Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 4 for:    flu-v | influenza

A Randomised, Double-blind, Placebo-controlled Phase IIb Trial to Test FLU-v Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02962908
Recruitment Status : Completed
First Posted : November 15, 2016
Results First Posted : April 8, 2019
Last Update Posted : September 16, 2020
Sponsor:
Collaborators:
Seventh Framework Programme
University of Groningen
University Medical Center Groningen
Robert Koch Institut
Norwegian Institute of Public Health
Information provided by (Responsible Party):
PepTcell Limited

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Influenza
Interventions Biological: FLU-v
Biological: adjuvanted FLU-v
Biological: Saline
Biological: Adjuvanted placebo
Enrollment 175
Recruitment Details  
Pre-assignment Details

195 subjects were screened. Of those, N=20 subjects were removed from the study prior randomisation due to:

  • lost to follow up n=3
  • didn't wish to continue after screening visit n=9
  • did not meet inclusion/exclusion criteria n=8
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Period Title: Overall Study
Started 58 58 32 27
Completed 58 50 32 24
Not Completed 0 8 0 3
Reason Not Completed
Lost to Follow-up             0             3             0             1
Withdrawal by Subject             0             3             0             2
Protocol Violation             0             1             0             0
Physician Decision             0             1             0             0
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo Total
Hide Arm/Group Description

