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Sanofi H1N1 Influenza Vaccine Administered at Different Dose Levels With and Without AS03 Adjuvant in Healthy Adult and Elderly Populations

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00963157
First received: August 20, 2009
Last updated: December 4, 2014
Last verified: January 2011
Results First Received: November 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Influenza
Interventions: Drug: AS03
Biological: Influenza Virus Vaccine, Monovalent A/H1N1 A/California/7/2009 NYMC X-179A

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were healthy adults age 18 and older recruited from existing volunteer populations and from the communities at large around the clinical sites. Participants were enrolled between 24Sep2009 and 16Nov2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
3.75 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 3.75 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 7.5 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine Unadjuvanted Participants received 7.5 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
15 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 15 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
15 mcg H1N1 Vaccine Unadjuvanted Participants received 15 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.

Participant Flow:   Overall Study
    3.75 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine Unadjuvanted   15 mcg H1N1 Vaccine + AS03 Adjuvant   15 mcg H1N1 Vaccine Unadjuvanted
STARTED   156   163   160   157   153 
COMPLETED   151   159   155   150   151 
NOT COMPLETED   5   4   5   7   2 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
3.75 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 3.75 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 7.5 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine Unadjuvanted Participants received 7.5 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
15 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 15 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
15 mcg H1N1 Vaccine Unadjuvanted Participants received 15 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
Total Total of all reporting groups

Baseline Measures
   3.75 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine Unadjuvanted   15 mcg H1N1 Vaccine + AS03 Adjuvant   15 mcg H1N1 Vaccine Unadjuvanted   Total 
Overall Participants Analyzed 
[Units: Participants]
 156   163   160   157   153   789 
Age 
[Units: Participants]
           
<=18 years   0   0   0   0   0   0 
Between 18 and 65 years   107   111   110   109   107   544 
>=65 years   49   52   50   48   46   245 
Age 
[Units: Years]
Mean (Standard Deviation)
 51.3  (17.6)   51.7  (18.0)   51.6  (17.8)   50.1  (18.3)   52.1  (18.6)   51.4  (18.0) 
Gender 
[Units: Participants]
           
Female   89   84   93   85   72   423 
Male   67   79   67   72   81   366 
Region of Enrollment 
[Units: Participants]
           
United States   156   163   160   157   153   789 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 8 days after the first H1N1 vaccination ]

2.  Primary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 21 days after the first H1N1 vaccination ]

3.  Primary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 8 days after the first H1N1 vaccination ]

4.  Primary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 21 days after the first H1N1 vaccination ]

5.  Primary:   Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs)   [ Time Frame: Day 0 through Day 365 after the last vaccination ]

6.  Primary:   Number of Participants With Hematology Laboratory Adverse Events After the First Vaccination   [ Time Frame: 8-10 days after first vaccination ]

7.  Primary:   Number of Participants With Hematology Laboratory Adverse Events After the Second Vaccination   [ Time Frame: 8-10 days after second vaccination ]

8.  Primary:   Number of Participants With Chemistry Laboratory Adverse Events After the First Vaccination   [ Time Frame: 8-10 days after first vaccination ]

9.  Primary:   Number of Participants With Chemistry Laboratory Adverse Events After the Second Vaccination   [ Time Frame: 8-10 days after second vaccination ]

10.  Primary:   Number of Participants Reporting Solicited Subjective Systemic Reactions After the First Vaccination   [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]

11.  Primary:   Number of Participants Reporting Solicited Subjective Systemic Reactions After the Second Vaccination   [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]

12.  Primary:   Number of Participants Reporting Fever After the First Vaccination   [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]

13.  Primary:   Number of Participants Reporting Fever After the Second Vaccination   [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]

14.  Primary:   Number of Participants Reporting Solicited Subjective Local Reactions After the First Vaccination   [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]

15.  Primary:   Number of Participants Reporting Solicited Subjective Local Reactions After the Second Vaccination   [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]

