InfluenzaPhase 2/3NCT00645411

Pediatric Safety and Immunogenicity Study of Cell-Culture Derived and Egg-based Subunit Influenza Vaccines in Healthy Children and Adolescents

A Phase 2/3 study testing Cell culture-derived influenza subunit vaccine (cTIV) and Egg derived influenza subunit vaccine (eTIV) in people with Influenza, run by Novartis at 60 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 3 to 17 yearsHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: Cell culture-derived influenza subunit vaccine (cTIV) and Egg derived influenza subunit vaccine (eTIV)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3,604 participants
Where: 60 sitesin 7 countries
Study dates: Oct 2007to Jul 2008
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 17 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Subjects aged 9 to 17 years (Cohorts 1 and 2) and 3 to 8 years (Cohort 3), whose parents/legal guardians have given written informed consent prior to study entry. Assent will be obtained from subjects according to age requirements of the ECs/IRBs;
In good health as determined by:
medical history,
physical examination,
clinical judgment of the Investigator;
Able to comply with all study procedures and available for all clinic visits and telephone calls scheduled in the study.

Who cannot join

Any serious disease, such as:
cancer,
autoimmune disease (including rheumatoid arthritis),
diabetes mellitus,
chronic pulmonary disease,
acute or progressive hepatic disease,

Show all 27Show fewer

acute or progressive renal disease;
History of any anaphylaxis or serious reaction following administration of vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials;
Known or suspected impairment/alteration of immune function, including:
use of immunosuppressive therapy such as systemic corticosteroids known to be associated with the suppression of hypothalamic-pituitary-adrenal (HPA) axis or chronic use of inhaled high-potency corticosteroids within 60 days prior to Visit 1,
cancer chemotherapy,
receipt of immunostimulants within 60 days prior to Visit 1,
receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study,
known HIV infection or HIV-related disease;
History of Guillain-Barré syndrome;
Bleeding diathesis;
Surgery planned during the study period;
Receipt of another investigational agent within 90 days, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another clinical study through the end of the study;
Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1;
Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
For subjects aged 3 to 8 years old, ever received two doses of an influenza vaccine in one influenza season;
Receipt of an influenza vaccine within 6 months prior to Visit 1;
Experienced a temperature 38.0°C [100.4°F]) and/or any acute illness within 3 days prior to Visit 1;
Pregnant or nursing mother;
Female of childbearing potential who is sexually active and has not used acceptable birth control measures for at least 2 months prior to study entry and who does not plan to use acceptable birth control measures during the 3 weeks following vaccination or refuses to have a urine pregnancy test prior to enrollment. Oral, injected, inserted or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device are considered acceptable forms of birth control;
Children of research staff or those living with research staff directly involved with the clinical study. Research staff are individuals with direct study subject contact, indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.;
Any condition, which in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

Trial locations and contacts

60 sites in 7 countries.

Country

City, postcode or hospital

60 sites in 7 countries

United States16 sites

Site 02
Bardstown, Kentucky, 40004
Site 08
Bountiful, Utah, 84010
Site 06
Burke, Virginia, 22105
Site 10
Downey, California, 90241
Site 04
Edison, New Jersey, 08817
Site 05
Endwell, New York, 13760
Site 09
Fayetteville, Arkansas, 72703
Site 16
Fort Worth, Texas, 76135
Site 14
Metairie, Louisiana, 70006
Site 11
Omaha, Nebraska, 68134
Site 07
Salt Lake City, Utah, 84109
Site 03
Salt Lake City, Utah, 84121
Site 13
San Angelo, Texas, 76904
Site 12
San Antonio, Texas, 78205
Site 15
Spokane, Washington, 99202
Site 01
St Louis, Missouri, 63104

