InfluenzaPhase 3NCT01998477

A Study to Evaluate the Safety of Two Influenza Vaccines in Children and Adolescents 3 to <18 Years of Age at Risk for Influenza-Related Complications

A Phase 3 study testing TIVc and TIV in people with Influenza, run by Novartis Vaccines at 16 sites in 2 countries.

Completed

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

Trial summary

The study is designed to evaluate the safety of TIVc or TIV vaccine in children 3 to < 18 years of age who are at risk of complications of influenza disease due to underlying diseases. Read more about this study

Who is it for?: Ages 3 to 17 yearsHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: TIVc and TIV
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 430 participants
Where: 16 sitesin 2 countries
Study dates: Oct 2013to Jul 2014
Phase: Phase 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

Individuals 3 to <18 years of age with underlying medical conditions that indicate an increased risk of complications from influenza infection.
Further eligibility criteria may be discussed by contacting the site(s)

Who cannot join

Individuals with any fatal prognosis of an underlying medical condition (<12 month life expectancy).
Individuals hospitalized at the time of enrolment.
Individuals with a history of any anaphylaxis, serious vaccine reactions, or hypersensitivity to any of the vaccine components.
Further eligibility criteria may be discussed by contacting the site(s)

Trial locations and contacts

16 sites in 2 countries.

Country

City, postcode or hospital

16 sites in 2 countries

Spain12 sites

Novartis Investigational Site 031
Badalona, Barcelona, 8916
Novartis Investigational Site 017
Burriana, Castellon, 12530
Novartis Investigational Site 016
Castellon, Castellon, 12004
Novartis Investigational Site 015
L'Eliana, Valencia, 46183
Novartis Investigational Site 030
Madrid, 28050
Novartis Investigational Site 011
Málaga, 29011
Novartis Investigational Site 010
Marbella, Malaga, 29603
Novartis Investigational Site 013
Paiporta, Valencia, 46200
Novartis Investigational Site 018
Quart de Poblet, Valencia, 46930
Novartis Investigational Site 019
Valencia, 46017
Novartis Investigational Site 014
Valencia, 46020
Novartis Investigational Site 012
Valencia, 46024

Other trials in Spain

Italy4 sites

Novartis Investigational Site 022
Florence, 50139
Novartis Investigational Site 020
Genova, 16132
Novartis Investigational Site 021
Milan, 20157
Novartis Investigational Site 023
Roma, 165

Other trials in Italy

About this study

Official title: A Phase III, Observer-Blind, Randomized Multicenter Study to Evaluate the Safety of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture (TIVc) or in Embryonated Eggs (TIV), in Children and Adolescents 3 to <18 Years of Age at Risk for Influenza-Related Complications

The study is designed to evaluate the safety of TIVc or TIV vaccine in children 3 to < 18 years of age who are at risk of complications of influenza disease due to underlying diseases.

Conditions: Influenza
Being tested: TIVc, TIV
Keywords: Influenza, Vaccine, Flu, Children, Adolescents
Medical subject headings: Influenza, Human

What participants receive

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

TIVcBiological
Madin Darby Canine Kidney (MDCK) cell culture derived subunit influenza vaccine TIVc contained the purified viral envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA) derived from 3 strains (including HA for each strain [A/H1N1-like, A/H3N2-like, and B-like]) intramuscular (IM) injection recommended by the WHO for the 2013-2014 influenza season in the Northern Hemisphere
TIVBiological
A conventional egg derived subunit influenza vaccine (TIV) contained the purified viral envelope-glycoproteins, HA and NA derived from 3 strains (including HA for each strain [A/ H1N1-like, A/H3N2-like, and B-like]) IM injection recommended by the WHO for the 2013-2014 influenza season in the Northern Hemisphere.

