TuberculosisPhase 1NCT00653770
A Phase I Study to Assess the Safety and Immunogenicity of Tuberculosis (TB) Vaccine Candidates FP85A and MVA85A
A Phase 1 study testing FP85A and MVA85A in people with Tuberculosis, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This is a Phase I study whose primary outcome is to assess the safety of a new tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- FP85A and MVA85A
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2007to Jan 2010
- 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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult aged 18 to 50 years
- Resident in or near Oxford for the duration of the vaccination study
- Immunization with BCG greater than 12 months prior to enrolment in the 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
- Agreement to practice barrier contraception from the start of the study until 3 months after the final vaccination
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- For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the entire 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 or fowlpox 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
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- Close contact with fowl during the study period (e.g. chicken farming)
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- History of serious 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)
- 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.
- Mantoux skin test equal to or greater than 15 millimetres
- Screening Elispot positive (greater than 17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide pool
- Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study to Assess the Safety and Immunogenicity of New TB Vaccine Candidates FP85A and MVA85A, in Healthy Adults Who Have Previously Been Immunized With BCG, Using a Prime-boost Delivery Schedule
This is a Phase I study whose primary outcome is to assess the safety of a new tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG. The secondary outcome is to assess the cellular immune response in the same population. The trial consists of 36 subjects in 3 groups. The first group will be vaccinated with FP85A alone, the second group will be vaccinated with MVA85A followed by FP85A 28 days later and the third group will be vaccinated with FP85A followed by MVA85A 28 days later.
Read the detailed description
Recombinant fowlpox virus as a vector
Fowlpox virus is only infectious to avian species, but it is able to express antigens in mammalian cells and induce protective immune responses, making it a suitable candidate vector. Recombinant fowlpox viruses have been developed that express antigens from tumour cells, HIV and malaria. FP9 is a live, highly attenuated form of a European strain of fowlpox virus. It was derived from multiple passages in avian cells, followed by plaque purification and the genome has been fully characterised. Fowlpox virus was initially used as a recombinant avian vaccine, but it has also been shown to be a potent inducer of CD8+T cells in preclinical mammalian models and in human trials . In fact, FP9 was found to be more immunogenic than wild type fowlpox and, when used with recombinant MVA in a prime boost regime induced a protective immune response against Plasmodium berghi.
Clinical experience with recombinant fowlpox viruses in Oxford Three FP vaccines encoding different malaria antigens have been used so far in clinical trials in Oxford, FP9 ME-TRAP, FP9 CS and FP9 PP. To date 87 doses of FP9 ME-TRAP have been given to 55 volunteers in Oxford using various regimens in combination with DNA as well as recombinant MVA vaccines. The local and systemic safety profile of FP9 ME-TRAP is comparable to that described for recombinant MVA vaccines. No vaccine-related serious adverse events have been observed. Pain and erythema at the injection site are the predominant local side effects, with the erythema being maximal within 2 to 3 days post-vaccination before receding. The commonest systemic side effect after FP9 ME-TRAP is of feeling feverish although this is not always associated with a documented fever. Other solicited side effects are myalgia, arthralgia, headache and nausea. FP9 CS has been used recently in a phase I study in 25 healthy volunteers in Oxford, at doses of 1x10^8 pfu. Analysis of safety and tolerability suggests similar side effect profile to FP9 ME-TRAP. No serious adverse events were noted in the study. In a phase I/IIa study which is nearing completion, 15 volunteers were immunised with 5x10^7 pfu of FP9 PP, with no vaccine-related serious adverse events and comparable adverse events.
- Conditions
- Tuberculosis
- Being tested
- FP85A, MVA85A
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FP85ABiological
Recombinant Fowlpox virus 9 expressing antigen 85A from M. tuberculosis (5 x10^7 pfu)
MVA85ABiological
Modified vaccinia virus Ankara expressing antigen 85A from M. tuberculosis (5 x 10^7 pfu)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | FP85A at day 0 Receives: Biological: FP85A |
| 2 | Experimental | MVA85A at day 0 and FP85A at day 28 Receives: Biological: FP85A; Biological: MVA85A |
| 3 | Experimental | FP85A at day 0 and MVA85A at day 28 Receives: Biological: FP85A; Biological: MVA85A |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of a new tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG
Measured: 3 months
Secondary outcomes (1)
To assess the cellular immune response generated by FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime to healthy volunteers, who have previously been vaccinated with BCG.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2008 (estimated)
- Study startSep 2007
- Primary completionJan 2010
- Study completionJan 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 TuberculosisStudies 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Investigators
- Helen McShane, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00653770
- Sponsor's protocol ID
- TB017
- Status last verified
- Feb 2010
- First submitted
- 2 Apr 2008
- Last updated
- 9 Feb 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rowland R, Pathan AA, Satti I, Poulton ID, Matsumiya MM, Whittaker M, Minassian AM, O'Hara GA, Hamill M, Scott JT, Harris SA, Poyntz HC, Bateman C, Meyer J, Williams N, Gilbert SC, Lawrie AM, Hill AV, McShane H. Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial. Hum Vaccin Immunother. 2013 Jan;9(1):50-62. doi: 10.4161/hv.22464. Epub 2012 Nov 10.