Other trials in United States

Finland14 sites

Site 70: Espoon rokotetutkimusklinikka
Heikintori, Espoo, 02100
Site 71: Etelä-Helsingin rokotetutkimusklinikka
Helsinki, Helsinki, 00100
Site 72: Itä-Helsingin rokotetutkimusklinikka
Helsinki, Helsinki, 00930
Site 76: Järvenpään rokotetutkimusklinikka
Jarvenpaa, Järvenpää, 04400
Site 77: Kotkan rokotetutkimusklinikka
Kotka, Kotka, 48600
Site 67: Lahden rokotetutkimusklinikka
Lahti, Lahti, 15140
Site 78: Kuopio Vaccine Research Clinic
Microkatu 1,Osa/Section A, 3rd Floor Pl1188, Kuopio, 70211
Site 75: Oulun rokotetutkimusklinikka
Oulu, Oulu, 90100
Site 68: Porin rokotetutkimusklinikka
Pori, Pori, 28120
Site 79: Kokkola Vaccine Research Clinic
Rantakatu 7, Kokkola, 67100
Site 66: Tampereen rokotetutkimusklinikka
Tampere, Pirkanmaa, 33100
Site 69: Turun rokotetutkimusklinikka
Turku, Turku, 20520
Site 73: Itä-Vantaan rokotetutkimusklinikka
Vantaa, Vantaa, 01300
Site 74: Länsi-Vantaan rokotetutkimusklinikka
Vantaa, Vantaa, 01600

Other trials in Finland

Croatia9 sites

Site 44:Spec. Pediatric Dispensary
Đakovo, Dakovo
Site 83
Ljudevita Gaja 2, Djakovo
Site 43: Spec. Pediatric Dispensary
Sisak, Sisak
Site 27:Institute of Public Health
Zagreb, City of Zagreb
Site 29: Institute of Public Health
Zagreb, City of Zagreb
Site 40:Spec. Pediatric Dispensary
Zagreb, City of Zagreb
Site 49: Spec. Pediatric Dispensary
Zagreb, City of Zagreb
Site 50: Spec. Pediatric Dispensary
Zagreb, City of Zagreb
Site 86: Spec. Pediatric Dispensary
Zagreb, City of Zagreb

Other trials in Croatia

Hungary8 sites

Site 57: Házi Gyermekorvosi Rendelő
Budapest, Budapest, 1042
Site 53: Heim Pál Gyermekkórház
Budapest, Budapest, 1089
Site 52: Ferencvárosi Gyermekorvos Kft.
Budapest, Budapest, 1097
Site 56: Házi Gyermekorvosi Rendelő
Budapest, Budapest, 1136
Site 54: Házi Gyermekorvosi Rendelő
Budapest, Budapest, 1173
Site 51: 5053. számú Gyermekorvosi Rendelő
Miskolc, Miskolc, 3534
Site 55: Revamed kft.
Nyíregyháza, Nyíregyháza, 4481
Site 59: Vas Megyei Markusovszky Lajos, Általános, Rehabilitációs és Gyógyfürdő Kórház, Egyetemi Oktató Kórház
Szombathely, Szombathely, 9700

Other trials in Hungary

Lithuania6 sites

Site 35
Kaunas, Kaunas County, 48259
Site 36
Vilnius, Vilnius County, 01117
Site 32
Vilnius, Vilnius County, 02169
Site 34
Vilnius, Vilnius County, 04318
Site 31
Vilnius, Vilnius County, 10207
Site 33
Vilnius, Vilnius County, 11200

Other trials in Lithuania

Italy5 sites

Site 42: Dipartimento di Medicina Clinica e Sperimentale - Sezione di Igiene e Medicina Preventiva
Ferrara, Ferrara, 44100
Site 47: Dipartimento Scienze della Salute, Sezione di Igiene e Medicina Preventiva, Univesità di Genova
Genova, Genova, 16132
Site 41: Ospedale Maggiore della Carità-Clinica Pediatrica
Novara, Novara, 28100
Site 46: USL 2 Perugia, Distretto del perugino, Centro di Salute n. 4 (Madonna Alta) e n. 6 (Ellera di Corciano del distretto del perugino)
Perugia, Perugia, 06070
Site 45: AUSL 7
Ragusa, Ragusa, 97100

Other trials in Italy

Romania2 sites

Site 25
Campulung Muscel, Argeş, 115100
Site 21
Craiova, Dolj, 200642

Other trials in Romania

About this study

Official title: A Combined Phase II/III, Observer-Blind, Randomized, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs, in Healthy Children and Adolescents

The present study is the first study designed to evaluate safety, tolerability and immunogenicity of the cell culture-derived influenza vaccine in healthy children and adolescents aged 3 to 17 years. A step-down approach is utilized in which reactogenicity and safety will be assessed in children and adolescents 9 to 17 years of age (Cohort 1) prior to enrolling additional children and adolescents 9 to 17 years of age (Cohort 2) and children 3 to 8 years of age (Cohort 3).