Study groups in NCT01998477
Study group	Role	What they receive
TIVc	Experimental	flu vaccine Receives: Biological: TIVc
TIV	Active comparator	flu vaccine Receives: Biological: TIV

What is being measured

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

Number of Subjects Reporting Solicited Adverse Events (AEs) Following Vaccination With Either TIVc or TIV by Overall Age Group
Safety was assessed in terms of number of the subjects (3 to < 18 years of age) who reported solicited local, systemic AEs as well as other solicited AEs after receiving one or two doses of either TIVc or TIV
Measured: Day 1 through Day 7 post injection 1 and Day 29 through Day 35 post injection 2
Number of Subjects Reporting Solicited Adverse Events (AEs), Following Vaccination With Either TIVc or TIV by Age Sub-strata
Safety was assessed in terms of number of the subjects (3 to <6 years,(≥ 6 to < 9 years and 9 to <18 Years of age) who reported solicited local, systemic AEs as well as other solicited AEs after receiving one or two doses of either TIVc or TIV
Measured: Day 1 through Day 7 after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With Either TIVc or TIV by Overall Age Group and Age Sub-strata
Safety was assessed in terms of number of subjects who reported any unsolicited AEs (four weeks after 1st vaccination and up to three weeks after 2nd vaccination), serious adverse events (SAEs), new onset of chronic diseases (NOCD), medically attended AEs and AEs leading to vaccine/study withdrawal after receiving one or two doses of either TIVc or TIV by overall age group (3 to <18 years) and age sub-strata (3 to <9 years and 9 to <18 years)
Measured: Day 1 -Day 181(one dose group) Day 1 -Day 209(two dose group)

Timeline

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

Oct 2013Jul 2014

First posted29 Nov 2013 (estimated)
Study startOct 2013
Primary completionJul 2014
Study completionJul 2014

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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 430 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01998477
Sponsor's protocol ID: V58P15
Other IDs: 2013-002080-26
Status last verified: Apr 2017
First submitted: 30 Oct 2013
Last updated: 21 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Diez-Domingo J, de Martino M, Lopez JG, Zuccotti GV, Icardi G, Villani A, Moreno-Perez D, Hernandez MM, Aldean JA, Mateen AA, Enweonye I, de Rooij R, Chandra R. Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications. Int J Infect Dis. 2016 Aug;49:171-8. doi: 10.1016/j.ijid.2016.06.018. Epub 2016 Jun 23.
PubMed 27343983

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

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Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Observer-Blind, Randomized Multicenter Study to Evaluate the Safety of Trivalent Subunit Influenza Vaccines, Produced Either in Mammalian Cell Culture (TIVc) or in Embryonated Eggs (TIV), in Children and Adolescents 3 to <18 Years of Age at Risk for Influenza-Related Complications
ClinicalTrials.gov ID: NCT01998477
Acronym / sponsor ID: V58P15
Conditions: Influenza
Keywords: Influenza, Vaccine, Flu, Children, Adolescents
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 430 participants (actual)
Lead sponsor: Novartis VaccinesIndustry (pharma, biotech, devices)
Study start: Oct 2013
Primary completion: Jul 2014 (actual)
Study completion: Jul 2014 (actual)
First posted: 29 Nov 2013 (estimated)
Results: Posted 21 Apr 2017

Clinical summary

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

The study is designed to evaluate the safety of TIVc or TIV vaccine in children 3 to < 18 years of age who are at risk of complications of influenza disease due to underlying diseases.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
TIVc	Experimental	Biological: TIVcflu vaccine
TIV	Active comparator	Biological: TIVflu vaccine

Who may qualify

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

Key inclusion criteria (2 listed)

Individuals 3 to <18 years of age with underlying medical conditions that indicate an increased risk of complications from influenza infection.
Further eligibility criteria may be discussed by contacting the site(s)

Key exclusion criteria (4 listed)

Individuals with any fatal prognosis of an underlying medical condition (<12 month life expectancy).
Individuals hospitalized at the time of enrolment.
Individuals with a history of any anaphylaxis, serious vaccine reactions, or hypersensitivity to any of the vaccine components.
Further eligibility criteria may be discussed by contacting the site(s)

