InfluenzaPhase 1NCT00942071
A Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults
A Phase 1 study testing MVA-NP+M1 in people with Influenza, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This is an open label phase I study, to assess the safety of a novel influenza vaccine, MVA-NP+M1. All volunteers recruited will be healthy. Twelve volunteers will be administered with a single dose of 5 x 10^7 pfu of MVA-NP+M1 via the Intradermal (ID) route (group 1). 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?
- MVA-NP+M1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2008to Nov 2012
- 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
- Healthy adult aged 18 or over, no upper age limit
- Resident in or near Oxford for the duration of the vaccination study
- Able and willing (in the Investigators' opinions) to comply with all study requirements
- Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
- For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the duration of the study.
- Agreement to refrain from blood donation during the course of the study
- Written informed consent
Who cannot join
- Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
- Prior receipt of a recombinant MVA vaccine
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- 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 (inhaled and topical steroids are allowed)
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
- Any history of anaphylaxis in reaction to vaccination
Show all 15Show fewer
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- History of serious psychiatric condition
- Any chronic illness requiring ongoing or awaiting hospital specialist supervision, other than minor surgical procedures and follow up of surgery over 6 months prior to screening.
- Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
- Seropositive for hepatitis B surface antigen (HBsAg)
- Seropositive for hepatitis C virus (antibodies to HCV)
- For females, pregnancy, lactation or willingness/intention to become pregnant during the study
- 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, as determined by the investigators.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
About this study
Official title: A Phase I Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults
This is an open label phase I study, to assess the safety of a novel influenza vaccine, MVA-NP+M1. All volunteers recruited will be healthy. Twelve volunteers will be administered with a single dose of 5 x 10^7 pfu of MVA-NP+M1 via the Intradermal (ID) route (group 1). Sixteen volunteers will receive Intramuscular (IM) MVA-NP+M1. The first 8 volunteers will be administered a single dose of 5 x 10^7 pfu of MVA-NP+M1 followed by a further eight receiving 2.5 x 10^8 pfu of MVA-NP+M1 (group 2). The 3rd group will be split into 3 groups of 10 volunteers in the age ranges 50-59, 60-69 and 70 and above and administered intramuscularly with a single dose of 1.5 x 10^8 pfu of MVA-NP+M1. Safety data will be collected. The secondary aim of this study will be to assess the cellular immune responses generated by each dose.
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
- Intradermal injection at 5 x 10^7 pfu at day 0
MVA-NP+M1Biological
2.Intramuscular injection at 5 x 10^7 pfu/ml at day 0. Intramuscular injection at 2.5 x 10^8 pfu/ml at day 0
MVA-NP+M1Biological
3.Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0
| Study group | Role | What they receive |
|---|---|---|
| 1. MVA-NP+M1 ID | Experimental | 12 volunteers to receive MVA-NP+M1 via ID route Receives: Biological: MVA-NP+M1 |
| 2. MVA-NP+M1 IM | Experimental | 16 volunteers to receive MVA-NP+M1 via IM route Receives: Biological: MVA-NP+M1 |
| 3. MVA-NP+M1 IM upper age group | Experimental | 30 volunteers to receive MVA-NP+M1 via IM route Receives: Biological: MVA-NP+M1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of a new influenza vaccine, MVA-NP+M1, when administered to healthy volunteers.
Measured: 24 months
Secondary outcomes (1)
To assess the cellular immune response generated by a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2009 (estimated)
- Study startAug 2008
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Adrian VS Hill, D.Phil FRCP, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00942071
- Sponsor's protocol ID
- Flu001
- Status last verified
- Nov 2012
- First submitted
- 16 Jul 2009
- Last updated
- 29 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ferrara F, Del Rosario JMM, da Costa KAS, Kinsley R, Scott S, Fereidouni S, Thompson C, Kellam P, Gilbert S, Carnell G, Temperton N. Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies. Front Immunol. 2021 May 24;12:661379. doi: 10.3389/fimmu.2021.661379. eCollection 2021.
PubMed 34108964Antrobus RD, Lillie PJ, Berthoud TK, Spencer AJ, McLaren JE, Ladell K, Lambe T, Milicic A, Price DA, Hill AV, Gilbert SC. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One. 2012;7(10):e48322. doi: 10.1371/journal.pone.0048322. Epub 2012 Oct 31.