Conditions: Influenza
Being tested: Cell culture-derived influenza subunit vaccine (cTIV), Egg derived influenza subunit vaccine (eTIV)
Keywords: Influenza, Flu, Cell Culture-Derived, Egg-Derived, Healthy Children, Healthy Adolescents, Safety, Immunogenicity, Trivalent, Inactivated, Vaccination
Medical subject headings: Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cell culture-derived influenza subunit vaccine (cTIV)Biological
One 0.5 ml injection of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
Egg derived influenza subunit vaccine (eTIV)Biological
One 0.5 ml injection of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.
Cell culture-derived influenza subunit vaccine (cTIV)Biological
Two 0.5 mL injections,of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm, administered four weeks apart.
Egg derived influenza subunit vaccine (eTIV)Biological
Two 0.5 mL injections of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm,administered four weeks apart.

Study groups in NCT00645411
Study group	Role	What they receive
Cohorts 1 + Cohort 2 (9-17 Yrs) cTIV	Experimental	All subjects received one 0.5 mL IM injection, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like, and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere Receives: Biological: Cell culture-derived influenza subunit vaccine (cTIV)
Cohorts 1 + Cohort 2 (9-17 Yrs) eTIV	Active comparator	All subjects received one 0.5 mL injection, of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere. Receives: Biological: Egg derived influenza subunit vaccine (eTIV)
Cohort 3 (3-8 Yrs) cTIV	Experimental	All subjects received two 0.5 mL injections, administered four weeks apart, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere Receives: Biological: Cell culture-derived influenza subunit vaccine (cTIV)
Cohort 3 (3-8 Yrs) eTIV	Active comparator	All subjects received two 0.5 mL injections, administered four weeks apart of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere Receives: Biological: Egg derived influenza subunit vaccine (eTIV)

What is being measured

The primary outcome is the main question the study is designed to answer.

Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age.
GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.
Measured: Day 50 post vaccination
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
To demonstrate non-inferiority of the cell culture-derived influenza (cTIV) vaccine to the egg-derived (eTIV) influenza vaccine in the percentage of subjects achieving seroconversion or significant increase in antibody titer post vaccination, for all three strains, after two injections administered four weeks apart in children 3 to 8 years of age.
Seroconversion rate was evaluated using two assays- HI egg derived antigen assay and HI cell derived antigen assay.
Measured: Day 50 post vaccination

Secondary outcomes (10)

Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 9 to 17 years of age after one injection of either cTIV vaccine or eTIV.
GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.
Measured: Day 29 post vaccination
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.
Immunogenicity was evaluated in terms of Geometric Mean Ratio (GMRs) in 9 to 17 year-old children and adolescents after one injection of either cTIV vaccine or eTIV.
The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (day29/day1) in HI antibody titer is >2.5.
Measured: Day 29 post vaccination
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
To evaluate immunogenicity in terms of percentage of 9 to 17 year-old children and adolescents achieving HI titers ≥40, after one injection of either the cTIV vaccine or the eTIV vaccine.
This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.
Measured: Day 29 post vaccination
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%.
According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.
Measured: Day 29 post vaccination
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children
To evaluate immunogenicity in terms of Geometric Mean Titers (GMTs) in children 3 to 8 years of age after two doses of either cTIV vaccine or eTIV,administered 4 weeks apart.
Measured: Day 29 and Day 50 post vaccination
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children
To evaluate immunogenicity in terms of Geometric Mean Ratio (GMR) in children 3 to 8 years of age after two doses of either the cTIV vaccine or the eTIV vaccine, administered 4 weeks apart according to the CHMP criteria.
The criterion is met according to the European (CHMP) guideline if the mean geometric increase (GMR day 29/day 1 and GMR day 50/day 1) in HI antibody titer is >2.5
Measured: Day 29 and Day 50 post vaccination
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children
To evaluate immunogenicity in terms of HI titers ≥40, in children 3-8 years of age after two doses of either cTIV vaccine or eTIV vaccine, administered 4 weeks apart.
The criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is >70% and according to the US (CBER) guideline if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%.
Measured: Day 29 and Day 50 post vaccination
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children
Seroconversion or significant increase as per CHMP criteria is defined as percentage of subjects with a pre vaccination HI titer <10 to a post vaccination titer ≥40 or a pre vaccination HI titer ≥10 and a ≥4-fold increase in post vaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion or significant increase should be >40%.
According to the CBER criteria, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion/significant increase should be ≥40%.
Measured: Day 29 and Day 50 post vaccination
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.
To evaluate safety and tolerability in terms of number of 9 to 17 year-old children and adolescents (cohorts 1 and 2) reporting local and systemic reactions following of one injection of the cTIV or the eTIV vaccine .
Measured: up to 7 days after vaccination
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children.
To evaluate the safety and tolerability of the cTIV and the eTIV influenza vaccines in 3 to 8 year-old children terms of number of participants reporting local and systemic reactions after each vaccination.
Measured: up to 7 days after each vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2007Jul 2008

