Study to Evaluate the Efficacy, Safety and Immunogenicity of Influenza Vaccine in Healthy Subjects (Aged 6 to <72 Months) Versus Control Vaccines
- Conditions
- Influenza, Human
- Interventions
- Biological: Adjuvanted trivalent inactivated subunit influenza vaccineBiological: Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccineBiological: Meningococcal C conjugate vaccine or tick-borne encephalitis vaccine
- Registration Number
- NCT00644059
- Lead Sponsor
- Novartis
- Brief Summary
This study will evaluate the efficacy, safety and immunogenicity of one or two 0.25 mL or 0.5 mL intramuscular injections of an adjuvanted influenza vaccine compared with non-influenza and non-adjuvanted influenza control vaccines in subjects 6 to \<72 months of age.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4902
- Children whose parents/legal guardians have given written informed consent prior to study entry: a) aged 6 to <72 months (Part I and II of the study; influenza seasons 2007/2008 and 2008/2009) b) aged 6 to <36 months (Part III of the study; influenza season 2009/2010)
- In good health as determined by: a) medical history, b) physical examination, c) clinical judgment of the investigator
Exclusion criteria:
- Administration of licensed vaccines (including H1N1sw vaccines) within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study. Routine vaccines, according to local recommendations, or any other vaccines not foreseen in the protocol could be given after the active trial phase (i.e., 21 days after last vaccination) has been concluded.
- Receipt of another investigational vaccine or any investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study, whichever is longer, and participation in another clinical trial during the present study.
- Experience of a severe acute infectious disease in the month prior to study start or experience of a mild acute infection disease in the week prior the study start (untreated common cold is acceptable). The severity of the infectious disease occurred will be based on the investigator's judgment.
- Any severe acute respiratory disease and infection requiring systemic antibiotic or antiviral therapy ongoing or resolved within 2 days prior to study start.
- Experience an axillary temperature equal to or greater than 37.8°C (rectal temperature equal to or greater than 38.3°C) within the 2 days before enrollment.
- Any serious disease in the opinion of the investigator including, for example: a) cancer, b) autoimmune disease (including rheumatoid arthritis under immunosuppressive therapy), c) insulin dependent diabetes mellitus, d) chronic pulmonary disease, asthma under inhalative therapy only is acceptable, e) acute or progressive hepatic disease, f) acute or progressive renal disease.
- Known or suspected impairment/alteration of immune function, for example, resulting from: a) receipt of immunosuppressive therapy (corticosteroid -except topical or inhaled steroids- or cancer chemotherapy), b) receipt of immunostimulants, c) receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 90 days and for the full length of the study, d) high risk for developing an immunocompromising disease (suspected or known HIV infection or HIV-related disease).
- Bleeding diathesis.
- History of hypersensitivity to any component of the study medication or chemically related substances.
- History of any anaphylaxis, serious vaccine reactions, or allergy to eggs, egg products or any other vaccine component.
- Laboratory confirmed influenza disease.
- History of neurological disorder or seizures (febrile seizures allowed).
- Received any influenza vaccine.
- Major surgery planned during the study period.
- Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives, e.g., planned travel or relocation of residence that would interfere with completion of study.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TIV-adj Adjuvanted trivalent inactivated subunit influenza vaccine Adjuvanted trivalent inactivated subunit influenza vaccine Flu-control Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine Non-adjuvanted trivalent inactivated subunit influenza vaccine or non-adjuvanted trivalent inactivated split influenza vaccine Non-flu Control Meningococcal C conjugate vaccine or tick-borne encephalitis vaccine Novartis meningococcal C conjugate vaccine or tick-borne encephalitis vaccine
- Primary Outcome Measures
Name Time Method Number of Subjects (Unprimed) 6 to <36 Months Age With Local and Systemic Reactions After Any Vaccination for All Seasons, Comparison of Adjuvanted Trivalent Influenza Vaccine (aTIV) and Flu Vaccine Control. 7 days post-vaccination Safety was assessed in terms of number of subjects experiencing each of the local and systemic reactions within 7-days after any vaccination for all seasons, comparison of adjuvanted Trivalent influenza vaccine (aTIV) and flu vaccine control.
