CompletedNCT00841763Updated Apr 23, 2021Results posted

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

A Phase 3 interventional study of Placebo (PL) and Trivalent influenza virus vaccine (TIV) in Pandemic Influenza Disease, sponsored by Novartis. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-04-23.

Sponsored by Novartis · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 3,647
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The present study, phase III, randomized, controlled, observer-blind, multicenter study, will evaluate safety, tolerability and immunogenicity of two doses of an adjuvanted monovalent influenza vaccine compared with an adjuvanted interpandemic trivalent influenza vaccine in a population of healthy adult and elderly subjects.

Conditions studied

Pandemic Influenza Disease

Browse trials for

Influenza, Human 2,214

Keywords

virus
pandemic influenza
vaccine

In context

Influenza, Human

2,214 studies on the registry are indexed under Influenza, Human; 163 are open to participants now.

This study's enrollment of 3,647 is above the median of 238 across 1,853 interventional studies indexed under Influenza, Human.

Browse Influenza, Human studies →

Lead sponsor

Novartis is the lead sponsor of 703 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Subjects 18 years of age and older who were mentally competent and who had signed an informed consent form after having received a detailed explanation of the study protocol;
In good health as determined by:
1. medical history,
2. physical examination,
3. clinical judgment of the Investigator;
Able to understand and comply with all study procedures and to complete study diaries, could be contacted, and were available for study visits;

Exclusion criteria

Exclusion Criteria:

Receipt of another investigational agent within 4 weeks;
Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
Receipt of influenza vaccination for current season 2008/2009;
Experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) within the past 7 days;
Experienced fever (defined as axillary temperature ≥38.0°C) within 7 days prior to Visit 1;
Pregnant or breastfeeding;
Females of childbearing potential who were sexually active and had not used or did not plan or refused to use an acceptable method of birth control during the active phase of the study (at least up to three weeks after last vaccine injection);
Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis); diabetes mellitus type I and type II; diabetes relating to genetic defects/syndromes, diseases of the exocrine pancreas or infections; advanced arteriosclerotic disease; severe chronic obstructive pulmonary disease (COPD), i.e. GOLD stages 3 and 4; acute or progressive hepatic disease and renal disease; congestive heart failure; Body Mass Index (BMI) ≥35 kg/m2 where BMI reflects obesity and not high muscle mass;
History of progressive or severe neurologic disorders, of any neurological symptoms or signs, or anaphylactic shock following administration of any study vaccine;
Bleeding diathesis;
Surgery planned during the study period;
Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccines;
Known or suspected impairment/alteration of immune function, for example, resulting from:
1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy) or other immunosuppressive agents within the past 60 days and for the full length of the study;
2. receipt of immunostimulants;
3. receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study;
4. suspected or known HIV infection or HIV-related disease;
Receipt of non study vaccines (with the exception of post-exposure vaccination in a medical emergency, e.g. hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
History of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
Members of research staff and their relatives;
Any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 3,647 participants (actual)

Study arms

Experimental
TIV + aH5N1
First dose of the non-adjuvanted trivalent influenza virus vaccine (TIV) followed by two doses of the adjuvanted monovalent influenza virus vaccine (aH5N1).
Biological: Trivalent influenza virus vaccine (TIV) · Biological: Adjuvanted monovalent influenza virus vaccine (aH5N1)
Active comparator
PL + aTIV
First dose of placebo (PL-saline) followed by two doses of the adjuvanted trivalent influenza virus vaccine (aTIV).
Biological: Placebo (PL) · Biological: Adjuvanted trivalent influenza virus vaccine (aTIV)

Interventions

BiologicalPlacebo (PL)
One dose of 0.5 ml IM injection of isotonic saline solution was administered in the deltoid muscle, preferably of the non-dominant arm.
BiologicalTrivalent influenza virus vaccine (TIV)
A single IM injection of a 0.5 ml dose of non-adjuvanted trivalent influenza virus vaccine administered in the deltoid muscle, preferably of the non-dominant arm.
BiologicalAdjuvanted monovalent influenza virus vaccine (aH5N1)
Two intramuscular (IM) injections of a 0.5 ml dose administered three weeks apart in the deltoid muscle.
BiologicalAdjuvanted trivalent influenza virus vaccine (aTIV)
Two IM injections of a 0.5 ml dose of adjuvanted trivalent influenza virus vaccine administered three weeks apart, in the deltoid muscle.