First posted27 Mar 2008 (estimated)
Study startOct 2007
Primary completionFeb 2008
Study completionJul 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for InfluenzaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 3,604 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00645411
Sponsor's protocol ID: V58P12
Other IDs: Eudract Number: 2007-001534-13
Status last verified: Oct 2015
First submitted: 21 Mar 2008
Last updated: 23 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Vesikari T, Block SL, Guerra F, Lattanzi M, Holmes S, Izu A, Gaitatzis N, Hilbert AK, Groth N. Immunogenicity, safety and reactogenicity of a mammalian cell-culture-derived influenza vaccine in healthy children and adolescents three to seventeen years of age. Pediatr Infect Dis J. 2012 May;31(5):494-500. doi: 10.1097/INF.0b013e31824bb179.
PubMed 22301476

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
COVID-19 Booster and IIV Schedule in Immunocompromised Hosts
COVID 19, Influenza
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
Recruiting
Light-based Immunomodulation for Guarding Against Human Respiratory Tract Infections
COVID-19 Respiratory Infection, Influenza
Not yet recruiting
Family Physician Nudges for Influenza Vaccination Among Older Adults
Influenza Vaccination
Not yet recruitingPhase 2/3
Evaluation of the Efficacy and Safety of 102D-6 in the Treatment of Acute Uncomplicated Influenza
Influenza, Human

All Influenza trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Combined Phase II/III, Observer-Blind, Randomized, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs, in Healthy Children and Adolescents
ClinicalTrials.gov ID: NCT00645411
Acronym / sponsor ID: V58P12
Conditions: Influenza
Keywords: Influenza, Flu, Cell Culture-Derived, Egg-Derived, Healthy Children, Healthy Adolescents, Safety, Immunogenicity
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,604 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Collaborators: Novartis Vaccines
Study start: Oct 2007
Primary completion: Feb 2008 (actual)
Study completion: Jul 2008 (actual)
First posted: 27 Mar 2008 (estimated)
Results: Posted 16 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 4

Arm	Type	Receives
Cohorts 1 + Cohort 2 (9-17 Yrs) cTIV	Experimental	Biological: Cell culture-derived influenza subunit vaccine (cTIV)All subjects received one 0.5 mL IM injection, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like, and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere
Cohorts 1 + Cohort 2 (9-17 Yrs) eTIV	Active comparator	Biological: Egg derived influenza subunit vaccine (eTIV)All subjects received one 0.5 mL injection, of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere.
Cohort 3 (3-8 Yrs) cTIV	Experimental	Biological: Cell culture-derived influenza subunit vaccine (cTIV)All subjects received two 0.5 mL injections, administered four weeks apart, of cell culture-derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere
Cohort 3 (3-8 Yrs) eTIV	Active comparator	Biological: Egg derived influenza subunit vaccine (eTIV)All subjects received two 0.5 mL injections, administered four weeks apart of egg -derived trivalent influenza vaccine containing 15μg of HA for each strain (A/Solomon Islands/3/2006 [H1N1]-like, A/Wisconsin/67/2005 [H3N2]-like and B/Malaysia/ 2506/2004-like), recommended for the 2007-2008 influenza season in the Northern Hemisphere

Who may qualify

Ages: 3 to 17 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (6 listed)

Subjects aged 9 to 17 years (Cohorts 1 and 2) and 3 to 8 years (Cohort 3), whose parents/legal guardians have given written informed consent prior to study entry. Assent will be obtained from subjects according to age requirements of the ECs/IRBs;
In good health as determined by:
Able to comply with all study procedures and available for all clinic visits and telephone calls scheduled in the study.

