InfluenzaPhase 1NCT00798343
Heterosubtypic Immune Responses to Influenza in Older People
A Phase 1 study testing Seasonal vaccine and H5 vaccine in people with Influenza, run by University Hospitals, Leicester at 1 site in United Kingdom.
Trial summary
Vaccination is the principal means of combating epidemic and pandemic influenza. As vaccines induce relatively strain-specific and short-lived antibody responses, annual immunisation with regularly updated vaccine is recommended for seasonal influenza, but would not be expected to protect against a pandemic event. 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?
- Seasonal vaccine and H5 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 292 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2009to Sep 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Subjects aged over 18 years of age, mentally competent, who have signed an informed consent form after having received a detailed explanation of the study protocol;
- Subjects willing to be enrolled in the vaccine study if appropriate from prescreening blood test results
- In good health as determined by:
- medical history,
- physical examination,
- clinical judgment of the Investigator;
- Able to understand and comply with all study procedures and to complete study diaries, can be contacted, and will be available for study visits
Who cannot join
- Receipt of another investigational agent within 4 weeks, 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;
- Subjects who experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) within the past 7 days before Visit 1 or any visit where trial vaccination is planned;
- Subjects who experienced fever (within 3 days prior to Visit 1;
- Subjects who are pregnant or breastfeeding;
- Females of childbearing potential who refuse to use an acceptable method of birth control for the duration of the study.
- Subjects with any serious disease, such as:
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- cancer,
- autoimmune disease (including rheumatoid arthritis),
- progressive chronic pulmonary disease (stable controlled respiratory disease including asthma is allowed),
- acute or progressive hepatic disease,
- acute or progressive renal disease;
- Subjects for whom elective surgery is planned during the study period;
- Subjects with bleeding diathesis;
- Subjects with hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccine;
- Subjects with a history of any neurological symptoms or signs, or anaphylactic shock following administration of any vaccine;
- Subjects with known or suspected impairment/alteration of immune function, for example, resulting from:
- receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy),
- receipt of immunostimulants,
- 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,
- high risk for developing an immunocompromising disease;
- Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
- Subjects with a history of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
- Subjects with any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
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Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Leicester
Leicester, Leicestershire, LE1 5WW
About this study
Official title: Evaluation of Heterosubtypic Immune Responses in Older People Before and After Seasonal and Pandemic Influenza Vaccination
Vaccination is the principal means of combating epidemic and pandemic influenza. As vaccines induce relatively strain-specific and short-lived antibody responses, annual immunisation with regularly updated vaccine is recommended for seasonal influenza, but would not be expected to protect against a pandemic event. In clinical trials among young adults, at least two doses of avian influenza H5 or H9 subunit vaccine are needed to induce moderate antibody responses. However, studies including older subjects have unexpectedly found that some people aged over 65 yrs have pre-vaccination neutralising antibody to influenza H5 and H9 respectively. These subjects mount a robust antibody response to single dose H5 or H9 pandemic vaccine, suggesting that they are effectively primed to at least some strains of avian influenza.
This exploratory proposal focuses on those elderly subjects whose immune systems already exhibit antibodies to H5 with a goal of investigating the humoral and cellular basis of the immune response to seasonal and pandemic vaccination. We will examine neutralising antibody responses to a range of human and non-human influenza viruses before and after seasonal and pandemic vaccination and evaluate cellular B and T cell immune responses before and after pandemic H5 vaccination
Read the detailed description
STUDY OBJECTIVES:
Immunological objectives
- To evaluate heterosubtypic neutralising antibody to influenza viruses in older people
- To evaluate heterosubtypic neutralising antibody responses to human and non-human influenza viruses following seasonal influenza vaccine
- To evaluate homologous and heterosubtypic neutralising antibody responses to human and non-human influenza viruses after MF59-adjuvanted H5N1 vaccine;
- To evaluate cellular B and T cell responses to influenza H5 in non-exposed subjects who exhibit anti-H5 neutralising antibodies before and after seasonal (TIV) or pandemic H5 vaccination
- To identify epitopes on the influenza haemagglutinin to which anti-H5 neutralising antibodies in sera from non-exposed subjects are directed Safety Objectives
- To evaluate safety of one or two IM doses of MF59-adjuvanted A/Vietnam/1194/2004 (H5N1) influenza vaccine, containing 7.5 μg of H5 antigen in adult subjects
- To evaluate safety of one IM dose of seasonal influenza vaccine, containing 15 μg of H1, H3 and B antigen in adult subjects
Hypotheses:
- Heterosubtypic cross reacting antibodies to influenza exist in some elderly subjects and can be boosted by a single dose of (a) seasonal TIV or (b) pandemic influenza vaccination
- Heterosubtypic cross reacting antibodies to influenza do not exist in younger subjects and cannot be induced by (a) seasonal TIV or (b) pandemic influenza vaccination
- Conditions
- Influenza
- Being tested
- Seasonal vaccine, H5 vaccine
- Keywords
- Influenza, heterosubtypic immune responses
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seasonal vaccineBiological
Also called Aggripal
Non-adjuvanted seasonal influenza vaccine (total dose 45ug)
H5 vaccineBiological
Also called Aflunov
MF59-adjuvanted A/Vietnam/1194 H5N1 vaccine 7.5ug dose
| Study group | Role | What they receive |
|---|---|---|
| Seasonal vaccine | Active comparator | Seasonal influenza vaccination Receives: Biological: Seasonal vaccine |