Percentage of Subjects (Unprimed) Aged 6 to <36 Months With Virus-Confirmed Influenza, Comparison of aTIV and Non-flu Vaccine Control (Men C/TBE Vaccine) 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in 6 to \<36 month unprimed subjects for Absolute Efficacy. This primary endpoint is only for homologous strains.
- Secondary Outcome Measures
Name Time Method Indirect Protective Effect of Fluad (NH Composition 2007/2008), Compared to Non-flu Control and Flu Control, in Connection to Household-contact Persons Via a Questioning of the Parents About ILI of Persons Living in the Same Household as the Study Child 3 weeks after 2nd vaccination Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMTs, in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50 , 181 Immunogenicity was analyzed in terms of Geometric Mean Titers (GMTs) as measured by hemagglutination inhibition (HI) assay. For each strain and each vaccine group, least squares GMTs, associated 2-sided 95% confidence interval were determined for all time points Superiority analysis: GMT-TIV-adj/GMT-Flu-control \>1 and GMT-TIV-adj/GMT-Non Flu-control \>1 should be elicited to show that GMT-TIV-adj is superior to GMT-Flu-control/Non Flu-control.
Percentages of Subjects With Seroconversion and Vaccine Group Differences in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50, 181 HI assay was used for the analysis. Seroconversion is defined as negative pre-vaccination serum (\<10)/ post-vaccination HI titer ≥1:40.
Seroconversion is defined as either pre-vaccination HI titer \<10 and a post-vaccination HI titer ≥1:40 or a prevaccination HI titer ≥10 and a minimum 4-fold rise in post-vaccination HI antibody titer. The lower bound of the two-sided 95% confidence interval (CI) for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40%.Number of Subjects With Local and Systemic Reactions for Egg and Cell Derived Inactivated Novel Swine Origin A/H1N1 Subunit Influenza Vaccines After Each Vaccination for All Seasons 7 days post-vaccination Incidence Rate of the 2009-2010 H1N1 Swine Pandemic Caused by a Novel Influenza A (H1N1) Virus of Swine Origin in Unprimed Children Aged 6 to <36 and 6 to <72 Months 3 weeks after 2nd vaccination Number of Subjects (Unprimed) of 6 to <72 Months Age With Local and Systemic Reactions After Any Vaccination 7 days post-vaccination Safety was assessed as the number of subjects aged 6 to \<72 months who reported solicited local or systemic adverse events after any vaccination with TIV-adj for all seasons.
Number of Subjects (Unprimed) With Unsolicited Adverse Events Reported After Any Vaccination Study day 1 to Study day 181 Number of subjects aged 6 to \<36 months and in the overall age cohort (unprimed children aged 6 to \<72 months) experiencing each of the unsolicited adverse events (AEs) throughout the study
Loss of Days of Usual Activity (Job, School, Day Care, Household/Family/Community Activities) Due to Influenza Like Illness (ILI) in Subjects in Aged 6 to <72 and 6 to <36 Months and in Direct Caregivers Living in the Household. 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine for Influenza like illnesses for seasons 2007/08 and 2008/09.
Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu-vaccine Control (Matched Strains) 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in subjects aged 6 to \<72 months (unprimed) for Absolute Efficacy.
For Relative efficacy, the comparison was made between adjuvanted influenza vaccine (TIV-adj) and flu vaccine control.Percentage of Subjects (Unprimed) Aged 6 to <72 Months With Virus-Confirmed Influenza, Comparison of aTIV to Non-flu Vaccine Control and Flu Vaccine Control (Any Strains). 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses (regardless of antigenic match to those contained in the vaccine) were assessed and compared between the adjuvanted influenza vaccine (TIV-adj) and non-influenza vaccines (Non-flu control) in subjects aged 6 to \<72 months (unprimed) for Absolute Efficacy.