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Total of all reporting groups
Overall Number of Baseline Participants 58 57 32 27 174
Hide Baseline Analysis Population Description
A subject in 1x FLU-v adjuvanted group received 1x non-adjuvanted FLU-v. Subject completed the study but with this treatment, the subject could not be assigned to any group for analysis. This is the reason why 58 subjects were randomised to this group but only 57 were analysed, making the total subject number 174 rather than 175.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 57 participants 32 participants 27 participants 174 participants
40.02  (13.691) 40.12  (12.221) 41.19  (12.458) 39.07  (13.074) 40.12  (12.806)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 57 participants 32 participants 27 participants 174 participants
Female
36
  62.1%
30
  52.6%
18
  56.3%
13
  48.1%
97
  55.7%
Male
22
  37.9%
27
  47.4%
14
  43.8%
14
  51.9%
77
  44.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 57 participants 32 participants 27 participants 174 participants
Asian
1
   1.7%
1
   1.8%
0
   0.0%
0
   0.0%
2
   1.1%
Black of African descendant
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
56
  96.6%
54
  94.7%
32
 100.0%
27
 100.0%
169
  97.1%
Other
1
   1.7%
2
   3.5%
0
   0.0%
0
   0.0%
3
   1.7%
Unknown or not reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
previous influenza vaccination   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 57 participants 32 participants 27 participants 174 participants
Never received influenza vaccination
37
  63.8%
29
  50.9%
15
  46.9%
18
  66.7%
99
  56.9%
Received in the previous 2 years
14
  24.1%
20
  35.1%
12
  37.5%
5
  18.5%
51
  29.3%
Received over 2 years ago
7
  12.1%
8
  14.0%
5
  15.6%
4
  14.8%
24
  13.8%
[1]
Measure Description: Subjects were asked whether they had received previous influenza vaccinations and whether it was within 2 years or more from joining the trial.
[2]
Measure Analysis Population Description: This baseline measure was only analysed in the FAS population, that is the Full Analysis Set which includes all those subjects that completed vaccination and had at least pre-vaccination immunogenicity data and at least one post-vaccination time point.
HAI titer at screening   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 57 participants 32 participants 27 participants 174 participants
HAI≥80 B/Phuket/3073/2013
21
  36.2%
16
  28.1%
12
  37.5%
7
  25.9%
56
  32.2%
HAI≥80 B/Brisbane/60/2008
18
  31.0%
19
  33.3%
12
  37.5%
7
  25.9%
56
  32.2%
HAI≥40 A/Hong Kong/5738/2014 (H3N2)
25
  43.1%
26
  45.6%
18
  56.3%
10
  37.0%
79
  45.4%
HAI≥40 A/Michigan/45/15 (H1N1)
23
  39.7%
29
  50.9%
16
  50.0%
11
  40.7%
79
  45.4%
any of the above
39
  67.2%
40
  70.2%
26
  81.3%
17
  63.0%
122
  70.1%
[1]
Measure Description: Serum samples were collected at screening (summer-autumn 2016) and later analysed for pre-existing neutralising antibodies against the main influenza strains that circulated in the Netherlands during the influenza season of 2016-2017 (B/Phuket/3073/2013, B/Brisbane/60/2008, A/Hong Kong/5738/2014 (H3N2) and A/Michigan/45/15 (H1N1)). The number of subjects with a HA titer for A strains ≥ 40 and with HA ≥ 80 for B strains was recorded in each group.
1.Primary Outcome
Title CD4+ and CD8+ Th1 Cellular Immunogenicity on Day 42
Hide Description Comparison of the TH1 response in the treatment arms compared to placebo from baseline to day 42 following vaccination, calculated as the median fold change in the number of CD4+ and CD8+ T cells positive for IFN-gamma, TNF-alpha, IL-2 and CD107a. Fold change is calculated as the number of cells on day 42 divided by number of cells on day 0.
Time Frame day 0 to day 42
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population: Full Analysis Set corresponds to subjects that completed the vaccination successfully and provided samples for immunogenicity analysis for baseline (pre-vaccination) and at least one time point post-vaccination. Only samples with acceptable positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Median (95% Confidence Interval)
Unit of Measure: fold change
IFN-gamma CD4+
0.5
(-0.2 to 1.1)
5.9
(1.0 to 10.9)
1.0
(-0.7 to 2.6)
0.2
(-0.6 to 1.0)
TNF-alpha CD4+
0.0
(-0.1 to 0.1)
5.0
(-10.9 to 20.9)
0.0
(-0.5 to 0.5)
0.0
(-0.3 to 0.3)
IL-2 CD4+
0.0
(-1.1 to 1.1)
8.2
(-0.4 to 16.7)
0.0
(-0.4 to 0.4)
0.0
(-0.1 to 0.1)
CD107a CD4+
0.0
(-0.4 to 0.4)
2.0
(0.3 to 3.7)
0.0
(-0.5 to 0.5)
0.0
(-0.2 to 0.2)
IFN-gamma CD8+
0.3
(-0.1 to 0.6)
0.3
(-0.2 to 0.7)
0.0
(-0.1 to 0.1)
0.0
(-0.3 to 0.3)
TNF-alpha CD8+
0.3
(0.0 to 0.6)
0.3
(-0.6 to 1.3)
0.0
(-0.6 to 0.6)
0.0
(-0.1 to 0.1)
IL-2 CD8+
0.5
(0.1 to 0.9)
0.0
(-0.4 to 0.4)
0.0
(-0.5 to 0.5)
0.0
(-0.7 to 0.7)
CD107a CD8+
0.0
(-0.2 to 0.2)
0.0
(-0.5 to 0.5)
0.0
(-0.2 to 0.2)
0.0
(-0.1 to 0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IFN-gamma from day 0 and to 42.
Type of Statistical Test Other
Comments Inequality test.
Statistical Test of Hypothesis P-Value 0.45
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IFN-gamma from day 0 and to 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for TNF-alpha from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for TNF-alpha from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IL-2 from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IL-2 from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for CD107a from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for CD107a from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IFN-gamma from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IFN-gamma from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.38
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for TNF-alpha from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.49
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for TNF-alpha from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.156
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IL-2 from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for CD107a from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for CD107a from day 0 to day 42.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title CD4+ and CD8+ Th1 Cellular Immunogenicity on Day 180
Hide Description Comparison of the TH1 response in the treatment arms compared to placebo from baseline to day 180 following vaccination, calculated as the median fold change in the number of CD4+ and CD8+ T cells positive for IFN-gamma, TNF-alpha, IL-2 and CD107a. Fold change is calculated as the number of cells on day 180 divided by number of cells on day 0.
Time Frame Day 0 to day 180
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population: Full Analysis Set corresponds to subjects that completed the vaccination successfully and provided samples for immunogenicity analysis for baseline (pre-vaccination) and at least one time point post-vaccination. Only samples with acceptable positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Median (95% Confidence Interval)
Unit of Measure: fold change
IFN-gamma CD4+
0.5
(0.2 to 1.2)
4.4
(1.0 to 7.8)
0.1
(-0.4 to 0.6)
0.9
(-1.4 to 3.2)
TNF-alpha CD4+
0.0
(0.0 to 0.0)
0.6
(-3.5 to 4.8)
0.0
(0.0 to 0.0)
0.0
(-1.2 to 1.2)
IL-2 CD4+
0.2
(-0.6 to 1.1)
6.5
(2.1 to 10.9)
0.0
(-0.2 to 0.2)
0.0
(-0.1 to 0.1)
CD107a CD4+
0.6
(-0.1 to 1.3)
1.0
(0.2 to 1.8)
0.0
(-0.1 to 0.1)
0.6
(-0.7 to 1.9)
IFN-gamma CD8+
0.0
(-0.5 to 0.6)
0.2
(-0.4 to 0.7)
0.0
(-0.6 to 0.6)
0.0
(-0.5 to 0.5)
TNF-alpha CD8+
0.1
(-0.5 to 0.6)
0.2
(-0.2 to 0.6)
0.1
(-0.7 to 0.9)
0.1
(-1.8 to 1.85)
IL-2 CD8+
0.3
(-0.3 to 0.7)
0.0
(-0.6 to 0.6)
0.0
(-0.3 to 0.3)
0.0
(-0.4 to 0.4)
CD107a CD8+
0.0
(-0.4 to 0.4)
0.0
(-0.9 to 1.5)
0.0
(-0.5 to 0.5)
0.5
(-3.2 to 6.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IFN-gamma from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IFN-gamma from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for TNF-alpha from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.87
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for TNF-alpha from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IL-2 from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.076