What researchers measure

Primary outcomes

Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.
To assess the safety and tolerability profile of two doses of the MF59-adjuvanted A/Vietnam/1194/2004 pandemic influenza vaccine (aH5N1), each containing 7.5 μg of H5N1 antigen in terms of the number of participants who reported local and systemic reactions up to 6 days after each vaccination per vaccination group.
Time frame: Up to 6 days after each vaccination.
Number of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.
To report safety data from a large enough number of subjects exposed to adjuvanted pandemic influenza vaccine aH5N1 capable of detecting rare adverse events (AEs), i.e. events occurring at a frequency of \<=0.1%, \& uncommon AEs in elderly, i.e. occurring at a frequency of \<=1% of subjects.
Time frame: Upto Day 224 post vaccination

Secondary outcomes

The Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine as Compared With the Adjuvanted Seasonal Trivalent Influenza Vaccine aTIV.
To evaluate the safety and tolerability profile of two doses of the adjuvanted pandemic H5N1 vaccine (aH5N1) as compared with the MF59-adjuvanted seasonal trivalent influenza vaccine (aTIV), in terms of the number of subjects who reported local and systemic reactions up to 6 days after each vaccination per vaccination group.
Time frame: Up to 6 days after each vaccination.
Geometric Mean Titers (GMTs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic H5N1 vaccine (aH5N1), each containing 7.5µg of H5N1 antigen, in terms of GMTs against the homologous A/Vietnam/1194/2004 strain, as determined by Hemagglutination Inhibition (HI) assay and Microneutralization (MN) assay.
Time frame: Day 22, Day 43, Day 64
Geometric Mean Areas (GMAs) After Two Doses of the Adjuvanted Pandemic Vaccine (aH5N1).
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, in terms of GMAs as determined by Single Radial Hemolysis (SRH) assay. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.
Time frame: Day 22, Day 43, Day 64
Geometric Mean Ratios (GMRs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5µg of H5N1 antigen,in terms of GMRs against the homologous A/Vietnam/1194/2004 strain, as determined by HI, MN and SRH assays.
Time frame: Day 43/Day 22, Day 64/Day 22
Percentages of Subjects With HI Titers ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving HI titers ≥ 40 and GMAs ≥ 25mm\^2, as determined by HI and SRH assays. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.
Time frame: Day 22, Day 43 and Day 64
Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titer After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving seroconversion or significant increase in antibody titer as measured by HI and SRH assays.
Time frame: Day 43/Day 22 and Day 64/Day 22
GMTs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5µg of H5N1 antigen, in terms of GMTs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by HI and MN assays.
Time frame: Day 22, Day 43 and Day 64
GMAs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, in terms of GMAs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by SRH assay. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.
Time frame: Day 22, Day 43 and Day 64
GMRs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, in terms of GMRs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by HI, MN and SRH assays.
Time frame: Day 43/Day 22 and Day 64/Day 22
Percentages of Subjects With HI ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 strain, in terms of percentages of subjects achieving HI titers ≥ 40 and GMAs ≥ 25mm\^2 as determined by HI and SRH assays. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Vaccine on Day 22, Day 43, Day 64.
Time frame: Day 22, Day 43 and Day 64
Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titers, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 strain, in terms of percentages of subjects achieving seroconversion or significant increase in antibody titer as measured by HI and SRH assays.
Time frame: Day 43/Day 22 and Day 64/Day 22)
Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5μg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving MN Titers ≥20, ≥ 40, ≥80 on Days 22, Day 43 and Day 64.
Time frame: Day 22, Day 43 and Day 64
Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5μg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 Strain, in terms of percentages of subjects achieving MN Titers ≥20, ≥ 40, ≥80 on Day 22, Day 43 and Day 64.
Time frame: Day 22, Day 43 and Day 64
Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Homologous Strains.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5μg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving at least a four-fold rise in MN antibody titer on Day 43 and Day 64, compared to Day 22.
Time frame: Day 43/Day 22 and Day 64/Day 22
Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Heterologous Strains.
To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5μg of H5N1 antigen, against Heterologous A/turkey/Turkey/1/2005 Strain, in terms of percentages of subjects achieving at least a four-fold rise in MN antibody titer on Day 43 and Day 64, compared to Day 22.
Time frame: Day 43/Day 22 and Day 64/Day 22
Number of Subjects Reporting Unsolicited AEs After Vaccination.
The number of subjects reporting any unsolicited AEs any, Possibly/probably related AEs, serious adverse events (SAEs), AEs leading to withdrawal (WD), AEs leading to death from Day 1 through Day 224 post vaccination.
Time frame: Day 1 through Day 224 post vaccination

Results

Posted Jan 18, 2013

Participant flow

Subjects were enrolled from 27 centers across Finland and Germany.