For Relative efficacy, the comparison was made between adjuvanted influenza vaccine (TIV-adj) and flu vaccine control.Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <72 Months for Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50, 181 Hemagglutination Inhibition (HI) assay was used for the analysis. Geometric mean titer ratios (GMRs) of study day 29/study day 1, study day 50/study day 1, study day 181/study day 1 were evaluated.
The criteria for evaluation is GMR \>2.5Percentages of Subjects With HI Titers ≥ 1:40 in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 Homologous and Heterologous Strains On study days 1, 29, 50, 181 Hemagglutination Inhibition (HI) assay was used for the analysis.
Percentage of subjects achieving seroprotection (i.e., with HI titer ≥1:40) at study day 1, study day 29, study day 50 and a study day 181 and associated 95% Confidence Intervals. The lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%.Number of Events of Influenza Like Illness for Combined Seasons 2007/08 and 2008/09. 3 weeks after 2nd vaccination The number of events of Influenza like Illness reported by subjects aged 6 to \<72 months was assessed for combined seasons 2007/08 and 2008/09
Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of GMRs, in Unprimed Subjects Aged 6 to <36 Months or Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50 and 181 The immunogenicity was assessed in terms of Geometric mean titer ratios (GMRs) of study day 29/study day 1, study day 50/study day 1, study day 181/study day 1 were evaluated.
The criteria for evaluation is GMR \>2.5Immunogenicity of aTIV, Compared to Flu and Non-Flu-control, in Terms of Geometric Mean Titers (GMTs), in Unprimed Subjects Aged 6 to <36 Months for Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50 and 181 Immunogenicity was analyzed in terms of Geometric Mean Titers (GMTs) as measured by hemagglutination inhibition (HI) assay. For each strain and each vaccine group, least squares GMTs, associated 2-sided 95% confidence interval were determined for all time points.
Superiority analysis: GMT-TIV-adj/GMT-Flu-control \>1 should be elicited to show that GMT-TIV-adj is superior to GMT-Flu-controlPercentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With HI Titer ≥1:40 in Season 2008/09 HI Assay(Homologous and Heterologous Strains) On study days 1, 29, 50, 181 Percentage of subjects achieving seroprotection (i.e., with HI titer ≥1:40) at study day 1, study day 29, study day 50 and a study day 181 and associated 95% CI. The lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%.
Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With Seroconversion From Baseline, for Season 2008/09 (Homologous and Heterologous Strains) On study days 1, 29, 50, 181 HI assay was used for the analysis. Seroconversion is defined as negative pre-vaccination serum (\<10)/ post-vaccination HI titer ≥1:40.
Seroconversion is defined as either pre-vaccination HI titer \<10 and a post-vaccination HI titer ≥1:40 or a prevaccination HI titer ≥10 and a minimum four-fold rise in post-vaccination HI antibody titer.
The lower bound of the two-sided 95% confidence interval (CI) for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40%.Number of Subjects (Unprimed) With Influenza Like Illnesses (ILIs) in the 6 to <72 Months Age Cohort for Combined Seasons 2007/08 and 2008/09 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine in 6 to \<72 month old subjects for Influenza like illnesses for seasons 2007/08 and 2008/09.
Number of Subjects With Influenza Like Illnesses (ILIs) in the 6 to <36 Months and in Overall Age Cohort (Unprimed Subjects Aged 6 to <72 Months) for Combined Seasons 2007/08 and 2008/09 3 weeks after 2nd vaccination Virus-confirmed influenza illnesses were assessed and trivalent adjuvanted influenza vaccine (TIV-adj) was compared with Non-flu control vaccine and Flu-control vaccine for Influenza like illnesses for seasons 2007/08 and 2008/09.