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for IL-2 from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for CD107a from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD4+ T cells positive for CD107a from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IFN-gamma from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IFN-gamma from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for TNF-alpha from day 0 to day 180.
Type of Statistical Test Other
Comments inequality
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for TNF-alpha from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IL2 from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for IL2 from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for CD107a from day 0 to day 180.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the difference in median fold increase in number of CD8+ T cells positive for CD107a from day 0 to day 180.
Type of Statistical Test Other
Comments inequality
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Primary Outcome
Title Percentage of TH1 Cytokine Responders (Responders Defined as Those With >2 Fold Median Increase From Baseline in CD4+ and CD8+ T-cells Positive for Particular Cytokine)
Hide Description To compare the number of subjects that showed at least a two-fold increase on day 42 and day 180 following vaccination in the number of CD4+and CD8+ T-cells secreting TH1 cytokines in all groups.
Time Frame prevaccination, day 42 (21 days after last vaccination) and day 180.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population: Full Analysis Set corresponds to subjects that completed the vaccination successfully and provided samples for immunogenicity analysis for baseline (pre-vaccination) and at least one time point post-vaccination. Only samples with acceptable positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Measure Type: Count of Participants
Unit of Measure: Participants
IFNg+CD4+ day 42 Number Analyzed 51 participants 44 participants 27 participants 19 participants
23
  45.1%
40
  90.9%
13
  48.1%
8
  42.1%
TNFalpha+ CD4+ day 42 Number Analyzed 52 participants 44 participants 27 participants 18 participants
16
  30.8%
33
  75.0%
12
  44.4%
9
  50.0%
IL2+ CD4+ day 42 Number Analyzed 52 participants 44 participants 27 participants 19 participants
23
  44.2%
36
  81.8%
13
  48.1%
4
  21.1%
CD107a+ CD4+ day 42 Number Analyzed 47 participants 38 participants 23 participants 14 participants
22
  46.8%
26
  68.4%
8
  34.8%
4
  28.6%
IFNg+ CD4+ day 180 Number Analyzed 53 participants 44 participants 27 participants 19 participants
26
  49.1%
37
  84.1%
8
  29.6%
11
  57.9%
TNFa+ CD4+ day 180 Number Analyzed 53 participants 44 participants 27 participants 19 participants
17
  32.1%
26
  59.1%
9
  33.3%
9
  47.4%
IL-2+ CD4+ day 180 Number Analyzed 53 participants 44 participants 27 participants 19 participants
26
  49.1%
39
  88.6%
13
  48.1%
9
  47.4%
CD107a+ CD4+ day 180 Number Analyzed 50 participants 37 participants 22 participants 14 participants
24
  48.0%
21
  56.8%
5
  22.7%
8
  57.1%
IFN-gamma day 42 CD8+ Number Analyzed 53 participants 44 participants 27 participants 18 participants
22
  41.5%
16
  36.4%
9
  33.3%
4
  22.2%
TNF-alpha day 42 CD8+ Number Analyzed 53 participants 44 participants 27 participants 18 participants
22
  41.5%
23
  52.3%
10
  37.0%
6
  33.3%
IL2 day 42 CD8+ Number Analyzed 52 participants 44 participants 27 participants 19 participants
25
  48.1%
17
  38.6%
9
  33.3%
8
  42.1%
CD107a day 42 CD8+ Number Analyzed 47 participants 44 participants 27 participants 18 participants
23
  48.9%
19
  43.2%
5
  18.5%
2
  11.1%
IFN-gamma day 180 CD8+ Number Analyzed 53 participants 44 participants 27 participants 19 participants
27
  50.9%
22
  50.0%
13
  48.1%
7
  36.8%
TNF-alpha day 180 CD8+ Number Analyzed 53 participants 44 participants 27 participants 19 participants
21
  39.6%
18
  40.9%
14
  51.9%
12
  63.2%
IL2 day 180 CD8+ Number Analyzed 53 participants 44 participants 27 participants 19 participants
11
  20.8%
16
  36.4%
8
  29.6%
5
  26.3%
CD107a day 180 CD8+ Number Analyzed 53 participants 44 participants 27 participants 19 participants
19
  35.8%
24
  54.5%
8
  29.6%
8
  42.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ IFNgamma responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ IFNgamma responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ TNF alpha responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ TNF alpha responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ IL-2 responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ IL-2 responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ CD107a responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ CD107a responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ IFNgamma responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.096
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ IFNgamma responders on day 180.Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.049
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ TNF alpha responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.91
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ TNF alpha responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ IL-2 responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ IL-2 responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD4+ CD107a responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.044
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD4+ CD107a responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ IFN-gamma responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ IFN-gamma responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ TNF-alpha responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ TNF-alpha responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.175
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ IL2 responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ IL2 responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ CD107a responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ CD107a responders on day 42. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ IFN-gamma responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.81
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ IFN-gamma responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.34
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ TNF-alpha responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ TNF-alpha responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.105
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ IL2 responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.38
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ IL2 responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of CD8+ CD107a responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of CD8+ CD107a responders on day 180. Differences considered significant if p-value <0.05.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method Chi squared or Fisher's exact test
Comments [Not Specified]
4.Primary Outcome
Title Percentage of CD4+ and CD8+ TH1 Cytokine Responders Determined by Mixture Models for Single-cell Assays (MIMOSA)
Hide Description To compare the number of subjects identified as responders for cytokine markers as determined by MIMOSA analysis (Responders based on a false discovery rate derived P-value <0.05).
Time Frame day 0 to day 42 and day 180
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set corresponds to subjects that completed the vaccination successfully and provided samples for immunogenicity analysis for baseline (pre-vaccination) and at least one time point post-vaccination. Only samples with acceptable positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Measure Type: Count of Participants
Unit of Measure: Participants
IFN-gamma day 42 CD4+ Number Analyzed 54 participants 50 participants 30 participants 23 participants
7
  13.0%
38
  76.0%
1
   3.3%
2
   8.7%
TNF-alpha day 42 CD4+ Number Analyzed 55 participants 50 participants 30 participants 22 participants
3
   5.5%
22
  44.0%
1
   3.3%
0
   0.0%
IL-2 day 42 CD4+ Number Analyzed 55 participants 50 participants 30 participants 23 participants
1
   1.8%
28
  56.0%
1
   3.3%
0
   0.0%
