Pandemic H5N1 InfluenzaPhase 2NCT01776541
Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Healthy Adults
A Phase 2 study testing Adjuvanted H5N1 pandemic influenza vaccine in people with Pandemic H5N1 Influenza, run by Novartis Vaccines at 8 sites in 3 countries.
Trial summary
Evaluate Safety, Tolerability and Immune Response of Adjuvanted H5N1 Cell Culture Derived Influenza Vaccine in Adult Subjects. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Pandemic H5N1 Influenza
- What is being tested?
- Adjuvanted H5N1 pandemic influenza vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 979 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Jan 2013to May 2014
- Phase
- Phase 2
- 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 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult subjects 18 to 64 years of age,
- Individuals willing to provide written informed consent,
- Individuals in good health,
- Individuals willing to allow for their serum samples to be stored beyond the study period.
Who cannot join
- Individuals not able to understand and follow study procedures,
- History of any significant illness,
- History of any chronic medical condition or progressive disease,
- Presence of medically significant cancer,
- Known or suspected impairment/alteration of immune function,
- Presence of any progressive or severe neurologic disorder,
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- Presence of any bleeding disorders or conditions that prolongs bleeding time,
- History of allergy to vaccine components,
- Receipt of any other investigational product within 30 days prior to entry into the study,
- History of previous H5N1 vaccination,
- Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study,
- Receipt of any other vaccine within 2 weeks prior to entry into the study
- Body temperature ≥38°C.0 (≥100.4° F) and/or acute illness within 3 days of intended study vaccination,
- Pregnant or breast feeding,
- Females of childbearing potential refusing to use acceptable method of birth control,
- Body mass index (BMI) ≥ 35 kg/m2,
- History of drug or alcohol abuse,
- Any planned surgery during study period,
- Individuals conducting the study and their immediate family members,
- Individuals with behavioral or cognitive impairment or psychiatric diseases.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
4 Benchmark Medical Research
Austin, Texas, 78705
1 Miami Research Associates
Miami, Florida, 33143
2 Mercy Health Research
St Louis, Missouri, 63141
3 Saint Louis University
St Louis, Missouri, 63141
Australia3 sites
46 CMAX
Adelaide, South Australia, 5000
47 Linear Clinical Research
Nedlands, Western Australia, 6009
48 Hunter Clinical Research
Newcastle, New South Wales, 2292
About this study
Official title: A Phase II, Randomized, Observer-Blind,Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenza Virus Vaccine at Two Different Formulations in Healthy Adult Subjects.
Evaluate Safety, Tolerability and Immune Response of Adjuvanted H5N1 Cell Culture Derived Influenza Vaccine in Adult Subjects.
- Conditions
- Pandemic H5N1 Influenza
- Being tested
- Adjuvanted H5N1 pandemic influenza vaccine
- Keywords
- Influenza, Pandemic, H5N1, Adults
- Medical subject headings
- Influenza, Human, Influenza in Birds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvanted H5N1 pandemic influenza vaccineBiological
Comparison of two doses of aH5N1c vaccine
| Study group | Role | What they receive |
|---|---|---|
| aH5N1c-High Dose | Experimental | Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Receives: Biological: Adjuvanted H5N1 pandemic influenza vaccine |
| aH5N1c-Low dose | Experimental | Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. Receives: Biological: Adjuvanted H5N1 pandemic influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.
The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion.
CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
Measured: Three weeks after 2nd vaccination (day 43)
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion.
Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.
CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
Measured: Three weeks after 2nd vaccination (day 43)
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.
Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.
Measured: From day 1 through day 7 after any vaccination.
Number of Subjects Reporting Unsolicited AEs After Any Vaccination.
Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.
Measured: Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387
Secondary outcomes (3)
Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.
Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported.
The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age.
Measured: Day 1; day 22; day 43 and day 387
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.
Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion.
European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.
Measured: Day 1, day 22, day 43 and day 387
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.
Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.
The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.