Trial Locations
- Locations (101)
East Vantaa Clinic
🇫🇮East Vaanta, Finland
Jarvenpaa Vaccine Research Clinic
🇫🇮Jarvenpaa, Finland
Kokkola Vaccine Research Clinic
🇫🇮Kokkola, Finland
Lahti vaccine research Clinic
🇫🇮Lahti, Finland
Kuopio Vaccine Research Clinic
🇫🇮Kuopio, Finland
Tampere Vaccine Research Clinic
🇫🇮Tampere, Finland
Turku Clinic
🇫🇮Turku, Finland
Praxis Dr med Ursula Hornlein
🇩🇪Berlin, Germany
Praxis Dr med Thilo Heising
🇩🇪Aalen Wasseralfingen, Germany
Praxis Dr med Thomas Richter
🇩🇪Berlin, Germany
Praxis Dipl med Andreas Muhmer
🇩🇪Berlin, Germany
Praxis Dr med Mechthild Vocks-Hauck
🇩🇪Berlin, Germany
Praxis Dr med Klaus-Peter Falkowski
🇩🇪Berlin, Germany
Praxis Dr med Eva Brand
🇩🇪Berlin, Germany
Praxis Dr med Petra van Stiphout
🇩🇪Berlin, Germany
Praxis Dr med Dorothea Budde
🇩🇪Berlin, Germany
Praxis Dipl. med. F. Temmler / Dipl. med. D. Wenzel
🇩🇪Berlin, Germany
Praxis Dr. med. Cornelia Busse
🇩🇪Berlin, Germany
Praxis Dr Luise Schroeter
🇩🇪Berlin, Germany
Praxis Dr Norbert Meister
🇩🇪Bindlach, Germany
"Praxis Dr med Dietrich Lasius"
🇩🇪Berlin, Germany
Praxis Dr. med. Petra Sandow
🇩🇪Berlin, Germany
Praxis Dr med Thomas Tuschen
🇩🇪Binngen Rhein, Germany
Praxis Karl-Heinz Blattel
🇩🇪Braunfels, Germany
Praxis Dr. med. Maria R. Holtorf
🇩🇪Brunsbuettel, Germany
Praxis Dr. med. Roland Knecht
🇩🇪Bretten, Germany
Praxis Dr Klaus Helm
🇩🇪Detmold, Germany
Praxis Joseph Zakarian
🇩🇪Duesseldorf, Germany
Praxis Dr. med. Dirk Straub
🇩🇪Essen, Germany
Praxis Dr med Hans-Henning Peters
🇩🇪Eschwege, Germany
Praxis Dr med Hans-Joachim Buttner
🇩🇪Gau-Odernheim, Germany
Praxis Dr med Rainer Haase
🇩🇪Flensburg, Germany
Praxis Dr Lothar MaurerJun
🇩🇪Frankenthal, Germany
Praxis Dr. med. Per Gildberg
🇩🇪Flensburg, Germany
Peaxis Dr H Outzen jun
🇩🇪Flensburg, Germany
Praxis Dr med Walter Otto
🇩🇪Fulda, Germany
Praxis Dr med Christian Kayser
🇩🇪Gehrden, Germany
Praxis Ute Jessat
🇩🇪Gluecksburg, Germany
Praxis Dr. med. Dubravka Pock-Lutz
🇩🇪Grevenbroich, Germany
Praxis Dr. med. Malte Klarczyk
🇩🇪Hamburg, Germany
Praxis Dr Anna Halat
🇩🇪Hamburg, Germany
Praxid Dr. med. Karl-Heinrich Hansen
🇩🇪Hamburg, Germany
Praxis Dr med Jurgen Schwalbe
🇩🇪Hameln, Germany
Praxis Dr med Hans-Heinrich Rohe
🇩🇪Hille, Germany
Praxis Dr Marlies Bolich
🇩🇪Jena, Germany
Praxis Dr med Bernard Nast
🇩🇪Hamburg, Germany
Praxis Peter Bosch
🇩🇪Karlsruhe-Oberreut, Germany
Praxis Dr Peter Andoko Soemantri
🇩🇪Kleve-Materborn, Germany
Praxis Dr. Michael Muehlschlegel
🇩🇪Lauffen, Germany
Praxis Dr Sibylle Hetzinger
🇩🇪Lobenstein, Germany
Praxis Dipl med Dagmar Manegold-Randel