CD107a day 42 CD4+ Number Analyzed 51 participants 48 participants 29 participants 21 participants
1
   2.0%
5
  10.4%
1
   3.4%
0
   0.0%
IFN-gamma day 180 CD4+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
8
  14.3%
31
  63.3%
2
   6.7%
1
   4.8%
TNF-alpha day 180 CD4+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
2
   3.6%
12
  24.5%
1
   3.3%
0
   0.0%
IL-2 day 180 CD4+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
1
   1.8%
28
  57.1%
1
   3.3%
0
   0.0%
CD107a day 180 CD4+ Number Analyzed 53 participants 44 participants 25 participants 19 participants
2
   3.8%
4
   9.1%
2
   8.0%
1
   5.3%
IFN-gamma day 42 CD8+ Number Analyzed 56 participants 50 participants 30 participants 22 participants
3
   5.4%
3
   6.0%
0
   0.0%
0
   0.0%
TNF-alpha day 42 CD8+ Number Analyzed 56 participants 50 participants 30 participants 22 participants
0
   0.0%
1
   2.0%
0
   0.0%
0
   0.0%
IL2 day 42 CD8+ Number Analyzed 56 participants 50 participants 30 participants 23 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
CD107a day 42 CD8+ Number Analyzed 55 participants 50 participants 30 participants 22 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
IFN-gamma day 180 CD8+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
4
   7.1%
3
   6.1%
0
   0.0%
1
   4.8%
TNF-alpha day 180 CD8+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
1
   1.8%
1
   2.0%
0
   0.0%
0
   0.0%
IL2 day 180 CD8+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
CD107a day 180 CD8+ Number Analyzed 56 participants 49 participants 30 participants 21 participants
0
   0.0%
1
   2.0%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IFN-gamma at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing TNF-alpha at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IL-2 at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing CD107a at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IFN-gamma at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing TNF-alpha at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IL2 at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing CD107a at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IFN-gamma at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.48
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing TNF-alpha at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IL2 at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing CD107a at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IFN-gamma at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing TNF-alpha at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing IL2 at day 180
Type of Statistical Test Other
Comments inequality
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD4+ T-cell producing CD107a at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing IFN-gamma at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing IFN-gamma at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.55
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing TNF-alpha at day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing IFN-gamma at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.29
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing TNF-alpha at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing IFN-gamma at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing TNF-alpha at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of responders determined by MIMOSA analysis of CD8+ T-cell producing CD107a at day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Primary Outcome
Title IFN-gamma Responses Measured by ELISA
Hide Description Median fold change in IFN-gamma secretion from PBMCs stimulated in vitro with FLU-v antigens. IFN-gamma secretion was measured by ELISA.Fold change was measured as secretion on day 42 divided by secretion on day 0, and secretion on day 180 divided by secretion on day 0.
Time Frame day 0 to day 42, day 0 to day 180
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set corresponds to subjects that completed the vaccination successfully and provided samples for immunogenicity analysis for baseline (pre-vaccination) and at least one time point post-vaccination. Only samples with acceptable positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Median (95% Confidence Interval)
Unit of Measure: fold change
Day 42 Number Analyzed 47 participants 43 participants 25 participants 20 participants
0.8
(-2.3 to 3.9)
59.0
(33.3 to 84.7)
1.0
(-0.8 to 2.8)
1.0
(-2.4 to 4.4)
Day 180 Number Analyzed 48 participants 43 participants 23 participants 20 participants
1.0
(0.7 to 1.3)
27.3
(5.2 to 49.4)
1.0
(-1.4 to 3.4)
0.9
(-0.0 to 1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of median fold-increase in IFN-gamma secretion as measured by ELISA on day 42. p<0.05 considered statistically significant.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of median fold-increase in IFN-gamma secretion as measured by ELISA on day 42. p<0.05 considered statistically significant.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of median fold-increase in IFN-gamma secretion as measured by ELISA on day 180. p<0.05 considered statistically significant.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of median fold-increase in IFN-gamma secretion as measured by ELISA on day 180. p<0.05 considered statistically significant.
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Primary Outcome
Title Percentage of Responders on Day 42 and Day 180 for IFNgamma Secretion by PBMCs
Hide Description Responders were defined as subjects having at least a two-fold increase in the amount of IFNg secreted on day 42 and day 180 compared the amount secreted on day 0. IFNg was measured by ELISA
Time Frame prevaccination (day 0) to postvaccination (day 42 and day 180)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set including subjects that completed vaccination and provided immunogenicity samples for prevaccination and at least one post-vaccination time point (day 42 or day 180). Only samples that meet the acceptance criteria based on the positive and negative controls were used in the analysis.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Measure Type: Count of Participants
Unit of Measure: Participants
day 42 Number Analyzed 47 participants 44 participants 25 participants 20 participants
28
  59.6%
42
  95.5%
10
  40.0%
9
  45.0%
day 180 Number Analyzed 48 participants 43 participants 23 participants 20 participants
22
  45.8%
40
  93.0%
13
  56.5%
11
  55.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of number of responders on day 42. A subject was considered a "responder" if an increase of secreted IFNgamma of at least two fold was observed from day 0 to day 42.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of number of responders on day 42. A subject was considered a "responder" if an increase of secreted IFNgamma of at least two fold was observed from day 0 to day 42.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of number of responders on day 180. A subject was considered a "responder" if an increase of secreted IFNgamma of at least two fold was observed from day 0 to day 180.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.399
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of number of responders on day 180. A subject was considered a "responder" if an increase of secreted IFNgamma of at least two fold was observed from day 0 to day 180.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Primary Outcome
Title Solicited AEs
Hide Description To evaluate the solicited AEs in all subjects
Time Frame until 21 days after the last dosing of the study vaccine
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: All subjects that received at least one vaccination
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 57 32 27
Measure Type: Number
Unit of Measure: Events
All solicited AEs 275 485 149 147
Solicited AEs unrelated to vaccination 12 13 8 0
Solicited AEs unlikely related to vaccination 72 74 71 34
Solicited AEs possibly related to vaccination 108 134 64 39
Solicited AEs probably related to vaccination 16 16 0 12
Solicited AEs definately related to vaccination 67 248 6 62
Mild solicited AEs 210 339 124 111
Moderate solicited AEs 59 132 24 34