PubMed 23118984
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Safety and Immunogenicity of a New Influenza Vaccine Candidate MVA-NP+M1 in Healthy Adults
- ClinicalTrials.gov ID
- NCT00942071
- Acronym / sponsor ID
- Flu001
- Conditions
- Influenza
- Keywords
- Influenza, Vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- Aug 2008
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 20 Jul 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 an open label phase I study, to assess the safety of a novel influenza vaccine, MVA-NP+M1. All volunteers recruited will be healthy. Twelve volunteers will be administered with a single dose of 5 x 10^7 pfu of MVA-NP+M1 via the Intradermal (ID) route (group 1). Sixteen volunteers will receive Intramuscular (IM) MVA-NP+M1. The first 8 volunteers will be administered a single dose of 5 x 10^7 pfu of MVA-NP+M1 followed by a further eight receiving 2.5 x 10^8 pfu of MVA-NP+M1 (group 2). The 3rd group will be split into 3 groups of 10 volunteers in the age ranges 50-59, 60-69 and 70 and above and administered intramuscularly with a single dose of 1.5 x 10^8 pfu of MVA-NP+M1. Safety data will be collected. The secondary aim of this study will be to assess the cellular immune responses generated by each dose.
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
- 3
| Arm | Type | Receives |
|---|---|---|
| 1. MVA-NP+M1 ID | Experimental | Biological: MVA-NP+M112 volunteers to receive MVA-NP+M1 via ID route |
| 2. MVA-NP+M1 IM | Experimental | Biological: MVA-NP+M116 volunteers to receive MVA-NP+M1 via IM route |
| 3. MVA-NP+M1 IM upper age group | Experimental | Biological: MVA-NP+M130 volunteers to receive MVA-NP+M1 via IM route |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy adult aged 18 or over, no upper age limit
- Resident in or near Oxford for the duration of the vaccination study
- Able and willing (in the Investigators' opinions) to comply with all study requirements
- Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
- For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the duration of the study.
Key exclusion criteria (15 listed)
- Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
- Prior receipt of a recombinant MVA vaccine
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- 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 (inhaled and topical steroids are allowed)
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. 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+M11. Intradermal injection at 5 x 10^7 pfu at day 0 | Biological | 1. MVA-NP+M1 ID |
| MVA-NP+M12.Intramuscular injection at 5 x 10^7 pfu/ml at day 0. Intramuscular injection at 2.5 x 10^8 pfu/ml at day 0 | Biological | 2. MVA-NP+M1 IM |
| MVA-NP+M13.Intramuscular injection at 1.5 x 10^8 pfu/ml at day 0 | Biological | 3. MVA-NP+M1 IM upper age group |
Primary outcome
To assess the safety of a new influenza vaccine, MVA-NP+M1, when administered to healthy volunteers.
Time frame: 24 months
1 secondary outcome
To assess the cellular immune response generated by a new influenza vaccine, MVA-NP+M1, when administered as a single dose to healthy volunteers.
Time frame: 24 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 29 Nov 2012.
- Derived from this study: PubMed 34108964Ferrara F, Del Rosario JMM, da Costa KAS, Kinsley R, Scott S, Fereidouni S, Thompson C, Kellam P, Gilbert S, Carnell G, Temperton N. Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies. Front Immunol. 2021 May 24;12:661379. doi: 10.3389/fimmu.2021.661379. eCollection 2021.
- Derived from this study: PubMed 23118984Antrobus RD, Lillie PJ, Berthoud TK, Spencer AJ, McLaren JE, Ladell K, Lambe T, Milicic A, Price DA, Hill AV, Gilbert SC. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One. 2012;7(10):e48322. doi: 10.1371/journal.pone.0048322. Epub 2012 Oct 31.
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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, D.Phil FRCP principal investigator
University of Oxford
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 MVA-NP+M1 in people with Influenza, run by University of Oxford 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 15 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 29 Nov 2012. 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?
To assess the safety of a new influenza vaccine, MVA-NP+M1, when administered to healthy volunteers. (time frame: 24 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 NCT00942071, which also lists 2 linked publications.
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 29 Nov 2012.