InfluenzaPhase 2NCT00993083
A Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults
A Phase 2 study testing MVA-NP+M1 in people with Influenza, run by University of Oxford at 2 sites in United Kingdom.
Trial summary
This is a Phase IIa open label, non placebo controlled, non-randomised controlled challenge study. The primary objective of this study is to assess the safety of a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- MVA-NP+M1
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jun 2009to Mar 2010
- Phase
- Phase 2
- 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 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or females aged 18 - 45 years
- HI titre of less than 10
- In general good health determined by a screening evaluation (medical history, physical examination, vital signs electrocardiogram (ECG) and clinical safety laboratory tests). ECG and spirometry will be performed at entry into quarantine rather than at screening visit
- Females should fulfil the following criteria: (i) not pregnant or breastfeeding for the duration of the study and (ii) agree to use a reliable form of contraception for the duration of the study if sexually active
- Negative HBsAg, HIV and HCV antibody screen
- Negative class A drugs of abuse screen
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- Have not been vaccinated for Influenza virus in the current season or had a known influenza virus infection in the current season
- Give written informed consent to participate
- Willingness to remain in isolation during the challenge phase of the study and to comply with all study requirements
- Willing and able to communicate with the Investigator and understand the requirements of the study
Who cannot join
- Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use of an IMP during the study period
- Prior receipt of a recombinant MVA vaccine (vaccinees only)
- Administration of immunoglobulins and/or any blood products within the three months preceding date of enrolment.
- Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products. Any allergy to eggs or egg products
- Any history of anaphylaxis in reaction to vaccination
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- Current cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- Serious current psychiatric condition
- Any other chronic illness requiring hospital specialist supervision
- Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
- Any other significant disease, disorder or finding, which, in the opinion of the Investigators, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
- Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis (see Table 1. Values outside the stated limits of Table 1 need written comment by a physician if considered clinically insignificant).
- Venous access inadequate for phlebotomy demands of the study
- Clinically significant abnormality on ECG
- History since age 13 of asthma of any aetiology
- Smokers who are unwilling or unable to desist for the duration of the inpatient challenge component of the study
- Any anatomic or neurologic abnormality impairing the gag reflex or associated with a risk of aspiration
- Presence of febrile illness or symptoms of upper respiratory tract infection on the day of vaccination (vaccination would be deferred)
- Presence of febrile illness or symptoms suggestive of influenza between admission for influenza challenge and administration of the challenge inoculum
- Use of inhaled, topical or systemic steroids in the six months preceding date of enrolment other than occasional use of cutaneous steroid if considered clinically irrelevant to the study by the Investigator..
- Donation of blood or blood products within 7 days before study entry or at any time during the study
- Donation of plasma within 7 days of study entry
- Anti-'flu antibody titre of 10 or greater
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
Wellcome Trust Clinical Research Facility, University of Southampton
Southampton, Hampshire, SO16 6YD
About this study
Official title: A Phase IIA Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults
This is a Phase IIa open label, non placebo controlled, non-randomised controlled challenge study. The primary objective of this study is to assess the safety of a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Initially two volunteers will be vaccinated and challenged with Influenza, followed by vaccination of a further 12 volunteers and an Influenza challenge of those 12 along with 12 non-vaccinated controls.
Read the detailed description
Antibodies against the external proteins of influenza can prevent the virus from infecting cells and either prevent infection or limit the spread of infection. However the surface proteins are highly variable and there is little antibody cross-reactivity between variants. Once a cell has been infected with the virus, it is then vulnerable to T cell attack resulting in the destruction of infected cells so that no more virus can be produced and the infection is controlled. There is evidence from clinical trials of influenza challenge, and animal models that T cell responses can protect in the absence of antibodies. Additionally, since T cells can recognise the highly conserved internal proteins of influenza, cross-subtype protection can be achieved.