Participant flow — Overall Study
Milestone	TIV + aH5N1 (18-60 Yrs)	PL+ aTIV (18-60 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
Withdrew: Withdrawal by subject	60	17	4	1
Withdrew: Adverse event	9	10	3	2
Withdrew: Lost to follow-up	63	25	0	0
Withdrew: Protocol violation	20	3	1	0
Withdrew: Administrative reasons	3	1	0	0
Withdrew: Unable to classify	7	1	0	0

Outcome measures

PrimaryNumber of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.

To assess the safety and tolerability profile of two doses of the MF59-adjuvanted A/Vietnam/1194/2004 pandemic influenza vaccine (aH5N1), each containing 7.5 μg of H5N1 antigen in terms of the number of participants who reported local and systemic reactions up to 6 days after each vaccination per vaccination group.

Time frame:: Up to 6 days after each vaccination.
Reported as:: Number · Participants

Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.
Participants	TIV + aH5N1 (18-60 Yrs)	PL+ aTIV (18-60 Yrs)
Local reactions	1755	502
Injection site ecchymosis	237	78
Injection site erythema	652	206
Injection site induration	549	181
Injection site swelling	409	162
Injection site pain	1537	448
Systemic reactions	1387	386
Chills	342	118
Malaise	347	130
Myalgia	869	277
Arthralgia	188	79
Nausea	193	64
Headache	668	189
Sweating	237	658
Fatigue	638	188
Fever ≥ 38°C	28	12
Stayed at home	64	22
Analgesic Antipyretic medi. used	361	114

SecondaryThe Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine as Compared With the Adjuvanted Seasonal Trivalent Influenza Vaccine aTIV.

To evaluate the safety and tolerability profile of two doses of the adjuvanted pandemic H5N1 vaccine (aH5N1) as compared with the MF59-adjuvanted seasonal trivalent influenza vaccine (aTIV), in terms of the number of subjects who reported local and systemic reactions up to 6 days after each vaccination per vaccination group.

Time frame:: Up to 6 days after each vaccination.
Reported as:: Number · Subjects

The Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine as Compared With the Adjuvanted Seasonal Trivalent Influenza Vaccine aTIV.
Subjects	TIV + aH5N1 (18-60 Yrs)	PL+ aTIV (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL+ aTIV (>60 Yrs)
Local reactions	1755	502	115	30
Injection site ecchymosis (N= 2610,658,214,54)	237	78	23	7
Injection site erythema	652	206	45	14
Injection site induration (N= 2610,658,214,54)	549	181	22	10
Injection site swelling	409	162	22	6
Injection site pain (N= 2610,658,214,54)	1537	448	87	21
Systemic reactions	1387	386	95	26
Chills	342	118	29	10
Malaise (N= 2610,658,214,54)	347	130	25	6
Myalgia	869	277	59	16
Arthralgia (N= 2610,658,214,54)	188	79	15	5
Nausea	193	64	14	3
Headache (N= 2610,658,214,54)	668	189	38	10
Sweating	237	63	10	2
Fatigue (N= 2610,658,214,54)	638	188	27	7
Fever ≥38°C	28	12	1	1
Stayed at home	64	22	3	1
Analg. Antipyr. Medi. used	361	114	27	6

SecondaryGeometric Mean Titers (GMTs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic H5N1 vaccine (aH5N1), each containing 7.5µg of H5N1 antigen, in terms of GMTs against the homologous A/Vietnam/1194/2004 strain, as determined by Hemagglutination Inhibition (HI) assay and Microneutralization (MN) assay.

Time frame:: Day 22, Day 43, Day 64
Reported as:: Geometric mean · Titers

Geometric Mean Titers (GMTs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
Titers	TIV + aH5N1 (18-60 Yrs) HI Assay	TIV + aH5N1 (>60 Yrs) HI Assay	TIV + aH5N1 (18-60 Yrs) MN Assay	TIV + aH5N1 (>60 Yrs) MN Assay
Day 22 (baseline)	6.17 (5.58 to 6.83)	6.98 (6.21 to 7.85)	11 (10 to 11)	10 (9.97 to 11)
Day 43	14 (11 to 17)	15 (12 to 18)	17 (15 to 19)	17 (15 to 19)
Day 64	44 (34 to 56)	36 (28 to 45)	65 (56 to 77)	45 (39 to 53)

SecondaryGeometric Mean Areas (GMAs) After Two Doses of the Adjuvanted Pandemic Vaccine (aH5N1).

