InfluenzaPhase 3NCT00492063

Safety and Immunogenicity of a Cell Culture-derived Influenza Vaccine in Healthy Adults and Elderly

A Phase 3 study testing Cell culture-derived trivalent subunit influenza vaccine (cTIV) and Egg-derived trivalent subunit influenza vaccine (TIV) in people with Influenza, run by Novartis Vaccines at 5 sites in Poland.

Completed

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

Official record

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Trial summary

The present study aims to evaluate the safety and immunogenicity of the new influenza subunit vaccine produced in Madin Darby Canine Kidney (MDCK) cells in healthy adult and elderly subjects. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: Cell culture-derived trivalent subunit influenza vaccine (cTIV) and Egg-derived trivalent subunit influenza vaccine (TIV)
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2,654 participants
Where: 5 sitesPoland
Study dates: Sep 2004to May 2005
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 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

18 to 60 years of age (first age group) OR over 60 years of age (second age group)
mentally competent to understand the nature, the scope and the consequences of the study
able and willing to give written informed consent prior to study entry
available for all the visits scheduled in the study
residence in the study area
in good health as determined by:

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medical history,
physical examination,
clinical judgment of the investigator.

Who cannot join

unable or unwilling to give written informed consent to participate in the study
suffering from an acute infectious disease
any serious disease such as:
cancer (except for benign or localized skin cancer and non metastatic prostate cancer not currently treated with chemotherapy),_
autoimmune disease (including rheumatoid arthritis),
advanced arteriosclerotic disease or complicated diabetes mellitus,

Show all 25Show fewer

chronic obstructive pulmonary disease (COPD) requiring oxygen therapy,
acute or progressive hepatic disease,
acute or progressive renal disease,
congestive heart failure
surgery planned during the study period
bleeding diathesis
history of hypersensitivity to any component of the study medication or chemically related substances, such as allergy to eggs or egg products
known or suspected impairment/alteration of immune function resulting from:
receipt of immunosuppressive therapy (any cortical steroid or cancer chemotherapy),
receipt of immunostimulants,
receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study,
high risk for developing an immunocompromising disease within the past 6 months
history of drug or alcohol abuse
laboratory confirmed influenza disease in the past 6 months
received influenza vaccine within the past 6 months
received another vaccine or any investigational agent within the past 60 days, or planned vaccination within 3 weeks following the study vaccination
any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) or experienced fever ≥ 38°C within the past 3 days
pregnant women or women who refused to use a reliable contraceptive method throughout the study (180 days)
any condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Poland5 sites

Centrum Farmakologii Klinicznej
Krakow, 30-969
N ZOZ Jagiellonskie, Centrum Medyczne Sp. z o.o.
Os. Jagiellonskie 1, Kraków, 31-832
Praktyka Grupowa Lekarzy POZ "Familia"
Pl. Sikorskiego 6a, Kraków, 31-115
Wojewódzki Szpital Dzieciecy
Ul. Langiewicza 2, Kielce, 25-381
Szpital Jana Pawła II
Ul. Pradnicka 80, Kraków, 31-202

Other trials in Poland

About this study

Official title: A Phase III, Observer-Blind, Randomized, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture and of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult and Elderly Subjects

The present study aims to evaluate the safety and immunogenicity of the new influenza subunit vaccine produced in Madin Darby Canine Kidney (MDCK) cells in healthy adult and elderly subjects.