PubMed 23143773
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2010. 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 New TB Vaccine Candidates FP85A and MVA85A, in Healthy Adults Who Have Previously Been Immunized With BCG, Using a Prime-boost Delivery Schedule
- ClinicalTrials.gov ID
- NCT00653770
- Acronym / sponsor ID
- TB017
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 7 Apr 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.
This is a Phase I study whose primary outcome is to assess the safety of a new tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG. The secondary outcome is to assess the cellular immune response in the same population. The trial consists of 36 subjects in 3 groups. The first group will be vaccinated with FP85A alone, the second group will be vaccinated with MVA85A followed by FP85A 28 days later and the third group will be vaccinated with FP85A followed by MVA85A 28 days later.
Detailed description
Recombinant fowlpox virus as a vector
Fowlpox virus is only infectious to avian species, but it is able to express antigens in mammalian cells and induce protective immune responses, making it a suitable candidate vector. Recombinant fowlpox viruses have been developed that express antigens from tumour cells, HIV and malaria. FP9 is a live, highly attenuated form of a European strain of fowlpox virus. It was derived from multiple passages in avian cells, followed by plaque purification and the genome has been fully characterised. Fowlpox virus was initially used as a recombinant avian vaccine, but it has also been shown to be a potent inducer of CD8+T cells in preclinical mammalian models and in human trials . In fact, FP9 was found to be more immunogenic than wild type fowlpox and, when used with recombinant MVA in a prime boost regime induced a protective immune response against Plasmodium berghi.
Clinical experience with recombinant fowlpox viruses in Oxford Three FP vaccines encoding different malaria antigens have been used so far in clinical trials in Oxford, FP9 ME-TRAP, FP9 CS and FP9 PP. To date 87 doses of FP9 ME-TRAP have been given to 55 volunteers in Oxford using various regimens in combination with DNA as well as recombinant MVA vaccines. The local and systemic safety profile of FP9 ME-TRAP is comparable to that described for recombinant MVA vaccines. No vaccine-related serious adverse events have been observed. Pain and erythema at the injection site are the predominant local side effects, with the erythema being maximal within 2 to 3 days post-vaccination before receding. The commonest systemic side effect after FP9 ME-TRAP is of feeling feverish although this is not always associated with a documented fever. Other solicited side effects are myalgia, arthralgia, headache and nausea. FP9 CS has been used recently in a phase I study in 25 healthy volunteers in Oxford, at doses of 1x10^8 pfu. Analysis of safety and tolerability suggests similar side effect profile to FP9 ME-TRAP. No serious adverse events were noted in the study. In a phase I/IIa study which is nearing completion, 15 volunteers were immunised with 5x10^7 pfu of FP9 PP, with no vaccine-related serious adverse events and comparable adverse events.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: FP85AFP85A at day 0 |
| 2 | Experimental | Biological: FP85A, Biological: MVA85AMVA85A at day 0 and FP85A at day 28 |
| 3 | Experimental | Biological: FP85A, Biological: MVA85AFP85A at day 0 and MVA85A at day 28 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy adult aged 18 to 50 years
- Resident in or near Oxford for the duration of the vaccination study
- Immunization with BCG greater than 12 months prior to enrolment in the 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
Key exclusion criteria (18 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 or fowlpox 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 |
|---|---|---|
| FP85ARecombinant Fowlpox virus 9 expressing antigen 85A from M. tuberculosis (5 x10^7 pfu) | Biological | 1, 2, 3 |
| MVA85AModified vaccinia virus Ankara expressing antigen 85A from M. tuberculosis (5 x 10^7 pfu) | Biological | 2, 3 |
Primary outcome
To assess the safety of a new tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG
Time frame: 3 months
1 secondary outcome
To assess the cellular immune response generated by FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime to healthy volunteers, who have previously been vaccinated with BCG.
Time frame: 12 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 9 Feb 2010.
- Derived from this study: PubMed 23143773Rowland R, Pathan AA, Satti I, Poulton ID, Matsumiya MM, Whittaker M, Minassian AM, O'Hara GA, Hamill M, Scott JT, Harris SA, Poyntz HC, Bateman C, Meyer J, Williams N, Gilbert SC, Lawrie AM, Hill AV, McShane H. Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial. Hum Vaccin Immunother. 2013 Jan;9(1):50-62. doi: 10.4161/hv.22464. Epub 2012 Nov 10.
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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.
Helen McShane 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 FP85A and MVA85A in people with Tuberculosis, 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 9 inclusion and 18 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 9 Feb 2010. 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 tuberculosis vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost regime, to healthy volunteers, who have previously been vaccinated with BCG (time frame: 3 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 NCT00653770, 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 9 Feb 2010.