TuberculosisPhase 1NCT00465465
A Study of 2 Doses of a New TB Vaccine, MVA85A, in Healthy Volunteers Previously Vaccinated With BCG
A Phase 1 study testing MVA 85A in people with Tuberculosis, run by University of Oxford at 1 site in United Kingdom.
Trial summary
The dose of recombinant MVA used in the TB trials to date is relatively low compared with other trials using recombinant MVAs which have used up to 2.5 x 108pfu (A Hill, personal communication). 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?
- MVA 85A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2005to Sep 2007
- 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 adults aged 18 to 50 years
- Resident in or near Oxford for the duration of the vaccination study
- Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's GP
- Screening Elispot negative (less than 10 sfc/million PBMC) for all 3 ESAT6 peptide pools and all 3 CFP10 peptide pools
- Mantoux test not greater than 15 millimetres
- For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination
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- Agreement to refrain from blood donation during the course of the study
- Written informed consent
- Willingness to undergo an HIV test
Who cannot join
- Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix I
- Mantoux greater than 15 millimetres
- Prior receipt of a recombinant MVA or Fowlpox vaccine
- Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
- Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia
Show all 25Show fewer
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
- Evidence of cardiovascular disease
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- History of insulin requiring diabetes mellitus
- Chronic or active neurological disease requiring ongoing specialist supervision
- Chronic gastrointestinal disease requiring ongoing specialist supervision
- History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
- Suspected or known current 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)
- Evidence of serious psychiatric condition
- Any other on-going chronic illness requiring hospital specialist supervision
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- Pregnant or lactating female
- Female who is willing or intends to become pregnant during the study
- Any history of anaphylaxis in reaction to vaccination
- Inability to give informed consent
- PI assessment of lack of willingness to participate and comply with all requirements of the protocol
- Any other finding which in the opinion of the investigator would significantly increase the risk of having an adverse outcome from participating in this protocol
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Oxford, CCVTM, Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
About this study
Official title: A Dose Selection Study Evaluating the Safety and Immunogenicity of 2 Different Doses of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Have Previously Been Vaccinated With BCG
The dose of recombinant MVA used in the TB trials to date is relatively low compared with other trials using recombinant MVAs which have used up to 2.5 x 108pfu (A Hill, personal communication). Having demonstrated safety and immunogenicity of 5 x 107pfu of MVA85A, we now need to perform a dose optimization study, prior to commencing larger scale Phase II and III studies in South Africa. We will vaccinate 12 volunteers with a dose half a log lower than the dose we are currently using, i.e. 107pfu MVA85A, and 12 volunteers with a dose half a log higher, i.e. 108pfu.
Read the detailed description
MVA85A (at a dose of 5 x 107pfu) has been administered to 41 healthy volunteers in the UK and 17 healthy volunteers in The Gambia, with no serious adverse events. We have designed our Phase I studies to allow for a vaccination of volunteer groups sequentially with a step-wise increase in mycobacterial exposure, in order to minimize the possibility of a Koch reaction. A Koch reaction describes the development of immunopathology in a person or animal with tuberculosis, when an exaggerated immune response to M.tb is stimulated. It was described in patients with TB disease when Koch performed his original studies employing mycobacteria as a type of therapeutic vaccination. It has now been demonstrated in the mouse model of therapeutic vaccination (Taylor, 2003). Available animal data suggest that these reactions do not occur in mice latently infected with M.tb, suggesting that such reactions may correlate with high bacterial load and that the Koch phenomenon may not pose a problem for vaccination of healthy albeit latently infected humans. We started these studies in healthy volunteers who were as mycobacterially naïve as possible. They were skin test negative and Elispot negative for PPD, ESAT 6 and CFP10, and had not had previously been vaccinated with BCG. We have now completed studies in the UK vaccinating volunteers previously vaccinated with BCG (McShane, 2004). These volunteers are excluded if their Mantoux test is greater than 15 millimeters. These studies are ongoing in The Gambia. The group we are currently recruiting for on this increasing mycobacterial spectrum are healthy volunteers who are latently infected with M.tb.
Decision matrix for selecting MVA85A dose
- If reducing the dose of MVA85A results in reduced immunogenicity, we could use either the 5x107 or 108 dose, and would select the lower of these on the grounds of safety.
- If increasing the dose of MVA85A increases the incidence of side-effects, we could use either the 5x107 or 107 dose, and we would use the higher of these on the grounds of immunogenicity.
- If increasing the dose of MVA85A results in increased immunogenicity and no increase in side-effects, we could use either the 5x107 or 108 dose in subsequent trials
- If reducing the dose of MVA85A results in no reduction in immunogenicity we could use either the 107 or 5x107 dose in subsequent trials
- If all three doses are equally safe and immunogenic we will use either the low or 5x107 dose.