Severe solicited AEs 6 14 1 2
8.Secondary Outcome
Title Antibody Responses to FLU-v
Hide Description To evaluate the IgG levels as a measure of antibody responses to FLU-v on day 0 (baseline) and on days 42 and 180 following FLU-v vaccination. IgG antibodies were measured by ELISA. The geometric mean for each treatment group was provided.
Time Frame prevaccination, day 42 (21 days after last vaccination) and day 180.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set includes all subjects that completed the vaccination successfully and provided samples for immunogenicity analysis at baseline (Pre-vaccination) and at least one time point post-vaccination.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Geometric Mean (Standard Error)
Unit of Measure: IgG ng/ml
day 0 499.11  (103.19) 362.86  (82.93) 331.16  (59.00) 371.89  (67.47)
day 42 2593.02  (1652.34) 8740.48  (2432.90) 336.37  (58.92) 381.17  (61.18)
day 180 1276.34  (344.52) 4769.16  (1131.67) 344.88  (66.57) 387.26  (61.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of geometric mean IgG titers specific to FLU-v antigens on day 42 post-vaccination.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of geometric mean IgG titers specific to FLU-v antigens on day 42.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of geometric mean IgG titers specific to FLU-v antigens on day 180.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of geometric mean IgG titers specific to FLU-v antigens on day 180.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Th2 Cytokine Responses (IL-4)
Hide Description To evaluate the level of TH2 cytokines (IL-4) from baseline in all groups 42 and 180 days following FLU-v vaccination.
Time Frame prevaccination, day 42 (21 days after last vaccination) and day 180.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set includes all subjects that completed the vaccination successfully and provided samples for immunogenicity analysis at baseline (Pre-vaccination) and at least one time point post-vaccination. Only samples that met the acceptance criteria based on positive and negative controls were used in the analysis
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Measure Type: Number
Unit of Measure: percentage of responders
IL-4+CD4+ cells day 42 NA [1]  NA [1]  NA [1]  NA [1] 
IL-4+ CD8+ cells day 42 NA [1]  NA [1]  NA [1]  NA [1] 
IL-4+ CD4+ cells day 180 NA [1]  NA [1]  NA [1]  NA [1] 
IL-4+ CD8+ cells day 180 NA [1]  NA [1]  NA [1]  NA [1] 
[1]
Below level of detection
10.Other Pre-specified Outcome
Title Unsolicited AEs and SAEs
Hide Description To evaluate unsolicited AEs and SAEs in all subjects
Time Frame From the start of the vacciantion until study completion for each subject, approximately no more than 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all subjects that received at least one vaccination
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 57 32 27
Measure Type: Number
Unit of Measure: events
All unsolicited AEs 19 24 13 9
Unsolicited AEs unrelated to the vaccine 8 11 5 5
Unsolicited AEs unlikely related to the vacccine 4 8 7 3
Unsolicited AEs possibly related to the vacccine 5 4 1 1
Unsolicited AEs probably related to the vaccine 0 0 0 0
Unsolicited AEs definately related to the vaccine 2 1 0 0
Mild unsolicited AEs 15 16 10 4
Moderate unsolicited AEs 3 4 1 5
Severe unsolicited AEs 1 3 2 0
Severe Adverse Events 2 3 0 0
11.Other Pre-specified Outcome
Title Percentage of Participants Who Tested Positive for Influenza Strains
Hide Description During the influenza season (Dec 2016 to March 2017), fully vaccinated subjects will contact the trial center immediately if they feel unwell for 24h, with a sudden onset of flu-like symptoms. The medical staff will arrange for a nasopharyngeal swab to be performed if the subject has at least one respiratory (cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache) and one systemic symptom (fever, malaise, headache and myalgia (muscle and joint pain). Swabs should be taken from the reported subjects within 3 days from the trial center being contacted or within 4 days of the onset of symptoms, whatever time is shorter.
Time Frame For up to 4 months during the influenza season
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set includes subjects that completed vaccination and provided samples to measure immunogenicity data prevaccination (day 0) and at least one time point post vaccination (day 42 or day 180)
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Measure Type: Number
Unit of Measure: percentage of subjects
positive for influenza A strains 5.2 7.8 6.3 19.2
positive for influenza B strains 0.0 2.0 3.1 3.8
positive for influenza H1 strains 0.0 0.0 0.0 0.0
positive for influenza H3 strains 5.2 7.8 6.3 19.2
positive for any influenza strain 5.2 9.8 9.4 23.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Differences in the infection rates against any of the strains tested between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.662
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Differences in the infection rates against any of the strains tested between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.168
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
12.Other Pre-specified Outcome
Title Severity of Symptoms in RT-PCR Influenza-confirmed Subjects.
Hide Description Subjects recorded daily influenza symptoms from December 2016 up to March 2017. Subjects with a sudden onset of at least one respiratory and one systemic symptom were swabbed. If the results were positive for influenza then the symptoms were included in the analysis. The duration of symptoms was recorded as the number of symptomatic days during the influenza episode. Fever (≥38oC), malaise, headache, myalgia (muscle and joint pain), cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache were scored on a severity scale of 0 to 3 (0: no symptom, 1: mild, 2: moderate, 3: severe). The daily severity score was the sum of the severity score for all symptoms listed above on a single day. The total score was the sum of all daily scores during the influenza episode. The peak score was the highest daily score during the influenza episode. The average score was the total score divided by the number of days the influenza episode lasted.
Time Frame Symptoms experienced during an influenza infection episode, approximately 7-10 days.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: Full Analysis Set includes subjects that completed vaccination and provided samples to assess immunogenicity at pre-vaccination (day 0) and at least one post-vaccination time point (day 42 or day 180).
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Mean (Standard Error)
Unit of Measure: units on a scale
total symptom score 113.67  (50.87) 30.80  (8.46) 57.33  (13.28) 55.17  (12.96)
total symptom peak 17.67  (3.48) 13.80  (1.16) 15.33  (1.20) 16.50  (2.73)
average severity symptom score 10.63  (1.13) 10.92  (1.61) 8.59  (1.44) 13.76  (2.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Other Statistical Analysis The study was not powered to detected statistical significant differences in this outcome.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Other Statistical Analysis Study not powered to detect statistically significant differences
13.Other Pre-specified Outcome
Title Duration of Influenza Symptoms in RT-PCR Confirmed Infected Subjects.
Hide Description Subjects recorded daily influenza symptoms from December 2016 up to March 2017. Subjects with a sudden onset of at least one respiratory and one systemic symptom were swabbed. If the results were positive for influenza then the symptoms were included in the analysis. The duration of symptoms was recorded as the number of symptomatic days during the influenza episode. The following symptoms were recorded: fever (≥38oC), malaise, headache, myalgia (muscle and joint pain), cough, sore throat, shortness of breath, runny nose, stuffy nose, sneezing and earache.
Time Frame During an influenza episode
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population: subjects that completed the vaccination and had immunogenicity data at pre-vaccination and at least one time point post-vaccination.
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description:

