Clinical trial NCT00644059: Study to Evaluate the Efficacy, Safety and Immunogenicity of Influenza Vaccine in Healthy Subjects (Aged 6 to <72 Months) Versus Control Vaccines
Official title: A Phase III, Randomized, Observer-blind, Controlled, Multi-center Clinical Trial to Evaluate the Efficacy, Safety and Immunogenicity of One and Two Intramuscular Doses of Influenza Vaccine Versus Control Vaccines in Healthy Subject Aged 6 to <72 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza, Human
Keywords: Influenza
vaccine
children
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2008-03-26
Enrollment: 4902
Sex: ALL
Minimum age (years): 6
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Primary outcomes:
measure: 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.
timeFrame: 7 days post-vaccination
measure: 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)
timeFrame: 3 weeks after 2nd vaccination
Secondary outcomes:
measure: Number of Subjects (Unprimed) of 6 to <72 Months Age With Local and Systemic Reactions After Any Vaccination
timeFrame: 7 days post-vaccination
measure: Number of Subjects (Unprimed) With Unsolicited Adverse Events Reported After Any Vaccination
timeFrame: Study day 1 to Study day 181
measure: 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)
timeFrame: 3 weeks after 2nd vaccination
measure: 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).
timeFrame: 3 weeks after 2nd vaccination
measure: 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
timeFrame: 3 weeks after 2nd vaccination
measure: 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
timeFrame: 3 weeks after 2nd vaccination
measure: 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.
timeFrame: 3 weeks after 2nd vaccination
measure: Number of Events of Influenza Like Illness for Combined Seasons 2007/08 and 2008/09.
timeFrame: 3 weeks after 2nd vaccination
measure: 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)
timeFrame: On study days 1, 29, 50 and 181
measure: Immunogenicity 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)
timeFrame: On study days 1, 29, 50 and 181
measure: Percentage (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)
timeFrame: On study days 1, 29, 50, 181
measure: Percentage (95% CI) of Unprimed Subjects Aged 6 to <36 Months With Seroconversion From Baseline, for Season 2008/09 (Homologous and Heterologous Strains)
timeFrame: On study days 1, 29, 50, 181
measure: 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)
timeFrame: On study days 1, 29, 50 , 181
measure: 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)
timeFrame: On study days 1, 29, 50, 181
measure: Percentages of Subjects With HI Titers ≥ 1:40 in Unprimed Subjects 6 to <72 Months of Age for Season 2008/09 Homologous and Heterologous Strains
timeFrame: On study days 1, 29, 50, 181
measure: 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)
timeFrame: On study days 1, 29, 50, 181
measure: 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
timeFrame: 7 days post-vaccination
measure: 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
timeFrame: 3 weeks after 2nd vaccination
measure: 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
timeFrame: 3 weeks after 2nd vaccination
Other outcomes:
Locations:
city: East Vaanta
country: Finland
facility: East Vantaa Clinic
city: Espoo
country: Finland
facility: Espoo Vaccine Research Clinic
city: Helsinki
country: Finland
facility: Helsinki South Vaccine Research Clinic
city: Helsinki
country: Finland
facility: Helsinki East Vaccine Research Clinic
city: Jarvenpaa
country: Finland
facility: Jarvenpaa Vaccine Research Clinic
city: Kokkola
country: Finland
facility: Kokkola Vaccine Research Clinic
city: Kotka
country: Finland
facility: Kotka Clinic
city: Kuopio
country: Finland
facility: Kuopio Vaccine Clinic
city: Kuopio
country: Finland
facility: Kuopio Vaccine Research Clinic
city: Lahti
country: Finland
facility: Lahti vaccine research Clinic
city: Oulu
country: Finland
facility: Oulu Vaccine Research Clini