Key exclusion criteria (27 listed)

Any serious disease, such as:
History of any anaphylaxis or serious reaction following administration of vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials;
Known or suspected impairment/alteration of immune function, including:
History of Guillain-Barré syndrome;
Bleeding diathesis;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cell culture-derived influenza subunit vaccine (cTIV)One 0.5 ml injection of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.	Biological	Cohorts 1 + Cohort 2 (9-17 Yrs) cTIV
Egg derived influenza subunit vaccine (eTIV)One 0.5 ml injection of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm.	Biological	Cohorts 1 + Cohort 2 (9-17 Yrs) eTIV
Cell culture-derived influenza subunit vaccine (cTIV)Two 0.5 mL injections,of the cell culture-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm, administered four weeks apart.	Biological	Cohort 3 (3-8 Yrs) cTIV
Egg derived influenza subunit vaccine (eTIV)Two 0.5 mL injections of the conventional egg-derived influenza vaccine in the deltoid muscle, preferably of the nondominant arm,administered four weeks apart.	Biological	Cohort 3 (3-8 Yrs) eTIV

Primary outcome

Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
Time frame: Day 50 post vaccination
To demonstrate non-inferiority of the post vaccination hemagglutination inhibition (HI) geometric mean titer (GMT) of the cell culture-derived influenza (cTIV) vaccine to the corresponding GMT of the egg-derived (eTIV) influenza vaccine, for all three strains, after two injections administered four weeks apart to a subset of children 3 to 8 years of age. GMTs were evaluated using two assays, HI egg derived antigen assay and HI cell derived antigen assay.
Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children
Time frame: Day 50 post vaccination
To demonstrate non-inferiority of the cell culture-derived influenza (cTIV) vaccine to the egg-derived (eTIV) influenza vaccine in the percentage of subjects achieving seroconversion or significant increase in antibody titer post vaccination, for all three strains, after two injections administered four weeks apart in children 3 to 8 years of age. Seroconversion rate was evaluated using two assays- HI egg derived antigen assay and HI cell derived antigen assay.

10 secondary outcomes

Geometric Mean Titers After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
Time frame: Day 29 post vaccination
Geometric Mean Ratio After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.
Time frame: Day 29 post vaccination
Percentages of Subjects Who Achieved HI Titers ≥40 After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
Time frame: Day 29 post vaccination
Percentages of Subjects Who Attained Seroconversion or Significant Increase After 1 Dose of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents
Time frame: Day 29 post vaccination
Geometric Mean Titers After Two Doses of the Cell Derived or the Egg Derived Vaccine in 3 to 8 Year-old Children
Time frame: Day 29 and Day 50 post vaccination
Geometric Mean Ratio After Two Doses of the Cell-derived or the Egg-derived Vaccine in 3 to 8 Year-old Children
Time frame: Day 29 and Day 50 post vaccination
Percentages of Subjects Who Achieved HI Titers ≥40 After Two Doses of the Cell Culture Derived or the Egg Derived Influenza Vaccine in 3 to 8 Year-old Children
Time frame: Day 29 and Day 50 post vaccination
Percentages of Subjects Who Achieved Seroconversion or Significant Increase in HI Titers After Two Doses of the Cell Culture-derived Vaccine or the Egg-derived Influenza Vaccine in 3 to 8 Year-old Children
Time frame: Day 29 and Day 50 post vaccination
Number of Subjects Reporting Local and Systemic Reactions After 1 Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in 9 to 17 Year-old Children and Adolescents.
Time frame: up to 7 days after vaccination
Number of Subjects Reporting Local and Systemic Reactions After One and Two Doses of the Cell Culture-derived Vaccine or Egg-derived Influenza Vaccine in 3 to 8 Year-old Children.
Time frame: up to 7 days after each vaccination

Results and safety

Results posted to the registry on 16 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1+2 cTIV (9-17 Years)	656	643
Cohort 1+2 eTIV (9-17 Years)	318	312
Cohort 3 cTIV (3-8 Years)	1,608	1,457
Cohort 3 eTIV (3-8 Years)	1,022	919

Primary outcome: Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children

Time frame: Day 50 post vaccination. Geometric mean (95% Confidence Interval). Unit: Titers

Measure	Cohort 3 cTIV (3-8 Years) n = 524	Cohort 3 eTIV (3-8 Years) n = 513
A/H1N1 (egg derived antigen assay)	407 (358 to 462)	477 (419 to 542)
A/H3N2 (egg derived antigen assay)	768 (666 to 885)	1293 (1121 to 1491)
B (egg derived antigen assay)	25 (21 to 29)	44 (38 to 51)
A/H1N1 (cell derived antigen assay) (N=522,513)	563 (501 to 634)	610 (542 to 686)
A/H3N2 (cell derived antigen assay) (N=522,513)	858 (744 to 990)	1329 (1152 to 1533)
B (cell derived antigen assay) (N=522,513)	53 (46 to 62)	62 (53 to 72)

Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Ratio of GMTs: 0.85 (95% CI 0.72 to 1.01), ANOVA
Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Ratio of GMTs: 0.59 (95% CI 0.49 to 0.72), ANOVA
Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Ratio of GMTs: 0.56 (95% CI 0.46 to 0.68), ANOVA

Population analysed: The analysis was performed on the per-protocol dataset

Primary outcome: Percentages of Subjects Who Attained Seroconversion or Significant Increase in Antibody Titers in the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children

Time frame: Day 50 post vaccination. Number (95% Confidence Interval). Unit: Percentages of subjects

Measure	Cohort 3 cTIV (3-8 Years) n = 524	Cohort 3 eTIV (3-8 Years) n = 513
A/H1N1 (egg derived antigen assay)	94 (92 to 96)	96 (94 to 97)
A/H3N2 (egg derived antigen assay)	77 (73 to 81)	86 (82 to 89)
B (egg derived antigen assay)	38 (34 to 42)	53 (49 to 58)
A/H1N1 (cell derived antigen assay) (N=522,513)	96 (93 to 97)	96 (94 to 98)
A/H3N2 (cell derived antigen assay) (N=522,513)	80 (76 to 83)	85 (82 to 88)
B (cell derived antigen assay) (N=522,513)	58 (54 to 63)	58 (54 to 63)

Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Difference in % (cTIV minus eTIV): -1 (95% CI -4 to 1), binomial or the method of Miettinen and
Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Difference % (cTIV - eTIV): -9 (95% CI -13 to -4), binomial or Miettinen & Nurimen method
Cohort 3 cTIV (3-8 Years) vs Cohort 3 eTIV (3-8 Years): Difference % (cTIV minus eTIV): -15 (95% CI -21 to -9), binominal or Miettinen &Nurimen method

Population analysed: The analysis was performed on the per-protocol dataset

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout the study period (Day 1-181 for Cohorts 1 and 2, and Day 1-209 for cohort 3). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1+2 cTIV (9-17 Years)	5 of 652 (0.8%)	328 of 652 (50.3%)	Not reported
Cohort 1+2 eTIV (9-17 Years)	3 of 316 (0.9%)	168 of 316 (53.2%)	Not reported
Cohort 3 cTIV (3-8 Yrs; 1st Vaccination)	2 of 1,599 (0.1%)	799 of 1,599 (50%)	Not reported
Cohort 3 eTIV (3-8 Yrs; 1st Vaccination)	0 of 1,013 (0%)	507 of 1,013 (50%)	Not reported
Cohort 3 cTIV (3-8 Yrs; 2nd Vaccination)	7 of 1,557 (0.4%)	670 of 1,557 (43%)	Not reported
Cohort 3 eTIV (3-8 Yrs; 2nd Vaccination)	5 of 977 (0.5%)	413 of 977 (42.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22301476Vesikari T, Block SL, Guerra F, Lattanzi M, Holmes S, Izu A, Gaitatzis N, Hilbert AK, Groth N. Immunogenicity, safety and reactogenicity of a mammalian cell-culture-derived influenza vaccine in healthy children and adolescents three to seventeen years of age. Pediatr Infect Dis J. 2012 May;31(5):494-500. doi: 10.1097/INF.0b013e31824bb179.

Related trials for Influenza

RecruitingPhase 2
COVID-19 Booster and IIV Schedule in Immunocompromised Hosts
COVID 19, Influenza
RecruitingPhase 2
BPL-1357 Against H1N1 Influenza Virus Challenge
Influenza, Human
Recruiting
Light-based Immunomodulation for Guarding Against Human Respiratory Tract Infections
COVID-19 Respiratory Infection, Influenza
Not yet recruiting
Family Physician Nudges for Influenza Vaccination Among Older Adults
Influenza Vaccination
Not yet recruitingPhase 2/3
Evaluation of the Efficacy and Safety of 102D-6 in the Treatment of Acute Uncomplicated Influenza
Influenza, Human

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Vaccines study chair

Novartis Vaccines

60 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cell culture-derived influenza subunit vaccine (cTIV) and Egg derived influenza subunit vaccine (eTIV) in people with Influenza, run by Novartis at 60 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in United States, Finland, Croatia, Hungary, Lithuania and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Geometric Mean Titers of the Cell Culture-derived Vaccine Compared With the Egg-derived Vaccine in 3 to 8 Year-old Children (time frame: Day 50 post vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00645411, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2015; AzTrials last refreshed its copy on 26 Oct 2026.