Seasonal influenza infection results in a T cell response to the virus which can protect against subsequent infection. However over the course of a few years these responses decline below protective levels. The new vaccine being tested in this study is designed to boost these T cell responses back to protective levels. Even responses that may be too low to be reliably quantified by currently available assays may still be boosted to high levels by a single dose of recombinant MVA. Since the internal proteins vary little between influenza subtypes, this could result in a 'universal' vaccine against influenza A. If the need to continually reformulate the vaccine in response to mutations in the viral coat proteins can be removed, the universal vaccine could be produced in large amounts and used more widely than the existing seasonal 'flu vaccines, thus protecting the population against currently circulating viruses and new virus types that are at present only found in avian species.
There is very little polymorphism of NP and M1 between influenza A isolates. NP is 92% identical between H3N2 and H1N1 strains, and 91% identical between H3N2 and H5N1 strains. M1 is 95% identical between H3N2 and H1N1 strains, and 93% identical between H3N2 and H5N1 strains. This low level of variation appears to allow strong T cell cross-reactivity.
MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most mammalian cells. Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is unimpaired. This means that MVA is an efficient single round expression vector, incapable of causing infection in mammals. Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. This safety in man is consistent with the avirulence of MVA in animal models, where recombinant MVAs have also been shown to be protectively immunogenic as vaccines against viral diseases and cancer. Importantly for a vaccine which may eventually be used in a large proportion of the population, recombinant MVAs expressing HIV antigens have been shown to be safe and immunogenic in HIV-infected subjects.
- Conditions
- Influenza
- Being tested
- MVA-NP+M1
- Keywords
- Influenza, Vaccine
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVA-NP+M1Biological
Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
| Study group | Role | What they receive |
|---|---|---|
| Vaccinated | Experimental | 14 volunteers (2 in lead safety group and 12 in main study group) to receive MVA-NP+M1 via the IM route. Volunteers will then be challenged with Influenza 30 days post vaccination. Receives: Biological: MVA-NP+M1 |
| Control | No intervention | 12 volunteers who will not receive vaccine but will also be challenged with Influenza on day 30 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of a new Influenza vaccine, MVA-NP+M1, when administered to healthy volunteers
Measured: 6 months
Secondary outcomes (1)
Cellular immune response generated by a new influenza vaccine MVA- NP+M1 when administered as a single dose to healthy adults.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2009 (estimated)
- Study startJun 2009
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Investigators
- Adrian VS Hill, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00993083
- Sponsor's protocol ID
- Flu002
- Status last verified
- Jan 2011
- First submitted
- 8 Oct 2009
- Last updated
- 11 Aug 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lillie PJ, Berthoud TK, Powell TJ, Lambe T, Mullarkey C, Spencer AJ, Hamill M, Peng Y, Blais ME, Duncan CJ, Sheehy SH, Havelock T, Faust SN, Williams RL, Gilbert A, Oxford J, Dong T, Hill AV, Gilbert SC. Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. Clin Infect Dis. 2012 Jul;55(1):19-25. doi: 10.1093/cid/cis327. Epub 2012 Mar 22.
PubMed 22441650
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Study to Assess the Safety and Efficacy of a New Influenza Candidate Vaccine MVA-NP+M1 In Healthy Adults
- ClinicalTrials.gov ID
- NCT00993083
- Acronym / sponsor ID
- Flu002
- Conditions
- Influenza
- Keywords
- Influenza, Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- Jun 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 9 Oct 2009 (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.
This is a Phase IIa open label, non placebo controlled, non-randomised controlled challenge study. The primary objective of this study is to assess the safety of a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Initially two volunteers will be vaccinated and challenged with Influenza, followed by vaccination of a further 12 volunteers and an Influenza challenge of those 12 along with 12 non-vaccinated controls.
Detailed description
Antibodies against the external proteins of influenza can prevent the virus from infecting cells and either prevent infection or limit the spread of infection. However the surface proteins are highly variable and there is little antibody cross-reactivity between variants. Once a cell has been infected with the virus, it is then vulnerable to T cell attack resulting in the destruction of infected cells so that no more virus can be produced and the infection is controlled. There is evidence from clinical trials of influenza challenge, and animal models that T cell responses can protect in the absence of antibodies. Additionally, since T cells can recognise the highly conserved internal proteins of influenza, cross-subtype protection can be achieved.