| Pandemic vaccine | Experimental | MF59-adjuvanted H5N1 monovalent vaccine Receives: Biological: H5 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutralising antibody to influenza subtypes
Measured: 18 months
Secondary outcomes (1)
Reactogenicity (local and systemic) to H5N1 vaccine
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2008 (estimated)
- Study startJan 2009
- Primary completionMar 2010
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 292 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals, Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Public Health England, Novartis
- Responsible party
- Sponsor
- Investigators
- Iain Stephenson, FRCP, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00798343
- Sponsor's protocol ID
- UHL10548
- Other IDs
- MRC 82292
- Status last verified
- Jun 2014
- First submitted
- 25 Nov 2008
- Last updated
- 3 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Heterosubtypic Immune Responses in Older People Before and After Seasonal and Pandemic Influenza Vaccination
- ClinicalTrials.gov ID
- NCT00798343
- Acronym / sponsor ID
- UHL10548
- Conditions
- Influenza
- Keywords
- Influenza, heterosubtypic immune responses
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 292 participants (actual)
- Lead sponsor
- University Hospitals, LeicesterUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, Public Health England, Novartis
- Study start
- Jan 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 26 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vaccination is the principal means of combating epidemic and pandemic influenza. As vaccines induce relatively strain-specific and short-lived antibody responses, annual immunisation with regularly updated vaccine is recommended for seasonal influenza, but would not be expected to protect against a pandemic event. In clinical trials among young adults, at least two doses of avian influenza H5 or H9 subunit vaccine are needed to induce moderate antibody responses. However, studies including older subjects have unexpectedly found that some people aged over 65 yrs have pre-vaccination neutralising antibody to influenza H5 and H9 respectively. These subjects mount a robust antibody response to single dose H5 or H9 pandemic vaccine, suggesting that they are effectively primed to at least some strains of avian influenza.
This exploratory proposal focuses on those elderly subjects whose immune systems already exhibit antibodies to H5 with a goal of investigating the humoral and cellular basis of the immune response to seasonal and pandemic vaccination. We will examine neutralising antibody responses to a range of human and non-human influenza viruses before and after seasonal and pandemic vaccination and evaluate cellular B and T cell immune responses before and after pandemic H5 vaccination
Detailed description
STUDY OBJECTIVES:
Immunological objectives
- To evaluate heterosubtypic neutralising antibody to influenza viruses in older people
- To evaluate heterosubtypic neutralising antibody responses to human and non-human influenza viruses following seasonal influenza vaccine
- To evaluate homologous and heterosubtypic neutralising antibody responses to human and non-human influenza viruses after MF59-adjuvanted H5N1 vaccine;
- To evaluate cellular B and T cell responses to influenza H5 in non-exposed subjects who exhibit anti-H5 neutralising antibodies before and after seasonal (TIV) or pandemic H5 vaccination
- To identify epitopes on the influenza haemagglutinin to which anti-H5 neutralising antibodies in sera from non-exposed subjects are directed Safety Objectives
- To evaluate safety of one or two IM doses of MF59-adjuvanted A/Vietnam/1194/2004 (H5N1) influenza vaccine, containing 7.5 μg of H5 antigen in adult subjects
- To evaluate safety of one IM dose of seasonal influenza vaccine, containing 15 μg of H1, H3 and B antigen in adult subjects
Hypotheses:
- Heterosubtypic cross reacting antibodies to influenza exist in some elderly subjects and can be boosted by a single dose of (a) seasonal TIV or (b) pandemic influenza vaccination
- Heterosubtypic cross reacting antibodies to influenza do not exist in younger subjects and cannot be induced by (a) seasonal TIV or (b) pandemic influenza vaccination
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Seasonal vaccine | Active comparator | Biological: Seasonal vaccineSeasonal influenza vaccination |
| Pandemic vaccine | Experimental | Biological: H5 vaccineMF59-adjuvanted H5N1 monovalent vaccine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects aged over 18 years of age, mentally competent, who have signed an informed consent form after having received a detailed explanation of the study protocol;
- Subjects willing to be enrolled in the vaccine study if appropriate from prescreening blood test results
- In good health as determined by:
- Able to understand and comply with all study procedures and to complete study diaries, can be contacted, and will be available for study visits
Key exclusion criteria (24 listed)
- Receipt of another investigational agent within 4 weeks, 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;
- Subjects who experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) within the past 7 days before Visit 1 or any visit where trial vaccination is planned;
- Subjects who experienced fever (within 3 days prior to Visit 1;
- Subjects who are pregnant or breastfeeding;
- Females of childbearing potential who refuse to use an acceptable method of birth control for the duration of the study.
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 |
|---|---|---|
| Seasonal vaccineAlso: AggripalNon-adjuvanted seasonal influenza vaccine (total dose 45ug) | Biological | Seasonal vaccine |
| H5 vaccineAlso: AflunovMF59-adjuvanted A/Vietnam/1194 H5N1 vaccine 7.5ug dose | Biological | Pandemic vaccine |
Primary outcome
Neutralising antibody to influenza subtypes
Time frame: 18 months
1 secondary outcome
Reactogenicity (local and systemic) to H5N1 vaccine
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2014.
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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.
Iain Stephenson, FRCP principal investigator
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Seasonal vaccine and H5 vaccine in people with Influenza, run by University Hospitals, Leicester at 1 site in United Kingdom.
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 7 inclusion and 24 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 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Neutralising antibody to influenza subtypes (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2014.