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, in terms of GMAs as determined by Single Radial Hemolysis (SRH) assay. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.

Time frame:: Day 22, Day 43, Day 64
Reported as:: Geometric mean · Areas (mm^2)

Geometric Mean Areas (GMAs) After Two Doses of the Adjuvanted Pandemic Vaccine (aH5N1).
Areas (mm^2)	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 22 (baseline)	11 (9.45 to 12)	13 (11 to 14)
Day 43	21 (18 to 24)	20 (18 to 23)
Day 64	43 (39 to 47)	37 (33 to 41)

SecondaryGeometric Mean Ratios (GMRs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5µg of H5N1 antigen,in terms of GMRs against the homologous A/Vietnam/1194/2004 strain, as determined by HI, MN and SRH assays.

Time frame:: Day 43/Day 22, Day 64/Day 22
Reported as:: Geometric mean · Ratios

Geometric Mean Ratios (GMRs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
Ratios	TIV + aH5N1 (18-60 Yrs) HI Assay	TIV + aH5N1 (>60 Yrs) HI Assay	TIV + aH5N1 (18-60 Yrs) MN Assay	TIV + aH5N1 (>60 Yrs) MN Assay	TIV + aH5N1 (18-60 Yrs) SRH Assay	TIV + aH5N1 (>60 Yrs) SRH Assay
Day 43 to Day 22 (N= 196,201,197,207,197,208)	2.25 (1.86 to 2.72)	2.14 (1.8 to 2.54)	1.58 (1.39 to 1.79)	1.63 (1.43 to 1.84)	1.95 (1.72 to 2.2)	1.57 (1.41 to 1.75)
Day 64 to Day 22	7.1 (5.52 to 9.14)	5.15 (4.15 to 6.4)	6.21 (5.29 to 7.29)	4.42 (3.79 to 5.15)	4.03 (3.54 to 4.59)	2.9 (2.53 to 3.31)

SecondaryPercentages of Subjects With HI Titers ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving HI titers ≥ 40 and GMAs ≥ 25mm\^2, as determined by HI and SRH assays. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Number · Percentages of subjects

Percentages of Subjects With HI Titers ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs) HI Titers ≥ 40	TIV + aH5N1 (>60 Yrs) HI Titers ≥ 40	TIV + H5N1 (18-60 Yrs) SRH Areas ≥ 25mm^2	TIV + aH5N1 (>60 Yrs) SRH Areas ≥ 25mm^2
Day 22 (baseline)	6 (3 to 10)	8 (5 to 12)	19 (14 to 26)	25 (20 to 32)
Day 43	30 (23 to 37)	31 (25 to 38)	48 (41 to 55)	46 (39 to 53)
Day 64	61 (53 to 67)	57 (50 to 64)	91 (87 to 95)	82 (76 to 87)

SecondaryPercentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titer After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.

Time frame:: Day 43/Day 22 and Day 64/Day 22
Reported as:: Number · Percentages of subjects

Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titer After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs) HI Titers	TIV + aH5N1 (>60 Yrs) HI Titers	TIV + aH5N1 (18-60 Yrs) SRH Areas	TIV + aH5N1 (>60 Yrs) SRH Areas
Day 43/Day 22	23 (18 to 30)	22 (16 to 28)	37 (30 to 44)	23 (17 to 29)
Day 64/Day 22	56 (49 to 63)	50 (43 to 57)	78 (72 to 84)	63 (56 to 69)

SecondaryGMTs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5µg of H5N1 antigen, in terms of GMTs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by HI and MN assays.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Geometric mean · Titers

GMTs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Titers	TIV + aH5N1 (18-60 Yrs) HI Assay	TIV + aH5N1 (>60 Yrs) HI Assay	TIV + aH5N1 (18-60 Yrs) MN Assay	TIV + aH5N1 (>60 Yrs) MN Assay
Day 22 (baseline)	6.03 (5.55 to 6.55)	6.85 (6.21 to 7.55)	11 (10 to 11)	11 (11 to 12)
Day 43	8.03 (7.07 to 9.12)	8.87 (7.69 to 10)	15 (13 to 17)	15 (13 to 16)
Day 64	12 (9.77 to 14)	12 (10 to 14)	30 (26 to 35)	23 (20 to 26)