Conditions: Influenza
Being tested: Cell culture-derived trivalent subunit influenza vaccine (cTIV), Egg-derived trivalent subunit influenza vaccine (TIV)
Keywords: safety, immunogenicity, non-inferiority, MDCK, cell culture-derived, subunit influenza vaccine, influenza prevention
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 trivalent subunit influenza vaccine (cTIV)Biological
One vaccination (0.5 mL) of cell culture-derived influenza vaccine (cTIV) was administered in the deltoid muscle
Egg-derived trivalent subunit influenza vaccine (TIV)Biological
One vaccination (0.5 mL) of egg-derived influenza virus vaccine (TIV) was administered in the deltoid muscle

Study groups in NCT00492063
Study group	Role	What they receive
Cell culture-derived influenza vaccine (cTIV)	Experimental	Not described Receives: Biological: Cell culture-derived trivalent subunit influenza vaccine (cTIV)
Egg-derived influenza virus vaccine (TIV)	Active comparator	Not described Receives: Biological: Egg-derived trivalent subunit influenza vaccine (TIV)

What is being measured

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

Percentages Of Subjects Who Achieved HI Titer ≥40 After One Vaccination of Cell Culture-derived (cTIV) or Egg-derived (TIV) Influenza Subunit Vaccines
Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (day 1) and three weeks (day 22) after one vaccination of cTIV or TIV vaccine for each of three vaccine strains, evaluated using the hemagglutination inhibition (HI) egg-derived antigen assay.
In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the percentage of subjects achieving HI titers ≥40 is >70% in the ≥18 to ≤60 years of age group or >60% in the ≥61 years of age group.
Measured: Before vaccination (day 1) and three weeks after vaccination (day 22)
Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titer After One Vaccination of cTIV or TIV
Seroconversion or significant in HI titer is defined as the percentage of subjects with a prevaccination HI titer <10 (negative) to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, at least a 4-fold increase in postvaccination HI titer. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), the criterion is met if the percentage of subjects achieving seroconversion/significant increase is >40% in the ≥18 to ≤60 years of age group or >30% in the ≥61 years of age group.
Measured: Three weeks after vaccination (day 22)
Geometric Mean Ratio of Subjects After One Vaccination of cTIV or TIV
Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI Geometric Mean Titers (GMTs), three weeks after (day 22) one vaccination of cTIV or TIV. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the GMR (day 22/day 1) in HI antibody titer is >2.5 in the ≥18 to ≤60 years of age group or >2.0 in the ≥61 years of age group.
Measured: Three weeks after vaccination (day 22)

Secondary outcomes (1)

Number of Subjects Who Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination
The solicited local and systemic reactions were collected from day 1 up to and including day 7 after vaccination for both the vaccine groups.
Measured: Up to 7 days postvaccination

Timeline

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

Sep 2004May 2005

First posted27 Jun 2007 (estimated)
Study startSep 2004
Primary completionDec 2004
Study completionMay 2005

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: Single blind
Who is masked: Participant
Enrolment: 2,654 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00492063
Sponsor's protocol ID: V58P4
Status last verified: Dec 2015
First submitted: 26 Jun 2007
Last updated: 1 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Szymczakiewicz-Multanowska A, Groth N, Bugarini R, Lattanzi M, Casula D, Hilbert A, Tsai T, Podda A. Safety and immunogenicity of a novel influenza subunit vaccine produced in mammalian cell culture. J Infect Dis. 2009 Sep 15;200(6):841-8. doi: 10.1086/605505.
PubMed 19673651

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?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Observer-Blind, Randomized, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture and of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult and Elderly Subjects
ClinicalTrials.gov ID: NCT00492063
Acronym / sponsor ID: V58P4
Conditions: Influenza
Keywords: safety, immunogenicity, non-inferiority, MDCK, cell culture-derived, subunit influenza vaccine, influenza prevention
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,654 participants (actual)
Lead sponsor: Novartis VaccinesIndustry (pharma, biotech, devices)
Study start: Sep 2004
Primary completion: Dec 2004 (actual)
Study completion: May 2005 (actual)
First posted: 27 Jun 2007 (estimated)
Results: Posted 21 Feb 2013

Clinical summary

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

The present study aims to evaluate the safety and immunogenicity of the new influenza subunit vaccine produced in Madin Darby Canine Kidney (MDCK) cells in healthy adult and elderly subjects.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Cell culture-derived influenza vaccine (cTIV)	Experimental	Biological: Cell culture-derived trivalent subunit influenza vaccine (cTIV)
Egg-derived influenza virus vaccine (TIV)	Active comparator	Biological: Egg-derived trivalent subunit influenza vaccine (TIV)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

