vaccine Including MF59C.1 Adjuvant
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Investigational medicinal product code |
NA
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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 of aTIV vaccine administered is administered IM.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
aTIV
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Reporting group description |
Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), formulation 2013/2014 Northern Hemisphere. | ||
Subject analysis set title |
aTIV-PPS
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects who have received study vaccination and provided immunogenicity data both at baseline and after vaccination; did not withdraw informed consent and did not have RT-PCR confirmed influenza during the study.
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Subject analysis set title |
aTIV- Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who have post-vaccination AE or reactogenicity records.
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End point title |
Percentages of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV [1] | ||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of aTIV.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >60%.
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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: 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 SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV [2] | ||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age achieving seroconversion or significant increase in SRH area against each of the three vaccine strains, three weeks after receiving one dose of aTIV.
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>30% of subjects achieve seroconversion or significant increase in post-vaccination SRH area.
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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: Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine |
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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 Area, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV [3] | ||||||||||||||
End point description |
The antibody responses following one dose of aTIV were evaluated in terms of geometric mean ratio of post vaccination to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of aTIV.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is > 2.0.
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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: Safety objectives were analysed descriptively. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentages of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV. [4] | ||||||||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of aTIV.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the of subjects achieving HI titers ≥ 40 is >60%.
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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: 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, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV [5] | ||||||||||||||
End point description |
Immunogenicity was assessed in terms of percentages of adult subjects ≥65 years of age achieving seroconversion or significant increase in HI antibody titers after receiving one dose of aTIV.
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 >30% of subjects achieve seroconversion or significant increase in post-vaccination HI titers.
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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 |
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination HI Titers, Against Each of Three Vaccine Strains After Receiving One Dose of aTIV [6] | ||||||||||||||
End point description |
The antibody responses following one dose of aTIV were evaluated in terms of GMRs of post vaccination to pre vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of aTIV.
The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is > 2.0.
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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: Safety objectives were analysed descriptively. |
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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 aTIV. [7] | ||||||||||||||||||||||||||||||||||||||
End point description |
The number of adult subjects ≥65 years of age reporting solicited local and systemic
adverse events and other solicited adverse events after receiving one dose of aTIV are
reported.
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End point type |
Primary
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End point timeframe |
Day 1 to 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: 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 Unsolicited Adverse Events After Receiving One dose of aTIV. [8] | ||||||||||||||||||||
End point description |
The number of adult subjects ≥65 years of age subjects reporting any unsolicited adverse event (AEs) between Day 1 to 4 and serious adverse events (SAEs), medically attended AEs, AEs leading to withdrawal from the study between Day 1 to Day 22 after receiving one dose of aTIV are reported.
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End point type |
Primary
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End point timeframe |
Day 1 to 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: Safety objectives were analysed descriptively. |
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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 |
Throughout the study. ( solicitated and unsolicited from Day 1 to Day 4)
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Adverse event reporting additional description |
Any solicited and unsolicited adverse events were reported from day 1 to day 4. Unsolicited SAE, medically attended AEs, AEs leading to withdrawal from the study, and concomitant medications/vaccinations associated with these events were collected from day 1 through 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 |
aTIV
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Reporting group description |
Adult subjects ≥65 years of age received one dose of a trivalent, surface antigen, inactivated influenza vaccine including MF59C.1 adjuvant (aTIV), 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 | |||