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
TIVcMadin Darby Canine Kidney (MDCK) cell culture derived subunit influenza vaccine TIVc contained the purified viral envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA) derived from 3 strains (including HA for each strain [A/H1N1-like, A/H3N2-like, and B-like]) intramuscular (IM) injection recommended by the WHO for the 2013-2014 influenza season in the Northern Hemisphere	Biological	TIVc
TIVA conventional egg derived subunit influenza vaccine (TIV) contained the purified viral envelope-glycoproteins, HA and NA derived from 3 strains (including HA for each strain [A/ H1N1-like, A/H3N2-like, and B-like]) IM injection recommended by the WHO for the 2013-2014 influenza season in the Northern Hemisphere.	Biological	TIV

Primary outcome

Number of Subjects Reporting Solicited Adverse Events (AEs) Following Vaccination With Either TIVc or TIV by Overall Age Group
Time frame: Day 1 through Day 7 post injection 1 and Day 29 through Day 35 post injection 2
Safety was assessed in terms of number of the subjects (3 to < 18 years of age) who reported solicited local, systemic AEs as well as other solicited AEs after receiving one or two doses of either TIVc or TIV
Number of Subjects Reporting Solicited Adverse Events (AEs), Following Vaccination With Either TIVc or TIV by Age Sub-strata
Time frame: Day 1 through Day 7 after any vaccination
Safety was assessed in terms of number of the subjects (3 to <6 years,(≥ 6 to < 9 years and 9 to <18 Years of age) who reported solicited local, systemic AEs as well as other solicited AEs after receiving one or two doses of either TIVc or TIV
Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With Either TIVc or TIV by Overall Age Group and Age Sub-strata
Time frame: Day 1 -Day 181(one dose group) Day 1 -Day 209(two dose group)
Safety was assessed in terms of number of subjects who reported any unsolicited AEs (four weeks after 1st vaccination and up to three weeks after 2nd vaccination), serious adverse events (SAEs), new onset of chronic diseases (NOCD), medically attended AEs and AEs leading to vaccine/study withdrawal after receiving one or two doses of either TIVc or TIV by overall age group (3 to <18 years) and age sub-strata (3 to <9 years and 9 to <18 years)

Results and safety

Results posted to the registry on 21 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TIVc (3 to <18 Years)	282	272
TIV (3 to <18 Years)	148	143

Primary outcome: Number of Subjects Reporting Solicited Adverse Events (AEs) Following Vaccination With Either TIVc or TIV by Overall Age Group

Time frame: Day 1 through Day 7 post injection 1 and Day 29 through Day 35 post injection 2. Number. Unit: Subjects

Measure	TIVc _inj 1 (3 to <18 Years) n = 277	TIVc_inj 2 (3 to <18 Years) n = 83	TIV_inj 1 (3 to <18 Years) n = 145	TIV_inj 2 (3 to <18 Years) n = 40
Any Local	149	41	89	18
Injection Site Tenderness	25	20	17	6
Injection Site Pain	106	19	65	8
Injection site erythema ,< 6 years	8	3	4	4
Injection site induration < 6 years	7	5	4	3
Injection site ecchymosis < 6 years	6	1	3	3
Injection site erythema >=6 years	16	5	22	3
Injection site induration >=6years	22	3	23	3

Population analysed: Analysis was done on safety dataset, i.e. the subjects in the Exposed Set who provided post-vaccination solicited AE data

Primary outcome: Number of Subjects Reporting Solicited Adverse Events (AEs), Following Vaccination With Either TIVc or TIV by Age Sub-strata