16.  Primary:   Number of Participants Reporting Solicited Quantitative Local Reactions After the First Vaccination   [ Time Frame: Within 8 days (Day 0-7) post first vaccination ]

17.  Primary:   Number of Participants Reporting Solicited Quantitative Local Reactions After the Second Vaccination   [ Time Frame: Within 8 days (Day 0-7) post second vaccination ]

18.  Primary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 8 after the first vaccination ]

19.  Primary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 21 after the first vaccination ]

20.  Primary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 8 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 8 after the first vaccination ]

21.  Primary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the First Dose of H1N1 Vaccine   [ Time Frame: Day 21 after the first vaccination ]

22.  Secondary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 8 after the second vaccination ]

23.  Secondary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 21 after the second vaccination ]

24.  Secondary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 180 after the second vaccination ]

25.  Secondary:   Number of Participants Age 18 to 64 Years With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 270 after the second vaccination ]

26.  Secondary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 8 after the second vaccination ]

27.  Secondary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 21 after the second vaccination ]

28.  Secondary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 180 after the second vaccination ]

29.  Secondary:   Number of Participants Age 65 Years and Older With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer of 1:40 or Greater Against the H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 270 after the second vaccination ]

30.  Secondary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 8 days after the second H1N1 vaccination ]

31.  Secondary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 21 days after the second H1N1 vaccination ]

32.  Secondary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 180 days after the second H1N1 vaccination ]

33.  Secondary:   Number of Participants Age 18 to 64 Years With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 270 days after the second H1N1 vaccination ]

34.  Secondary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 8 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 8 days after the second H1N1 vaccination ]

35.  Secondary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 21 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 21 days after the second H1N1 vaccination ]

36.  Secondary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 180 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 180 days after the second H1N1 vaccination ]

37.  Secondary:   Number of Participants Age 65 Years and Older With 4-fold or Greater Hemagglutination Inhibition Assay (HAI) Antibody Titer Increases Against the Influenza H1N1 2009 Virus 270 Days Following the Second Dose of H1N1 Vaccine   [ Time Frame: Day 0 prior to vaccination and 270 days after the second H1N1 vaccination ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Solicited events were collected for 8 days after each vaccination, unsolicited events through 21 days after last vaccination, and serious adverse events and new onset chronic medical conditions through 365 days after last vaccination.
Additional Description For events solicited on a Memory Aid in the 8 days after vaccination, a participant was considered to have one event if it was reported as experienced at any time in the 8 day period.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
3.75 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 3.75 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 7.5 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
7.5 mcg H1N1 Vaccine Unadjuvanted Participants received 7.5 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.
15 mcg H1N1 Vaccine + AS03 Adjuvant Participants received 15 mcg H1N1 vaccine plus AS03 adjuvant on Day 0 and Day 21.
15 mcg H1N1 Vaccine Unadjuvanted Participants received 15 mcg H1N1 vaccine unadjuvanted on Day 0 and Day 21.