Measured: Day 22, day 43 and day 387
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionJun 2013
- Study completionMay 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 Pandemic H5N1 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 979 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Vaccines
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Department of Health and Human Services
- Responsible party
- Sponsor
- Investigators
- Novartis Vaccines and Diagnostics, Study chair, Novartis Vaccines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01776541
- Sponsor's protocol ID
- V89_04
- Status last verified
- Jan 2015
- First submitted
- 20 Jan 2013
- Last updated
- 3 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Frey SE, Shakib S, Chanthavanich P, Richmond P, Smith T, Tantawichien T, Kittel C, Jaehnig P, Mojares Z, Verma B, Kanesa-Thasan N, Hohenboken M. Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly. Open Forum Infect Dis. 2019 Mar 1;6(4):ofz107. doi: 10.1093/ofid/ofz107. eCollection 2019 Apr.
PubMed 30968056
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Observer-Blind,Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenza Virus Vaccine at Two Different Formulations in Healthy Adult Subjects.
- ClinicalTrials.gov ID
- NCT01776541
- Acronym / sponsor ID
- V89_04
- Conditions
- Pandemic H5N1 Influenza
- Keywords
- Influenza, Pandemic, H5N1, Adults
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 979 participants (actual)
- Lead sponsor
- Novartis VaccinesIndustry (pharma, biotech, devices)
- Collaborators
- Department of Health and Human Services
- Study start
- Jan 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Jan 2013 (estimated)
- Results
- Posted 3 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate Safety, Tolerability and Immune Response of Adjuvanted H5N1 Cell Culture Derived Influenza Vaccine in Adult Subjects.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| aH5N1c-High Dose | Experimental | Biological: Adjuvanted H5N1 pandemic influenza vaccineSubjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
| aH5N1c-Low dose | Experimental | Biological: Adjuvanted H5N1 pandemic influenza vaccineSubjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy adult subjects 18 to 64 years of age,
- Individuals willing to provide written informed consent,
- Individuals in good health,
- Individuals willing to allow for their serum samples to be stored beyond the study period.
Key exclusion criteria (20 listed)
- Individuals not able to understand and follow study procedures,
- History of any significant illness,
- History of any chronic medical condition or progressive disease,
- Presence of medically significant cancer,
- Known or suspected impairment/alteration of immune function,
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 |
|---|---|---|
| Adjuvanted H5N1 pandemic influenza vaccineComparison of two doses of aH5N1c vaccine | Biological | aH5N1c-High Dose, aH5N1c-Low dose |
Primary outcome
Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain.
Time frame: Three weeks after 2nd vaccination (day 43)
The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Time frame: Three weeks after 2nd vaccination (day 43)
Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination.
Time frame: From day 1 through day 7 after any vaccination.
Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine.
Number of Subjects Reporting Unsolicited AEs After Any Vaccination.
Time frame: Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387
Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.
3 secondary outcomes
Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine.
Time frame: Day 1; day 22; day 43 and day 387
Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain.
Time frame: Day 1, day 22, day 43 and day 387
Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain.
Time frame: Day 22, day 43 and day 387
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30968056Frey SE, Shakib S, Chanthavanich P, Richmond P, Smith T, Tantawichien T, Kittel C, Jaehnig P, Mojares Z, Verma B, Kanesa-Thasan N, Hohenboken M. Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly. Open Forum Infect Dis. 2019 Mar 1;6(4):ofz107. doi: 10.1093/ofid/ofz107. eCollection 2019 Apr.
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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 and Diagnostics study chair
Novartis Vaccines
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adjuvanted H5N1 pandemic influenza vaccine in people with Pandemic H5N1 Influenza, run by Novartis Vaccines at 8 sites in 3 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 4 inclusion and 20 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 3 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia, Thailand. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Feb 2015). 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 Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. (time frame: Three weeks after 2nd vaccination (day 43)). The study lists 4 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 NCT01776541, 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 3 Feb 2015.