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Overall Number of Participants Analyzed 58 51 32 26
Mean (Standard Error)
Unit of Measure: days
11.67  (5.61) 3.20  (1.07) 7.33  (2.19) 4.00  (0.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison in the duration of symptoms between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.513
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the duration of symptoms between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of total symptom score between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.513
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the total symptom score between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.200
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the symptom peak between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.658
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the symptom peak between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.640
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Non-adjuvanted Placebo
Comments Comparison of the average symptom score between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.127
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Adjuvanted Placebo
Comments Comparison of the average symptom score between treatment group and corresponding placebo.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
14.Post-Hoc Outcome
Title Effect of Influenza Vaccination in Previous 2 Years on Immunogenicity
Hide Description Antigen specific responders in FLU-v vaccinated arms compared to combined placebo group, grouped into those who had recieved an influenza vaccination within the previous 2 years and those who had not ever received a previous influenza vaccination. Responders were defined as those having a ≥2-fold increase in response in IFN-gamma secretion by peripheral blood mononuclear cells from day 0 to day 42 or day 180, as measured by enzyme-linked immunosorbent assay. The combined placebo group includes participants randomly assigned to adjuvanted placebo and those assigned to nonadjuvanted placebo.
Time Frame day 0 to day 42, day 0 to day 180
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title 2x Non-adjuvanted FLU-v, Previous Vaccination Within 2 Years 1x Adjuvanted FLU-v, Previous Vaccination Within 2 Years Combined Placebo, Previous Vaccination Within 2 Years 2x Non-adjuvanted FLU-v, no Previous Vaccination 1x Adjuvanted FLU-v, no Previous Vaccination Combined Placebo, no Previous Vaccination
Hide Arm/Group Description:
participants who had received an influenza vaccination in the previous 2 years, and who received FLU-v on Day 0 and Day 21 FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