- Conditions
- Tuberculosis
- Being tested
- MVA 85A
- Keywords
- Tuberculosis, TB, MVA 85A, BCG
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVA 85ABiological
i.d. injection
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Dose of 1 x 10^7 Receives: Biological: MVA 85A |
| 2 | Active comparator | Dose of 1 x 10^8 Receives: Biological: MVA 85A |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and immunogenicity of 2 different doses of intradermal vaccination of MVA85A, 10^7pfu and 10^8pfu, when administered to healthy subjects who have previously been vaccinated with BCG
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2007 (estimated)
- Study startOct 2005
- Primary completionSep 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 24 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
- NCT00465465
- Sponsor's protocol ID
- TB009
- Status last verified
- Mar 2008
- First submitted
- 24 Apr 2007
- Last updated
- 4 Apr 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Selection Study Evaluating the Safety and Immunogenicity of 2 Different Doses of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Have Previously Been Vaccinated With BCG
- ClinicalTrials.gov ID
- NCT00465465
- Acronym / sponsor ID
- TB009
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, TB, MVA 85A, BCG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Oct 2005
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 25 Apr 2007 (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.
The dose of recombinant MVA used in the TB trials to date is relatively low compared with other trials using recombinant MVAs which have used up to 2.5 x 108pfu (A Hill, personal communication). Having demonstrated safety and immunogenicity of 5 x 107pfu of MVA85A, we now need to perform a dose optimization study, prior to commencing larger scale Phase II and III studies in South Africa. We will vaccinate 12 volunteers with a dose half a log lower than the dose we are currently using, i.e. 107pfu MVA85A, and 12 volunteers with a dose half a log higher, i.e. 108pfu.
Detailed description
MVA85A (at a dose of 5 x 107pfu) has been administered to 41 healthy volunteers in the UK and 17 healthy volunteers in The Gambia, with no serious adverse events. We have designed our Phase I studies to allow for a vaccination of volunteer groups sequentially with a step-wise increase in mycobacterial exposure, in order to minimize the possibility of a Koch reaction. A Koch reaction describes the development of immunopathology in a person or animal with tuberculosis, when an exaggerated immune response to M.tb is stimulated. It was described in patients with TB disease when Koch performed his original studies employing mycobacteria as a type of therapeutic vaccination. It has now been demonstrated in the mouse model of therapeutic vaccination (Taylor, 2003). Available animal data suggest that these reactions do not occur in mice latently infected with M.tb, suggesting that such reactions may correlate with high bacterial load and that the Koch phenomenon may not pose a problem for vaccination of healthy albeit latently infected humans. We started these studies in healthy volunteers who were as mycobacterially naïve as possible. They were skin test negative and Elispot negative for PPD, ESAT 6 and CFP10, and had not had previously been vaccinated with BCG. We have now completed studies in the UK vaccinating volunteers previously vaccinated with BCG (McShane, 2004). These volunteers are excluded if their Mantoux test is greater than 15 millimeters. These studies are ongoing in The Gambia. The group we are currently recruiting for on this increasing mycobacterial spectrum are healthy volunteers who are latently infected with M.tb.
Decision matrix for selecting MVA85A dose
- If reducing the dose of MVA85A results in reduced immunogenicity, we could use either the 5x107 or 108 dose, and would select the lower of these on the grounds of safety.
- If increasing the dose of MVA85A increases the incidence of side-effects, we could use either the 5x107 or 107 dose, and we would use the higher of these on the grounds of immunogenicity.
- If increasing the dose of MVA85A results in increased immunogenicity and no increase in side-effects, we could use either the 5x107 or 108 dose in subsequent trials
- If reducing the dose of MVA85A results in no reduction in immunogenicity we could use either the 107 or 5x107 dose in subsequent trials
- If all three doses are equally safe and immunogenic we will use either the low or 5x107 dose.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Biological: MVA 85ADose of 1 x 10^7 |
| 2 | Active comparator | Biological: MVA 85ADose of 1 x 10^8 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy adults aged 18 to 50 years
- Resident in or near Oxford for the duration of the vaccination study
- Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's GP
- Screening Elispot negative (less than 10 sfc/million PBMC) for all 3 ESAT6 peptide pools and all 3 CFP10 peptide pools
- Mantoux test not greater than 15 millimetres
Key exclusion criteria (25 listed)
- Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix I
- Mantoux greater than 15 millimetres
- Prior receipt of a recombinant MVA or Fowlpox vaccine
- Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
- Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination.
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 85Ai.d. injection | Biological | 1, 2 |
Primary outcome
To assess the safety and immunogenicity of 2 different doses of intradermal vaccination of MVA85A, 10^7pfu and 10^8pfu, when administered to healthy subjects who have previously been vaccinated with BCG
Time frame: 1 year
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 4 Apr 2008.
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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 MVA 85A 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 25 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 4 Apr 2008. 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 and immunogenicity of 2 different doses of intradermal vaccination of MVA85A, 10^7pfu and 10^8pfu, when administered to healthy subjects who have previously been vaccinated with BCG (time frame: 1 year). 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 4 Apr 2008.