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: April 11, 2013
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: Biological: Inactivated H1N1 Vaccine
Biological: AS03

  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  
Number of Participants  
[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     157/163     124/160     146/157     130/153  
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 (31.88%)     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.



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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Lisa Jackson, MD, MPH
Organization: Group Health Research Institute
phone: 206-442-5216


Publications of Results:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00963157     History of Changes
Other Study ID Numbers: 09-0058, N01AI80004C
Study First Received: August 20, 2009
Results First Received: November 10, 2011
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government
United States: Food and Drug Administration