Seasonal influenza infection results in a T cell response to the virus which can protect against subsequent infection. However over the course of a few years these responses decline below protective levels. The new vaccine being tested in this study is designed to boost these T cell responses back to protective levels. Even responses that may be too low to be reliably quantified by currently available assays may still be boosted to high levels by a single dose of recombinant MVA. Since the internal proteins vary little between influenza subtypes, this could result in a 'universal' vaccine against influenza A. If the need to continually reformulate the vaccine in response to mutations in the viral coat proteins can be removed, the universal vaccine could be produced in large amounts and used more widely than the existing seasonal 'flu vaccines, thus protecting the population against currently circulating viruses and new virus types that are at present only found in avian species.
There is very little polymorphism of NP and M1 between influenza A isolates. NP is 92% identical between H3N2 and H1N1 strains, and 91% identical between H3N2 and H5N1 strains. M1 is 95% identical between H3N2 and H1N1 strains, and 93% identical between H3N2 and H5N1 strains. This low level of variation appears to allow strong T cell cross-reactivity.
MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most mammalian cells. Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is unimpaired. This means that MVA is an efficient single round expression vector, incapable of causing infection in mammals. Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. This safety in man is consistent with the avirulence of MVA in animal models, where recombinant MVAs have also been shown to be protectively immunogenic as vaccines against viral diseases and cancer. Importantly for a vaccine which may eventually be used in a large proportion of the population, recombinant MVAs expressing HIV antigens have been shown to be safe and immunogenic in HIV-infected subjects.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaccinated | Experimental | Biological: MVA-NP+M114 volunteers (2 in lead safety group and 12 in main study group) to receive MVA-NP+M1 via the IM route. Volunteers will then be challenged with Influenza 30 days post vaccination. |
| Control | No intervention | –12 volunteers who will not receive vaccine but will also be challenged with Influenza on day 30 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Male or females aged 18 - 45 years
- HI titre of less than 10
- In general good health determined by a screening evaluation (medical history, physical examination, vital signs electrocardiogram (ECG) and clinical safety laboratory tests). ECG and spirometry will be performed at entry into quarantine rather than at screening visit
- Females should fulfil the following criteria: (i) not pregnant or breastfeeding for the duration of the study and (ii) agree to use a reliable form of contraception for the duration of the study if sexually active
- Negative HBsAg, HIV and HCV antibody screen
Key exclusion criteria (23 listed)
- Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use of an IMP during the study period
- Prior receipt of a recombinant MVA vaccine (vaccinees only)
- Administration of immunoglobulins and/or any blood products within the three months preceding date of enrolment.
- Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products. Any allergy to eggs or egg products
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 |
|---|---|---|
| MVA-NP+M1Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0 | Biological | Vaccinated |
Primary outcome
Safety of a new Influenza vaccine, MVA-NP+M1, when administered to healthy volunteers
Time frame: 6 months
1 secondary outcome
Cellular immune response generated by a new influenza vaccine MVA- NP+M1 when administered as a single dose to healthy adults.
Time frame: 6 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 11 Aug 2011.
- Derived from this study: PubMed 22441650Lillie PJ, Berthoud TK, Powell TJ, Lambe T, Mullarkey C, Spencer AJ, Hamill M, Peng Y, Blais ME, Duncan CJ, Sheehy SH, Havelock T, Faust SN, Williams RL, Gilbert A, Oxford J, Dong T, Hill AV, Gilbert SC. Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. Clin Infect Dis. 2012 Jul;55(1):19-25. doi: 10.1093/cid/cis327. Epub 2012 Mar 22.
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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.
Adrian VS Hill, DPhil principal investigator
University of Oxford
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MVA-NP+M1 in people with Influenza, run by University of Oxford at 2 sites 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 10 inclusion and 23 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 11 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
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?
Safety of a new Influenza vaccine, MVA-NP+M1, when administered to healthy volunteers (time frame: 6 months). 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 NCT00993083, 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 11 Aug 2011.