participants who had received an influenza vaccination in the previous 2 years, and who received adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

participants who had received an influenza vaccination in the previous 2 years, and who received either non-adjuvanted placebo or adjuvanted placebo

Non-adjuvanted Placebo: saline solution (0.5ml) on Day 0 and Day 21

Adjuvanted Placebo: Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Participants who had not ever previously received an influenza vaccination, and who received FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

participants who had not ever previously received an influenza vaccination, and who received adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

participants who had not ever previously received an influenza vaccination, and who received either non-adjuvanted placebo or adjuvanted placebo

Non-adjuvanted Placebo: saline solution (0.5ml) on Day 0 and Day 21

Adjuvanted Placebo: Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Overall Number of Participants Analyzed 14 18 16 37 25 33
Measure Type: Count of Participants
Unit of Measure: Participants
Responders on day 42 Number Analyzed 12 participants 15 participants 13 participants 31 participants 21 participants 24 participants
6
  50.0%
13
  86.7%
6
  46.2%
20
  64.5%
21
 100.0%
10
  41.7%
Responders on day 180 Number Analyzed 10 participants 15 participants 13 participants 33 participants 21 participants 25 participants
5
  50.0%
13
  86.7%
8
  61.5%
15
  45.5%
21
 100.0%
15
  60.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Previous Vaccination Within 2 Years, Combined Placebo, Previous Vaccination Within 2 Years
Comments comparison between groups on day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Previous Vaccination Within 2 Years, Combined Placebo, Previous Vaccination Within 2 Years
Comments comparison between groups on day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, Previous Vaccination Within 2 Years, Combined Placebo, Previous Vaccination Within 2 Years
Comments comparison between groups on day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, Previous Vaccination Within 2 Years, Combined Placebo, Previous Vaccination Within 2 Years
Comments comparison between groups on day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.198
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, no Previous Vaccination, Combined Placebo, no Previous Vaccination
Comments comparison between groups on day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, no Previous Vaccination, Combined Placebo, no Previous Vaccination
Comments comparison of groups on day 42
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 2x Non-adjuvanted FLU-v, no Previous Vaccination, Combined Placebo, no Previous Vaccination
Comments comparison of groups on day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 1x Adjuvanted FLU-v, no Previous Vaccination, Combined Placebo, no Previous Vaccination
Comments comparisons between groups on day 180
Type of Statistical Test Other
Comments inequality test
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame From vaccination to study completion (approx. 7 months)
Adverse Event Reporting Description

Solicited Adverse Events were collected for 21 days after each vaccination. Subjects had to fill in the AEs diary card daily and return to the clinic on the next scheduled visit.

Unsolicited Adverse Events and Severe Adverse Events were collected at any time during the study directly to the PI or study doctor.