city: Pori
country: Finland
facility: Pori Vaccine Research Clinic
city: Seinajoki
country: Finland
facility: Seinajoki Clinic
city: Tampere
country: Finland
facility: Tampere Vaccine Research Clinic
city: Turku
country: Finland
facility: Turku Clinic
city: Vantaa
country: Finland
facility: Vantaa West Vaccine Research Clinic
city: West Vantaa
country: Finland
facility: West Vantaa Clinic
city: Aalen Wasseralfingen
country: Germany
facility: Praxis Dr med Thilo Heising
city: Berlin
country: Germany
facility: Praxis Dr med Ursula Hornlein
city: Berlin
country: Germany
facility: Praxis Dr med Thomas Richter
city: Berlin
country: Germany
facility: Praxis Dipl med Andreas Muhmer
city: Berlin
country: Germany
facility: Praxis Dr med Mechthild Vocks-Hauck
city: Berlin
country: Germany
facility: Praxis Dr med Klaus-Peter Falkowski
city: Berlin
country: Germany
facility: Praxis Dr med Eva Brand
city: Berlin
country: Germany
facility: Praxis Dr med Dorothea Budde
city: Berlin
country: Germany
facility: Praxis Dr. med. Cornelia Busse
city: Berlin
country: Germany
facility: Praxis Dipl. med. F. Temmler / Dipl. med. D. Wenzel
city: Berlin
country: Germany
facility: Praxis Dr med Petra van Stiphout
city: Berlin
country: Germany
facility: Praxis Dr Luise Schroeter
city: Berlin
country: Germany
facility: "Praxis Dr med Dietrich Lasius"
city: Berlin
country: Germany
facility: Praxis Dr. med. Petra Sandow
city: Bindlach
country: Germany
facility: Praxis Dr Norbert Meister
city: Binngen Rhein
country: Germany
facility: Praxis Dr med Thomas Tuschen
city: Bobingen
country: Germany
facility: Praxis Dr. Elmar Dietmair
city: Bochum
country: Germany
facility: Praxis Dr med Brigitta Becker
city: Braunfels
country: Germany
facility: Praxis Karl-Heinz Blattel
city: Bretten
country: Germany
facility: Praxis Dr. med. Roland Knecht
city: Brunsbuettel
country: Germany
facility: Praxis Dr. med. Maria R. Holtorf
city: Detmold
country: Germany
facility: Praxis Dr Klaus Helm
city: Duesseldorf
country: Germany
facility: Praxis Joseph Zakarian
city: Eschwege
country: Germany
facility: Praxis Dr med Hans-Henning Peters
city: Essen
country: Germany
facility: Praxis Dr. med. Dirk Straub
city: Flensburg
country: Germany
facility: Praxis Dr med Rainer Haase
city: Flensburg
country: Germany
facility: Praxis Dr. med. Per Gildberg
city: Flensburg
country: Germany
facility: Peaxis Dr H Outzen jun
city: Frankenthal
country: Germany
facility: Praxis Dr Lothar MaurerJun
city: Fulda
country: Germany
facility: Praxis Dr med Walter Otto
city: Gau-Odernheim
country: Germany
facility: Praxis Dr med Hans-Joachim Buttner
city: Gehrden
country: Germany
facility: Praxis Dr med Christian Kayser
city: Gluecksburg
country: Germany
facility: Praxis Ute Jessat
city: Grevenbroich
country: Germany
facility: Praxis Dr. med. Dubravka Pock-Lutz
city: Hamburg
country: Germany
facility: Praxis Dr. med. Malte Klarczyk
city: Hamburg
country: Germany
facility: Praxid Dr. med. Karl-Heinrich Hansen
city: Hamburg
country: Germany
facility: Praxis Dr Anna Halat
city: Hamburg
country: Germany
facility: Praxis Dr med Bernard Nast
city: Hameln
country: Germany
facility: Praxis Dr med Jurgen Schwalbe
city: Hille
country: Germany
facility: Praxis Dr med Hans-Heinrich Rohe
city: Jena
country: Germany
facility: Praxis Dr Marlies Bolich
city: Karlsruhe-Oberreut
country: Germany
facility: Praxis Peter Bosch
city: Kleve-Materborn
country: Germany
facility: Praxis Dr Peter Andoko Soemantri
city: Lauffen
country: Germany
facility: Praxis Dr. Michael Muehlschlegel
city: Lobenstein
country: Germany
facility: Praxis Dr Sibylle Hetzinger
city: Lohne
country: Germany
facility: Praxis Dipl med Dagmar Manegold-Randel
city: Ludwigsburg
country: Germany
facility: Praxis Dr. Renate Lang
city: Luneburg
country: Germany
facility: Praxis Dr med Julika Kelber
city: Mainz
country: Germany
facility: Johannes Gutenberg-University
city: Mainz
country: Germany
facility: Praxis Uwe Jakob
city: Mannheim
country: Germany
facility: Praxis Dr med Falko Panzer
city: Marbach a. N.