SecondaryGMAs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, in terms of GMAs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by SRH assay. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Day 22, Day 43 and Day 64.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Geometric mean · Areas (mm^2)

GMAs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Areas (mm^2)	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 22 (baseline)	9.89 (8.82 to 11)	12 (10 to 13)
Day 43	14 (13 to 16)	14 (13 to 16)
Day 64	23 (21 to 26)	20 (18 to 23)

SecondaryGMRs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, in terms of GMRs against the heterologous A/turkey/Turkey/1/2005 strain, as determined by HI, MN and SRH assays.

Time frame:: Day 43/Day 22 and Day 64/Day 22
Reported as:: Geometric mean · Ratios

GMRs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Ratios	TIV + aH5N1 (18-60 Yrs) HI Assay	TIV + aH5N1 (>60 Yrs) HI Assay	TIV + aH5N1 (18-60 Yrs) MN Assay	TIV + aH5N1 (>60 Yrs) MN Assay	TIV + aH5N1 (18-60 Yrs) SRH Assay	TIV + aH5N1 (>60 Yrs) SRH Assay
Day 43/Day 22	1.33 (1.19 to 1.49)	1.29 (1.16 to 1.45)	1.39 (1.25 to 1.54)	1.29 (1.17 to 1.42)	1.44 (1.31 to 1.59)	1.25 (1.15 to 1.36)
Day 64/Day 22	1.92 (1.64 to 2.25)	1.79 (1.56 to 2.06)	2.77 (2.4 to 3.2)	2.01 (1.78 to 2.26)	2.37 (2.1 to 2.67)	1.74 (1.57 to 1.94)

SecondaryPercentages of Subjects With HI ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 strain, in terms of percentages of subjects achieving HI titers ≥ 40 and GMAs ≥ 25mm\^2 as determined by HI and SRH assays. GMA: For each vaccine group, least squares GMAs (for SRH data), associated 2-sided 95% confidence interval and median, minimal, and maximal titer values were determined for study Vaccine on Day 22, Day 43, Day 64.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Number · Percentages of subjects

Percentages of Subjects With HI ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs) HI Titers ≥ 40	TIV + aH5N1 (>60 Yrs) HI Titers ≥ 40	TIV + aH5N1 (18-60 Yrs) SRH Areas ≥ 25mm^2	TIV + aH5N1 (>60 Yrs) SRH Areas≥ 25mm^2
Day 22 (baseline)	3 (1 to 7)	5 (2 to 9)	16 (11 to 22)	23 (18 to 30)
Day 43	11 (7 to 16)	15 (10 to 20)	30 (24 to 37)	32 (26 to 39)
Day 64	23 (18 to 30)	25 (19 to 32)	59 (52 to 66)	48 (41 to 55)

SecondaryPercentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titers, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5µg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 strain, in terms of percentages of subjects achieving seroconversion or significant increase in antibody titer as measured by HI and SRH assays.

Time frame:: Day 43/Day 22 and Day 64/Day 22)
Reported as:: Number · Percentages of subjects

Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titers, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs) HI Titers	TIV + aH5N1 (>60 Yrs) HI Titers	TIV + aH5N1 (18-60 Yrs) SRH Areas	TIV + aH5N1 (>60 Yrs) SRH Areas
Day 43/Day 22	9 (5 to 13)	8 (5 to 12)	18 (13 to 24)	10 (6 to 14)
Day 64/Day 22	19 (14 to 25)	19 (14 to 25)	49 (42 to 56)	32 (26 to 39)

PrimaryNumber of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.

To report safety data from a large enough number of subjects exposed to adjuvanted pandemic influenza vaccine aH5N1 capable of detecting rare adverse events (AEs), i.e. events occurring at a frequency of \<=0.1%, \& uncommon AEs in elderly, i.e. occurring at a frequency of \<=1% of subjects.