 
Arm/Group Title 2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Hide Arm/Group Description

FLU-v on Day 0 and Day 21

FLU-v: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH

adjuvanted FLU-v on Day 0, saline (0.5mL) on Day 21

adjuvanted FLU-v: Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

saline solution (0.5ml) on Day 0 and Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo on Day 0, saline (0.5mL) on Day 21

Saline: Subcutaneous injection in the upper arm with 0.5ml of saline

Adjuvanted placebo: Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection

All-Cause Mortality
2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/58 (0.00%)      0/57 (0.00%)      0/32 (0.00%)      0/27 (0.00%)    
Hide Serious Adverse Events
2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/58 (3.45%)      2/57 (3.51%)      0/32 (0.00%)      0/27 (0.00%)    
Cardiac disorders         
Myocardial Infarction * 1  1/58 (1.72%)  1 0/57 (0.00%)  0 0/32 (0.00%)  0 0/27 (0.00%)  0
Injury, poisoning and procedural complications         
upper limb fracture * 1  0/58 (0.00%)  0 1/57 (1.75%)  1 0/32 (0.00%)  0 0/27 (0.00%)  0
Psychiatric disorders         
Depression * 1  0/58 (0.00%)  0 1/57 (1.75%)  1 0/32 (0.00%)  0 0/27 (0.00%)  0
Alcohol problem * 1  0/58 (0.00%)  0 1/57 (1.75%)  1 0/32 (0.00%)  0 0/27 (0.00%)  0
Surgical and medical procedures         
Abdominal hernia repair * 1  1/58 (1.72%)  1 0/57 (0.00%)  0 0/32 (0.00%)  0 0/27 (0.00%)  0
1
Term from vocabulary, MedDRA (Unspecified)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
2x Non-adjuvanted FLU-v 1x Adjuvanted FLU-v Non-adjuvanted Placebo Adjuvanted Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   41/58 (70.69%)      50/57 (87.72%)      27/32 (84.38%)      24/27 (88.89%)    
Blood and lymphatic system disorders         
Lymphadenopathy  1  7/58 (12.07%)  8 4/57 (7.02%)  4 3/32 (9.38%)  4 4/27 (14.81%)  4
Gastrointestinal disorders         
diarrhoea  1  6/58 (10.34%)  8 8/57 (14.04%)  9 4/32 (12.50%)  4 2/27 (7.41%)  2
Vomiting  1  3/58 (5.17%)  3 5/57 (8.77%)  6 2/32 (6.25%)  2 0/27 (0.00%)  0
Abdominal pain  1  7/58 (12.07%)  7 7/57 (12.28%)  8 1/32 (3.13%)  2 2/27 (7.41%)  2
General disorders         
Fatigue  1  14/58 (24.14%)  16 17/57 (29.82%)  25 11/32 (34.38%)  12 6/27 (22.22%)  6
Influenza like illness * 1  11/58 (18.97%)  12 18/57 (31.58%)  19 10/32 (31.25%)  11 9/27 (33.33%)  12
Injection site erythema  1  13/58 (22.41%)  15 38/57 (66.67%)  40 0/32 (0.00%)  0 6/27 (22.22%)  6
Injection site pain  1  4/58 (6.90%)  6 39/57 (68.42%)  46 4/32 (12.50%)  4 11/27 (40.74%)  12
Injection site swelling  1  6/58 (10.34%)  7 38/57 (66.67%)  39 0/32 (0.00%)  0 7/27 (25.93%)  7
Injection site warmth  1  7/58 (12.07%)  9 29/57 (50.88%)  30 1/32 (3.13%)  1 6/27 (22.22%)  7
Injection site pruritus  1  9/58 (15.52%)  10 22/57 (38.60%)  23 0/32 (0.00%)  0 10/27 (37.04%)  14
Injection site induration  1  16/58 (27.59%)  18 49/57 (85.96%)  49 0/32 (0.00%)  0 10/27 (37.04%)  11
Haematoma at Injection Site  1  5/58 (8.62%)  6 19/57 (33.33%)  19 0/32 (0.00%)  0 5/27 (18.52%)  5
Infections and infestations         
Upper respiratory tract infection * 1  14/58 (24.14%)  15 14/57 (24.56%)  15 13/32 (40.63%)  14 6/27 (22.22%)  6
Herpes simplex  1  2/58 (3.45%)  2 2/57 (3.51%)  2 3/32 (9.38%)  3 1/27 (3.70%)  1
Metabolism and nutrition disorders         
Decreased apetite  1  1/58 (1.72%)  1 11/57 (19.30%)  12 0/32 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders         
arthralgia  1  4/58 (6.90%)  5 5/57 (8.77%)  6 1/32 (3.13%)  1 0/27 (0.00%)  0
Back pain  1  5/58 (8.62%)  5 5/57 (8.77%)  7 6/32 (18.75%)  7 2/27 (7.41%)  2
Myalgia  1  11/58 (18.97%)  12 9/57 (15.79%)  12