country: Germany
facility: Praxis Dr med Volker Tempel
city: Marktredwitz
country: Germany
facility: Praxis Dr. med. Herbert Kollaschinski
city: Moenchengladbach
country: Germany
facility: Praxis Dr med Matthias Donner
city: Moenchengladbach
country: Germany
facility: Praxis Ralph Koellges
city: Muenchen
country: Germany
facility: Praxis Dr. med. Janina Joiko
city: Munchen
country: Germany
facility: "Praxis Prof Dr med Stefan Walter Eber"
city: Munchen
country: Germany
facility: Praxis Dr med Peter Dietl
city: Munster / NRW
country: Germany
facility: Praxis Dr med Philip Fellner von Feldegg
city: Neuhaus am Rennweg
country: Germany
facility: Praxis Dipl Med Ute Macholdt
city: Neumuenster
country: Germany
facility: Praxis Dr Rossius
city: Neumuenster
country: Germany
facility: Praxis Dr Sabine Maruschke
city: Neumuenster
country: Germany
facility: Praxis Drs J und K Kandzora
city: Niebuell
country: Germany
facility: Praxis Dr. med. S. Mohns-Petersen
city: Niedernhausen
country: Germany
facility: Praxis Dr med Hartmut Scheele
city: Porta Westfalica
country: Germany
facility: Praxis Dr med Stefan Noll
city: Rendsburg
country: Germany
facility: Praxis Zlatka Zochev Donkov
city: Schwabisch Hall
country: Germany
facility: Praxis Dr med Michael Vomstein
city: Schwieberdingen
country: Germany
facility: "Praxis Dr med Gunther Knapp"
city: Schönenberg
country: Germany
facility: Praxis Thomas Morandini
city: Stadthagen
country: Germany
facility: Praxis Dr med Ulrich Soergel
city: Stuttgart
country: Germany
facility: Praxis Dr Ulrich Pfletschinger
city: Stuttgart
country: Germany
facility: Praxis Dr. med Manfred Heitz
city: Stuttgart
country: Germany
facility: Praxis Dr. med Heidi B. John-Wagenmann
city: Tauberbischofsheim
country: Germany
facility: Praxis Dr. med. Rolf Ebert
city: Tettnang
country: Germany
facility: Praxis Dr med Karl-Eugen Mai
city: Trier
country: Germany
facility: Praxis Dr med Klaus Kindler
city: Tuttlingen
country: Germany
facility: Praxis Dr med Ralph Maier
city: Viersen
country: Germany
facility: Praxis Dr med Ulrich Umpfenbach
city: Weinstadt
country: Germany
facility: Praxis Dr med Volker Kemmerich
city: Winsen
country: Germany
facility: Praxis Dr Per Bergmann
city: Wurzen
country: Germany
facility: Praxis Dr med Steffi Bulst
city: Milano
country: Italy
facility: Fondazione IRCCS Policlinico Mangiagalli e Regina Elena
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita
Study officials:
affiliation: Novartis
name: Novartis Vacccines and Diagnostics
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Knuf M, Wutzler P, Karvonen A, Kieninger-Baum D, Schmitt HJ, Baehner F, Borkowski A, Tsai TF, Clemens R. Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med. 2011 Oct 13;365(15):1406-16. doi: 10.1056/NEJMoa1010331.