Time frame: Day 1 through Day 7 after any vaccination. Number. Unit: Subjects

Measure	TIVc_Non naive_inj 1 (3 to <6 Years) n = 28	TIVc_naive_inj 1 (3 to <6 Years) n = 50	TIVc_naive_inj 2 (3 to <6 Years) n = 50	TIV_Non naive_inj 1 (3 to <6 Years) n = 19	TIV_naive_inj 1 (3 to <6 Years) n = 15	TIV_naive_inj 2 (3 to <6 Years) n = 15	TIVc_Non naive_Inj 1 (≥ 6 to < 9 Years) n = 26	TIVc_Naive_inj 1 (≥ 6 to < 9 Years) n = 35	TIVc_Naive_inj 2 (≥ 6 to < 9 Years) n = 33	TIV_Non Naive_inj 1 (≥ 6 to < 9 Years) n = 16	TIV_Naive_inj 1 (≥ 6 to < 9 Years) n = 23	TIV_Naive_inj 2 (≥ 6 to < 9 Years) n = 24	TIVc_Non Naive (9 to <18 Years) n = 138	TIV_Non Naive (9 to <18 Years) n = 72
Any Local	14	19	22	12	7	7	16	19	19	8	13	11	81	49
Tenderness(N=28,49,49,19,15,15,0,0,0,0,0,0,0,0)	10	15	20	11	6	6	0	0	0	0	0	0	0	0
Pain(N=0,0,0,0,0,0,26,32,31,16,22,22,138,72)	0	0	0	0	0	0	15	18	19	8	10	8	73	47
Erythema27,50,50,18,15,15,26,34,32,16,23,23,131,61	7	1	3	4	0	4	1	3	5	4	5	3	5	2
Injection site induration	2	5	5	2	2	3	1	4	3	3

Population analysed: Analysis was done on safety dataset

Primary outcome: Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With Either TIVc or TIV by Overall Age Group and Age Sub-strata

Time frame: Day 1 -Day 181(one dose group) Day 1 -Day 209(two dose group). Number. Unit: Subjects

Measure	TIVc (3 to <18 Years) n = 278	TIV (3 to <18 Years) n = 148	TIVc_Naive (3 to <9 Years) n = 85	TIVc_Non Naive (3 to <9 Years) n = 54	TIVc_Non Naive (9 to <18 Years) n = 139	TIV_Naive (3 to <9 Years) n = 39	TIV_Non Naive (3 to <9 Years) n = 35	TIV_Non Naive (9 to <18 Years) n = 74
Any AEs	213	111	77	46	90	32	29	50
Any possibly related AEs	17	12	7	3	7	5	3	4
SAEs	12	4	4	2	6	0	2	2
Possibly or probably related SAE	0	0	0	0	0	0	0	0
AEs leading to NOCD	3	1	1	0	2	0	1	0
Medically Attended AEs	187	94	71	38	78	28	24	42
AEs leading to vaccine/study withdrawal	0	0	0	0	0	0	0	0
Deaths	0	0	0	0	0	0	0	0

Population analysed: Analysis was done on unsolicited safety dataset, i.e. all subjects in the Exposed Set who have post-vaccination unsolicited AE records (even if no AEs have occurred)

Adverse events

Time frame: Solicited local,systemic AEs collected -day 1 through Day 7 post injection 1 and Day 29 through Day 35 post injection 2, unsolicited AEs -Day 1 through Day 29 post 1st vaccination and Day 29 to Day 57 post 2nd vaccination. SAEs Day 1 through end of study. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TIVc (3 to <18 Years)	12 of 278 (4.3%)	246 of 278 (88.5%)	Not reported
TIV (3 to <18 Years)	4 of 148 (2.7%)	126 of 148 (85.1%)	Not reported
Total	16 of 426 (3.8%)	372 of 426 (87.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27343983Diez-Domingo J, de Martino M, Lopez JG, Zuccotti GV, Icardi G, Villani A, Moreno-Perez D, Hernandez MM, Aldean JA, Mateen AA, Enweonye I, de Rooij R, Chandra R. Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications. Int J Infect Dis. 2016 Aug;49:171-8. doi: 10.1016/j.ijid.2016.06.018. Epub 2016 Jun 23.

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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

16 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TIVc and TIV in people with Influenza, run by Novartis Vaccines at 16 sites in 2 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 2 inclusion and 4 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 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Spain, Italy. 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 phase mean?

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 21 Apr 2017). 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?

Number of Subjects Reporting Solicited Adverse Events (AEs) Following Vaccination With Either TIVc or TIV by Overall Age Group (time frame: Day 1 through Day 7 post injection 1 and Day 29 through Day 35 post injection 2). The study lists 3 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 NCT01998477, 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 21 Apr 2017.