Safety, Tolerability and Immunogenicity of Two Doses of Adjuvanted Monovalent Influenza Vaccine Administered to Healthy Adult and Elderly Subjects

This study has been completed.

Sponsor:

Collaborator:

Novartis Vaccines

Information provided by (Responsible Party):

Novartis

ClinicalTrials.gov Identifier:

NCT00841763

First received: February 10, 2009

Last updated: January 18, 2013

Last verified: January 2013

History of Changes

Results First Received: July 4, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Prevention
Condition:	Pandemic Influenza Disease
Interventions:	Biological: Placebo Biological: Trivalent influenza virus vaccine (TIV) Biological: Adjuvanted monovalent influenza virus vaccine (aH5N1) Biological: Adjuvanted trivalent influenza vaccine (aTIV)

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
Subjects were enrolled from 27 centers across Finland and Germany

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All subjects enrolled were included in the trial.

Reporting Groups

	Description
TIV + aH5N1 (18 to 60 Yrs)	First dose of trivalent influenza vaccine (TIV) followed by two doses of adjuvanted monovalent influenza virus vaccine (aH5N1)
PL+ aTIV (18 to 60 Yrs)	First dose of placebo (PL) followed by two doses of influenza virus vaccine (aTIV)
TIV + aH5N1 (>60 Yrs)	First dose of trivalent influenza vaccine (TIV) followed by two doses of adjuvanted monovalent influenza virus vaccine (aH5N1)
PL + aTIV (>60 Yrs)	First dose of placebo (PL) followed by two doses of influenza virus vaccine (aTIV)

Participant Flow: Overall Study

	TIV + aH5N1 (18 to 60 Yrs)	PL+ aTIV (18 to 60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL + aTIV (>60 Yrs)
STARTED	2691	681	219	56
COMPLETED	2529	624	211	53
NOT COMPLETED	162	57	8	3
Withdrawal by Subject	60	17	4	1
Adverse Event	9	10	3	2
Lost to Follow-up	63	25	0	0
Protocol Violation	20	3	1	0
Administrative Reasons	3	1	0	0
Unable to Classify	7	1	0	0

Baseline Characteristics

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Reporting Groups

	Description
TIV + aH5N1	First dose of trivalent influenza vaccine (TIV) followed by two doses of adjuvanted monovalent influenza virus vaccine (aH5N1).
PL+ aTIV	First dose of placebo (PL) followed by two doses of influenza virus vaccine (aTIV)
Total	Total of all reporting groups

Baseline Measures

	TIV + aH5N1	PL+ aTIV	Total
Number of Participants [units: participants]	2911	735	3646
Age, Customized ^[1] [units: years] Mean ± Standard Deviation
<= 60 years	40.7 ± 11.6	40.5 ± 12.0	40.7 ± 11.7
>60 years (N=196, 50)	61.9 ± 1.4	62.1 ± 1.8	61.9 ± 1.5
Gender, Customized [units: Subjects]
Female (<=60 yrs)	1502	388	1890
Male(<=60 yrs)	1190	291	1481
Female (>60 yrs; N= 109; 28)	109	28	137
Male(>60 yrs; N= 110, 28)	110	28	138

[1]	The number of subjects analyzed is not consistent with the Participant Flow module due to randomization errors. The enrolled set as randomized is reported in the Participant Flow Module but in the Baseline Measure module, the enrolled set as treated is reported (2 randomization errors so 2 subjects were changed from the TIV+aH5N1 group to the PL+aTIV group). Moreover, a subset to the enrolled population as treated excluded the one subject who was not vaccinated.

[1]

The number of subjects analyzed is not consistent with the Participant Flow module due to randomization errors. The enrolled set as randomized is reported in the Participant Flow Module but in the Baseline Measure module, the enrolled set as treated is reported (2 randomization errors so 2 subjects were changed from the TIV+aH5N1 group to the PL+aTIV group). Moreover, a subset to the enrolled population as treated excluded the one subject who was not vaccinated.

Outcome Measures

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1. Primary:

Number of Participants With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine [ Time Frame: Up to 7 days after each vaccination ]

Show Outcome Measure 1

2. Secondary:

The Number of Participants With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine as Compared With the Adjuvanted Seasonal Trivalent Influenza Vaccine [ Time Frame: Up to 7 days after each vaccination ]

Show Outcome Measure 2

3. Secondary:

Geometric Mean Titers After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain [ Time Frame: 3 weeks after vaccination (day 22, day 43, day 64) ]

Show Outcome Measure 3

4. Secondary:

Geometric Mean Areas After Two Doses of the Adjuvanted Monovalent Influenza Virus Vaccine (aH5N1) [ Time Frame: 3 weeks after vaccination (day22, day 43, day 64) ]

Show Outcome Measure 4

5. Secondary:

Geometric Mean Ratios After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain [ Time Frame: 3 weeks after vaccination (day 43/day22, day 64/day43) ]

Show Outcome Measure 5

6. Secondary:

Percentages of Participants Achieving Geometric Mean Titers ≥ 40 and Geometric Mean Areas ≥ 25mm2, After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain) [ Time Frame: 3 weeks after vaccination (day 22, day 43, day 64) ]

Show Outcome Measure 6

7. Secondary:

Percentages of Participants Achieving Seroconversion or Significant Increase in Antibody Titer After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain [ Time Frame: 3 weeks after vaccination (day 43/day22 and day 64/day22) ]

Show Outcome Measure 7

8. Secondary:

Geometric Mean Titers After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain. [ Time Frame: 3 weeks after vaccination (day 22, day 43, day 64) ]

Show Outcome Measure 8

9. Secondary:

Geometric Mean Areas After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain. [ Time Frame: 3 weeks after vaccination (day 22, day 43, day 64) ]

Show Outcome Measure 9

10. Secondary:

Geometric Mean Ratios After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain. [ Time Frame: 3 weeks after vaccination (day 43/day 22 and day 64/day 22) ]

Show Outcome Measure 10

11. Secondary:

Percentages of Participants Achieving Geometric Mean Titers ≥ 40 and Geometric Mean Areas ≥ 25mm2, After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain [ Time Frame: 3 weeks after vaccination (day 22, day 43, day 64) ]

Show Outcome Measure 11

12. Secondary:

Percentages of Participants Achieving Seroconversion or Significant Increase in Antibody Titers, After Two Doses of the Adjuvanted Pandemic H5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain. [ Time Frame: 3 weeks after vaccination (day 43/day 22 and day 64/day 22) ]

Show Outcome Measure 12

Serious Adverse Events

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Other Adverse Events

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More Information

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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:

	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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	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.
	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: Posting Director
Organization: Novartis Vaccines and Diagnostics
e-mail: RegistryContactVaccinesUS@novartis.com

Publications of Results:

Vesikari T, Forstén A, Herbinger KH, Cioppa GD, Beygo J, Borkowski A, Groth N, Bennati M, von Sonnenburg F. Safety and immunogenicity of an MF59(®)-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly. Vaccine. 2012 Feb 8;30(7):1388-96. Epub 2011 Dec 20.

Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT00841763 History of Changes
Other Study ID Numbers:	V87P13, 2008-003871-32
Study First Received:	February 10, 2009
Results First Received:	July 4, 2011
Last Updated:	January 18, 2013
Health Authority:	Germany: Paul-Ehrlich-Institut

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