18 to 60 years of age (first age group) OR over 60 years of age (second age group)
mentally competent to understand the nature, the scope and the consequences of the study
able and willing to give written informed consent prior to study entry
available for all the visits scheduled in the study
residence in the study area

Key exclusion criteria (25 listed)

unable or unwilling to give written informed consent to participate in the study
suffering from an acute infectious disease
any serious disease such as:
surgery planned during the study period
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 trivalent subunit influenza vaccine (cTIV)One vaccination (0.5 mL) of cell culture-derived influenza vaccine (cTIV) was administered in the deltoid muscle	Biological	Cell culture-derived influenza vaccine (cTIV)
Egg-derived trivalent subunit influenza vaccine (TIV)One vaccination (0.5 mL) of egg-derived influenza virus vaccine (TIV) was administered in the deltoid muscle	Biological	Egg-derived influenza virus vaccine (TIV)

Primary outcome

Percentages Of Subjects Who Achieved HI Titer ≥40 After One Vaccination of Cell Culture-derived (cTIV) or Egg-derived (TIV) Influenza Subunit Vaccines
Time frame: Before vaccination (day 1) and three weeks after vaccination (day 22)
Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (day 1) and three weeks (day 22) after one vaccination of cTIV or TIV vaccine for each of three vaccine strains, evaluated using the hemagglutination inhibition (HI) egg-derived antigen assay. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the percentage of subjects achieving HI titers ≥40 is >70% in the ≥18 to ≤60 years of age group or >60% in the ≥61 years of age group.
Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titer After One Vaccination of cTIV or TIV
Time frame: Three weeks after vaccination (day 22)
Seroconversion or significant in HI titer is defined as the percentage of subjects with a prevaccination HI titer <10 (negative) to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, at least a 4-fold increase in postvaccination HI titer. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), the criterion is met if the percentage of subjects achieving seroconversion/significant increase is >40% in the ≥18 to ≤60 years of age group or >30% in the ≥61 years of age group.
Geometric Mean Ratio of Subjects After One Vaccination of cTIV or TIV
Time frame: Three weeks after vaccination (day 22)
Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI Geometric Mean Titers (GMTs), three weeks after (day 22) one vaccination of cTIV or TIV. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the GMR (day 22/day 1) in HI antibody titer is >2.5 in the ≥18 to ≤60 years of age group or >2.0 in the ≥61 years of age group.

1 secondary outcome

Number of Subjects Who Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination
Time frame: Up to 7 days postvaccination

Results and safety

Results posted to the registry on 21 Feb 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
cTIV (Adults)	652	642
TIV (Adults)	648	634
cTIV (Elderly)	678	667
TIV (Elderly)	676	666

Primary outcome: Percentages Of Subjects Who Achieved HI Titer ≥40 After One Vaccination of Cell Culture-derived (cTIV) or Egg-derived (TIV) Influenza Subunit Vaccines

Time frame: Before vaccination (day 1) and three weeks after vaccination (day 22). Number (95% Confidence Interval). Unit: Percentages

Measure	cTIV (Adults) n = 650	TIV (Adults) n = 644	cTIV (Elderly) n = 672	TIV (Elderly) n = 674
A/H1N1 (Day 1)	29 (26 to 33)	33 (29 to 36)	30 (27 to 34)	31 (27 to 34)
A/H1N1 (Day 22)	92 (89 to 94)	92 (89 to 94)	85 (82 to 87)	85 (82 to 88)
A/H3N2 (Day 1)	65 (61 to 69)	63 (60 to 67)	66 (63 to 70)	59 (56 to 63)
A/H3N2 (Day 22)	99 (98 to 100)	99 (98 to 99)	97 (96 to 98)	98 (97 to 99)
B (Day 1)	16 (13 to 19)	18 (15 to 22)	23 (20 to 26)	20 (17 to 23)
B (Day 22)	90 (88 to 93)	91 (88 to 93)	90 (88 to 92)	89 (87 to 91)

cTIV (Adults) vs TIV (Adults): Group difference: 0 (95% CI -3 to 3)
cTIV (Adults) vs TIV (Adults): Group difference: 0 (95% CI -1 to 2)
cTIV (Adults) vs TIV (Adults): Group difference: 0 (95% CI -3 to 3)

Population analysed: Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccination correctly; provided evaluable data before and after vaccination; and with no major protocol violations, as defined before unblinding.