Time frame:: Upto Day 224 post vaccination
Reported as:: Number · Participants

Number of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.
Participants	TIV + aH5N1 (18-60 Yrs)	PL+ aTIV (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL+ aTIV (>60 Yrs)
Number of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.	2692	679	219	56

SecondaryPercentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5μg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving MN Titers ≥20, ≥ 40, ≥80 on Days 22, Day 43 and Day 64.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Number · Percentages of subjects

Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 22 (MN titer ≥ 20)	3 (1 to 6)	2 (1 to 5)
Day 43 (MN titer ≥ 20)	27 (21 to 34)	25 (19 to 31)
Day 64 (MN titer ≥ 20)	79 (73 to 85)	72 (65 to 78)
Day 22 (MN titer ≥ 40)	2 (0 to 4)	1 (0 to 3)
Day 43 (MN titer ≥ 40)	16 (11 to 22)	19 (14 to 25)
Day 64 (MN titer ≥ 40)	67 (60 to 74)	57 (50 to 64)
Day 22 (MN titer ≥ 80)	1 (0 to 4)	0 (0 to 2)
Day 43 (MN titer ≥ 80)	9 (6 to 14)	13 (8 to 18)
Day 64 (MN titer ≥ 80)	50 (43 to 57)	33 (26 to 40)

SecondaryPercentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5μg of H5N1 antigen, against the heterologous A/turkey/Turkey/1/2005 Strain, in terms of percentages of subjects achieving MN Titers ≥20, ≥ 40, ≥80 on Day 22, Day 43 and Day 64.

Time frame:: Day 22, Day 43 and Day 64
Reported as:: Number · Percentages of subjects

Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 22 (MN titer≥20)	5 (2 to 8)	9 (6 to 14)
Day 43 (MN titer ≥ 20)	23 (17 to 29)	21 (15 to 27)
Day 64 (MN titer ≥ 20; N= 197, 208)	59 (52 to 66)	47 (40 to 54)
Day 22 (MN titer ≥ 40)	3 (1 to 7)	3 (1 to 7)
Day 43 (MN titer ≥ 40)	13 (8 to 18)	14 (9 to 19)
Day 64 (MN titer ≥ 40)	39 (32 to 46)	30 (24 to 37)
Day 22 (MN titer ≥ 80)	2 (1 to 5)	0.012 (0.012 to 3)
Day 43 (MN titer ≥ 80)	8 (4 to 12)	6 (3 to 10)
Day 64 (MN titer ≥ 80)	19 (14 to 26)	12 (8 to 17)

SecondaryPercentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Homologous Strains.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine aH5N1, each containing 7.5μg of H5N1 antigen, against the homologous A/Vietnam/1194/2004 strain, in terms of percentages of subjects achieving at least a four-fold rise in MN antibody titer on Day 43 and Day 64, compared to Day 22.

Time frame:: Day 43/Day 22 and Day 64/Day 22
Reported as:: Number · Percentages of subjects

Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Homologous Strains.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 43/Day 22	14 (10 to 20)	18 (13 to 24)
Day 64/Day 22	65 (58 to 72)	55 (48 to 62)

SecondaryPercentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Heterologous Strains.

To evaluate the immunogenicity of two doses of the adjuvanted pandemic vaccine (aH5N1), each containing 7.5μg of H5N1 antigen, against Heterologous A/turkey/Turkey/1/2005 Strain, in terms of percentages of subjects achieving at least a four-fold rise in MN antibody titer on Day 43 and Day 64, compared to Day 22.

Time frame:: Day 43/Day 22 and Day 64/Day 22
Reported as:: Number · Percentages of subjects

Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Heterologous Strains.
Percentages of subjects	TIV + aH5N1 (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)
Day 43/Day 22	9 (5 to 14)	9 (6 to 14)
Day 64/Day 22	36 (29 to 43)	25 (19 to 31)

SecondaryNumber of Subjects Reporting Unsolicited AEs After Vaccination.

The number of subjects reporting any unsolicited AEs any, Possibly/probably related AEs, serious adverse events (SAEs), AEs leading to withdrawal (WD), AEs leading to death from Day 1 through Day 224 post vaccination.