Other Adverse Events
    3.75 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine + AS03 Adjuvant   7.5 mcg H1N1 Vaccine Unadjuvanted   15 mcg H1N1 Vaccine + AS03 Adjuvant   15 mcg H1N1 Vaccine Unadjuvanted
Total, other (not including serious) adverse events           
# participants affected / at risk   147/156 (94.23%)   157/163 (96.32%)   124/160 (77.50%)   146/157 (92.99%)   130/153 (84.97%) 
Gastrointestinal disorders           
Nausea † 1           
# participants affected / at risk   22/156 (14.10%)   19/163 (11.66%)   11/160 (6.88%)   19/157 (12.10%)   15/153 (9.80%) 
# events   28   19   12   22   15 
General disorders           
Injection site haematoma * 1           
# participants affected / at risk   10/156 (6.41%)   4/163 (2.45%)   9/160 (5.63%)   5/157 (3.18%)   8/153 (5.23%) 
# events   10   4   10   5   8 
Pyrexia † 1           
# participants affected / at risk   8/156 (5.13%)   7/163 (4.29%)   0/160 (0.00%)   9/157 (5.73%)   0/153 (0.00%) 
# events   10   8   0   9   0 
Feeling hot † 1           
# participants affected / at risk   35/156 (22.44%)   35/163 (21.47%)   11/160 (6.88%)   44/157 (28.03%)   15/153 (9.80%) 
# events   42   43   11   54   18 
Malaise † 1           
# participants affected / at risk   66/156 (42.31%)   67/163 (41.10%)   37/160 (23.13%)   61/157 (38.85%)   44/153 (28.76%) 
# events   89   82   46   84   51 
Chills † 1 [4]           
# participants affected / at risk   29/156 (18.59%)   28/163 (17.18%)   7/160 (4.38%)   30/157 (19.11%)   17/153 (11.11%) 
# events   36   33   8   32   17 
Chills † 1 [5]           
# participants affected / at risk   17/156 (10.90%)   19/163 (11.66%)   6/160 (3.75%)   22/157 (14.01%)   7/153 (4.58%) 
# events   21   19   6   23   7 
Injection site pain † 1           
# participants affected / at risk   101/156 (64.74%)   117/163 (71.78%)   33/160 (20.63%)   102/157 (64.97%)   47/153 (30.72%) 
# events   163   178   41   156   63 
Tenderness † 1 [6]           
# participants affected / at risk   138/156 (88.46%)   141/163 (86.50%)   52/160 (32.50%)   128/157 (81.53%)   70/153 (45.75%) 
# events   226   242   74   215   106 
Injection site erythema † 1           
# participants affected / at risk   54/156 (34.62%)   52/163 (31.90%)   51/160 (31.87%)   63/157 (40.13%)   53/153 (34.64%) 
# events   69   65   63   84   70 
Injection site swelling (functional grading) † 1 [7]           
# participants affected / at risk   46/156 (29.49%)   36/163 (22.09%)   33/160 (20.63%)   47/157 (29.94%)   37/153 (24.18%) 
# events   59   47   44   58   47 
Injection site swelling (measured) † 1 [7]           
# participants affected / at risk   48/156 (30.77%)   40/163 (24.54%)   37/160 (23.13%)   51/157 (32.48%)   42/153 (27.45%) 
# events   63   47   47   62   51 
Infections and infestations           
Upper respiratory tract infection * 1           
# participants affected / at risk   15/156 (9.62%)   17/163 (10.43%)   20/160 (12.50%)   16/157 (10.19%)   22/153 (14.38%) 
# events   18   18   22   17   25 
Investigations           
Blood pressure systolic increased * 1           
# participants affected / at risk   2/156 (1.28%)   3/163 (1.84%)   3/160 (1.88%)   8/157 (5.10%)   5/153 (3.27%) 
# events   2   3   3   8   5 
Musculoskeletal and connective tissue disorders           
Myalgia † 1           
# participants affected / at risk   55/156 (35.26%)   67/163 (41.10%)   22/160 (13.75%)   60/157 (38.22%)   32/153 (20.92%) 
# events   70   82   23   80   38 
Arthralgia † 1           
# participants affected / at risk   22/156 (14.10%)   27/163 (16.56%)   9/160 (5.63%)   26/157 (16.56%)   14/153 (9.15%) 
# events   24   28   10   31   18 
Nervous system disorders           
Headache † 1           
# participants affected / at risk   59/156 (37.82%)   68/163 (41.72%)   54/160 (33.75%)   47/157 (29.94%)   46/153 (30.07%) 
# events   75   85   62   66   59 
Respiratory, thoracic and mediastinal disorders           
Oropharyngeal pain * 1           
# participants affected / at risk   4/156 (2.56%)   8/163 (4.91%)   8/160 (5.00%)   3/157 (1.91%)   6/153 (3.92%) 
# events   4   10   8   3   6 
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (14.0)
[4] Solicited as "chills"
[5] Solicited as "shivering"
[6] Tenderness was solicited as a reaction at the vaccination site.
[7] Injection site swelling was solicited separately for functional grading of impact on daily activities and as a measured reaction.



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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