🇩🇪Lohne, Germany
Praxis Dr. Renate Lang
🇩🇪Ludwigsburg, Germany
Praxis Dr med Julika Kelber
🇩🇪Luneburg, Germany
Praxis Uwe Jakob
🇩🇪Mainz, Germany
Johannes Gutenberg-University
🇩🇪Mainz, Germany
Praxis Dr med Volker Tempel
🇩🇪Marbach a. N., Germany
Praxis Dr med Falko Panzer
🇩🇪Mannheim, Germany
Praxis Ralph Koellges
🇩🇪Moenchengladbach, Germany
Praxis Dr. med. Herbert Kollaschinski
🇩🇪Marktredwitz, Germany
Praxis Dr med Matthias Donner
🇩🇪Moenchengladbach, Germany
Praxis Dr. med. Janina Joiko
🇩🇪Muenchen, Germany
"Praxis Prof Dr med Stefan Walter Eber"
🇩🇪Munchen, Germany
Praxis Dr med Peter Dietl
🇩🇪Munchen, Germany
Praxis Dr med Hartmut Scheele
🇩🇪Niedernhausen, Germany
Praxis Dipl Med Ute Macholdt
🇩🇪Neuhaus am Rennweg, Germany
Praxis Dr. med. S. Mohns-Petersen
🇩🇪Niebuell, Germany
Praxis Dr Sabine Maruschke
🇩🇪Neumuenster, Germany
Praxis Drs J und K Kandzora
🇩🇪Neumuenster, Germany
Praxis Zlatka Zochev Donkov
🇩🇪Rendsburg, Germany
Praxis Dr med Stefan Noll
🇩🇪Porta Westfalica, Germany
Praxis Dr med Michael Vomstein
🇩🇪Schwabisch Hall, Germany
"Praxis Dr med Gunther Knapp"
🇩🇪Schwieberdingen, Germany
Praxis Dr Ulrich Pfletschinger
🇩🇪Stuttgart, Germany
Praxis Dr med Ulrich Soergel
🇩🇪Stadthagen, Germany
Praxis Thomas Morandini
🇩🇪Schönenberg, Germany
Praxis Dr. med Heidi B. John-Wagenmann
🇩🇪Stuttgart, Germany
Praxis Dr. med. Rolf Ebert
🇩🇪Tauberbischofsheim, Germany
Praxis Dr med Steffi Bulst
🇩🇪Wurzen, Germany
Praxis Dr. med Manfred Heitz
🇩🇪Stuttgart, Germany
Praxis Dr med Karl-Eugen Mai
🇩🇪Tettnang, Germany
Praxis Dr med Ralph Maier
🇩🇪Tuttlingen, Germany
Praxis Dr Per Bergmann
🇩🇪Winsen, Germany
Praxis Dr med Klaus Kindler
🇩🇪Trier, Germany
Praxis Dr med Ulrich Umpfenbach
🇩🇪Viersen, Germany
Ospedale Maggiore della Carita
🇮🇹Novara, Italy
Praxis Dr med Volker Kemmerich
🇩🇪Weinstadt, Germany
Fondazione IRCCS Policlinico Mangiagalli e Regina Elena
🇮🇹Milano, Italy
Praxis Dr med Philip Fellner von Feldegg
🇩🇪Munster / NRW, Germany
Praxis Dr Rossius
🇩🇪Neumuenster, Germany
Praxis Dr. Elmar Dietmair
🇩🇪Bobingen, Germany
Praxis Dr med Brigitta Becker
🇩🇪Bochum, Germany
Espoo Vaccine Research Clinic
🇫🇮Espoo, Finland
Kotka Clinic
🇫🇮Kotka, Finland
West Vantaa Clinic
🇫🇮West Vantaa, Finland
Kuopio Vaccine Clinic
🇫🇮Kuopio, Finland
Oulu Vaccine Research Clini
🇫🇮Oulu, Finland
Vantaa West Vaccine Research Clinic
🇫🇮Vantaa, Finland
Helsinki South Vaccine Research Clinic
🇫🇮Helsinki, Finland
Helsinki East Vaccine Research Clinic
🇫🇮Helsinki, Finland
Pori Vaccine Research Clinic
🇫🇮Pori, Finland
Seinajoki Clinic
🇫🇮Seinajoki, Finland