Primary outcome: Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titer After One Vaccination of cTIV or TIV

Time frame: Three weeks after vaccination (day 22). Number (95% Confidence Interval). Unit: Percentages

Measure	cTIV (Adults) n = 650	TIV (Adults) n = 644	cTIV (Elderly) n = 672	TIV (Elderly) n = 674
A/H1N1	69 (65 to 73)	67 (63 to 71)	55 (51 to 59)	55 (51 to 59)
A/H3N2	63 (59 to 67)	64 (60 to 68)	68 (65 to 72)	65 (61 to 69)
B	85 (82 to 87)	81 (78 to 84)	80 (77 to 83)	73 (70 to 77)

cTIV (Adults) vs TIV (Adults): Group difference: 2 (95% CI -3 to 7)
cTIV (Adults) vs TIV (Adults): Group difference: -1 (95% CI -6 to 4)
cTIV (Adults) vs TIV (Adults): Group difference: 4 (95% CI 0 to 8)

Population analysed: Analysis was performed on the PP set.

Primary outcome: Geometric Mean Ratio of Subjects After One Vaccination of cTIV or TIV

Time frame: Three weeks after vaccination (day 22). Number (95% Confidence Interval). Unit: Ratio

Measure	cTIV (Adults) n = 650	TIV (Adults) n = 644	cTIV (Elderly) n = 672	TIV (Elderly) n = 674
A/H1N1	11 (10 to 13)	11 (9.34 to 12)	5.74 (5.15 to 6.41)	5.96 (5.35 to 6.65)
A/H3N2	5.99 (5.37 to 6.68)	7.08 (6.34 to 7.9)	7.25 (6.47 to 8.12)	8.36 (7.46 to 9.36)
B	13 (12 to 15)	12 (11 to 13)	12 (11 to 13)	9.29 (8.42 to 10)

cTIV (Adults) vs TIV (Adults): Ratio of GMRs: 1.07 (95% CI 0.9 to 1.28)
cTIV (Adults) vs TIV (Adults): Ratio of GMRs: 0.85 (95% CI 0.72 to 0.99)
cTIV (Adults) vs TIV (Adults): Ratio of GMRs: 1.14 (95% CI 0.99 to 1.3)

Population analysed: Analysis was performed on the PP set.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Throughout the study (day 1 to day 180). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
cTIV (Adults)	7 of 652 (1.1%)	261 of 652 (40%)	Not reported
TIV (Adults)	5 of 648 (0.8%)	257 of 648 (39.7%)	Not reported
cTIV (Elderly)	19 of 678 (2.8%)	224 of 678 (33%)	Not reported
TIV (Elderly)	18 of 676 (2.7%)	207 of 676 (30.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19673651Szymczakiewicz-Multanowska A, Groth N, Bugarini R, Lattanzi M, Casula D, Hilbert A, Tsai T, Podda A. Safety and immunogenicity of a novel influenza subunit vaccine produced in mammalian cell culture. J Infect Dis. 2009 Sep 15;200(6):841-8. doi: 10.1086/605505.

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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

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 25 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 1 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Poland. 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 Feb 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?

Percentages Of Subjects Who Achieved HI Titer ≥40 After One Vaccination of Cell Culture-derived (cTIV) or Egg-derived (TIV) Influenza Subunit Vaccines (time frame: Before vaccination (day 1) and three weeks after vaccination (day 22)). 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 NCT00492063, 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 1 Jan 2016.