Time frame:: Day 1 through Day 224 post vaccination
Reported as:: Number · Subjects

Number of Subjects Reporting Unsolicited AEs After Vaccination.
Subjects	TIV + aH5N1 (18-60 Yrs)	PL + aTIV (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL + aTIV (>60 Yrs)
Any AEs	1329	335	103	29
SAEs	45	10	4	3
At least possibly related AEs	357	103	25	13
AEs Leading to Premature Withdrawal	4	4	2	1
Deaths	0	0	1	0

Adverse events

Collected over Throughout the study ie. Day 1 to Day 224. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
TIV + aH5N1 (18-60 Yrs)	—	40/2,680 (1.5%)	2,301/2,680 (85.9%)
PL + aTIV (18-60 Yrs)	—	9/676 (1.3%)	590/676 (87.3%)
TIV + aH5N1 (>60 Yrs)	—	1/222 (0.5%)	176/222 (79.3%)
PL + aTIV (>60 Yrs)	—	2/56 (3.6%)	45/56 (80.4%)

Most frequent serious events

Showing 10 of 53

Most frequent serious events
Event	TIV + aH5N1 (18-60 Yrs)	PL + aTIV (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL + aTIV (>60 Yrs)
PneumoniaInfections and infestations	1/2680	0/676	0/222	1/56
Humerus fractureInjury, poisoning and procedural complications	0/2680	0/676	0/222	1/56
Cerebral infractionNervous system disorders	0/2680	1/676	0/222	1/56
Bronchial hyperactivityRespiratory, thoracic and mediastinal disorders	0/2680	0/676	0/222	1/56
Haemorrhoid operationSurgical and medical procedures	0/2680	0/676	1/222	0/56
AppendicitisInfections and infestations	5/2680	0/676	0/222	0/56
Bacterial infectionInfections and infestations	0/2680	1/676	0/222	0/56
Ligament ruptureInjury, poisoning and procedural complications	0/2680	1/676	0/222	0/56
Bone cystMusculoskeletal and connective tissue disorders	0/2680	1/676	0/222	0/56
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)	1/2680	1/676	0/222	0/56

Most frequent other events

Showing 10 of 16

Most frequent other events
Event	TIV + aH5N1 (18-60 Yrs)	PL + aTIV (18-60 Yrs)	TIV + aH5N1 (>60 Yrs)	PL + aTIV (>60 Yrs)
Injection site painGeneral disorders	1738/2680	459/676	96/222	21/56
MyalgiaMusculoskeletal and connective tissue disorders	1088/2680	296/676	69/222	17/56
Injection site erythemaGeneral disorders	1041/2680	248/676	87/222	18/56
HeadacheNervous system disorders	1031/2680	253/676	54/222	18/56
FatigueGeneral disorders	927/2680	247/676	38/222	9/56
Injection site indurationGeneral disorders	830/2680	195/676	42/222	13/56
Injection site swellingGeneral disorders	632/2680	177/676	28/222	6/56
MalaiseGeneral disorders	542/2680	161/676	33/222	7/56
ChillsGeneral disorders	532/2680	152/676	40/222	13/56
Injection site haemorrahageGeneral disorders	367/2680	111/676	33/222	13/56

Baseline characteristics

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, 2 subjects were changed from TIV + aH5N1 group to PL+ aTIV group). Moreover, a subset to the enrolled population as treated excluded the one subject who was not vaccinated.

Age, Customized
Age, Customized(Years)	TIV + aH5N1	PL+ aTIV	Total
<= 60 years	40.7 ± 11.6	40.5 ± 12.0	40.7 ± 11.7
>60 years	61.9 ± 1.4	62.1 ± 1.8	61.9 ± 1.5

Sex/Gender, Customized
Sex/Gender, Customized(participants)	TIV + aH5N1	PL+ aTIV	Total
Female (<=60 yrs)	1502	388	1890
Male (<=60 yrs)	1190	291	1481
Female (>60 yrs)	109	28	137
Male (>60 yrs)	110	28	138

Study locations

2 sites

Tampere Vaccine Research Clinic (15 sites)
Tampere, 33100, Finland
12 Sites
München, 80799, Germany

References and documents

Publications

Vesikari T, Forsten A, Herbinger KH, Cioppa GD, Beygo J, Borkowski A, Groth N, Bennati M, von Sonnenburg F. Safety and immunogenicity of an MF59((R))-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly. Vaccine. 2012 Feb 8;30(7):1388-96. doi: 10.1016/j.vaccine.2011.12.009. Epub 2011 Dec 20. PubMed 22192847 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 23, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00841763
Lead sponsor: Novartis
Collaborators: Novartis Vaccines
Responsible party: Sponsor
First posted: Feb 11, 2009
Start date: Oct 2008
Primary completion: Apr 2009
Completion: Nov 2009
Results posted: Jan 18, 2013
Last update: Apr 23, 2021

Study contacts

Novartis Vaccines

study director · Novartis Vaccines

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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