TuberculosisPhase 1NCT00460590
Safety and Immunogenicity of MVA85A, in Healthy Volunteers in Cape Town
A Phase 1 study testing MVA 85A in people with Tuberculosis, run by University of Oxford at 1 site in South Africa.
Trial summary
This study is designed to evaluate the safety of MVA85A in healthy volunteers in Cape Town. We have shown that MVA85A is safe and immunogenic in both a mycobacterially naïve population in the UK and in a more mycobacterially exposed population in The Gambia. Read more about this study
- Who is it for?
- Ages 12 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- MVA 85A
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSouth Africa
- Study dates
- Oct 2005to Jun 2008
- 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 12 to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Healthy adults aged 18 to 50 years (for the first 2 arms)
- Healthy adolescents (aged 12-14) for the third arm of the study
- Screening Elispot negative (less than 17 spots/million PBMC) in all 3 ESAT6 pools and all 3 CFP10 pools
- Mantoux test <15mm (<10mm if BCG naïve)
- CXR normal with no evidence of active or past TB
- For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination
Show all 9Show fewer
- 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 >15mm
- 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. (For corticosteroids, this will mean prednisolone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- 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 diabetes mellitus
- Chronic or active neurological disease requiring ongoing specialist or medical supervision
- Chronic gastrointestinal disease requiring ongoing specialist or medical 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 or medical 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.
About this study
Official title: A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine MVA85A, in Healthy Volunteers With no Evidence of Infection With Mycobacterium Tuberculosis, in Cape Town
This study is designed to evaluate the safety of MVA85A in healthy volunteers in Cape Town. We have shown that MVA85A is safe and immunogenic in both a mycobacterially naïve population in the UK and in a more mycobacterially exposed population in The Gambia. The studies described here will be to assess the safety of MVA85A in 2 groups of adults, those with and without prior BCG vaccination. Once safety data has been obtained in these 2 groups, we will assess the safety of MVA85A in adolescents who have been previously vaccinated with BCG.
Read the detailed description
This is an open label Phase I safety study of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects with no evidence of infection with M.tb
Sample size:
This is an observational and descriptive safety study, 12 subjects with evidence of prior BCG vaccination and 12 adults with no evidence of prior BCG vaccination will be recruited and vaccinated with MVA85A. This sample size should allow determination of the magnitude of the outcome measures, especially of serious and severe adverse events rather than aiming to obtain statistical significance. Once three month follow-up of these two arms of the study is complete, we will recruit 12 adolescent school children (aged 12-14) and assess the safety and immunogenicity of a single immunisation with MVA85A in this group.
Rules for progression from adult studies to adolescents:
- No increased incidence in local and systemic side-effects compared with trials with MVA85A in Oxford and The Gambia. In the trials in the UK and The Gambia, all volunteers experience some mild local side-effects for 1-4 days after vaccination. Approximately two- thirds of volunteers experience some mild systemic side-effects in the first 24 hours after vaccination. These are self-limiting and all spontaneously resolve. These side-effects are consistent with data from use with other recombinant MVAs expressing other antigens (Moorthy VS et al, 2003).
- Immune responses measured 1 week after vaccination. We see strong immune responses 1 week after vaccination in the Oxford and Gambian volunteers (McShane et al, 2004). We do not know how long the responses in the South African volunteers will last for, but we would expect to see the induction of significant (compared with baseline) immune responses as measured by the ex-vivo Elispot assay, 1 week after vaccination
- Conditions
- Tuberculosis
- Being tested
- MVA 85A
- Keywords
- Tuberculosis, TB, MVA 85A
- 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
ID vaccine
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 12 adults with prior BCG Receives: Biological: MVA 85A |
| 2 | Experimental | 12 adults without prior BCG Receives: Biological: MVA 85A |
| 3 | Experimental | 12 Adolescents 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 of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (AEs).
Measured: year
Secondary outcomes (1)
To assess the immunogenicity of a single vaccination with MVA85A in healthy subjects. The specific endpoints for immunogenicity will be markers of cell-mediated immunity as outlined above
Measured: year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2007 (estimated)
- Study startOct 2005
- Primary completionJun 2008
- Study completionJun 2008
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 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
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cape Town
- Investigators
- Greg Hussey, Professor, Principal investigator, University Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00460590
- Sponsor's protocol ID
- TB008
- Status last verified
- Jun 2008
- First submitted
- 13 Apr 2007
- Last updated
- 7 Aug 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tanner R, Kakalacheva K, Miller E, Pathan AA, Chalk R, Sander CR, Scriba T, Tameris M, Hawkridge T, Mahomed H, Hussey G, Hanekom W, Checkley A, McShane H, Fletcher HA. Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC Infect Dis. 2014 Dec 3;14:660. doi: 10.1186/s12879-014-0660-7.
PubMed 25466778Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, Lang T, Veldsman A, Hatherill M, Merwe Lv, Fletcher HA, Mahomed H, Hill AV, Hanekom WA, Hussey GD, McShane H. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis. 2008 Aug 15;198(4):544-52. doi: 10.1086/590185.
PubMed 18582195
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine MVA85A, in Healthy Volunteers With no Evidence of Infection With Mycobacterium Tuberculosis, in Cape Town
- ClinicalTrials.gov ID
- NCT00460590
- Acronym / sponsor ID
- TB008
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, TB, MVA 85A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Cape Town
- Study start
- Oct 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 16 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.
This study is designed to evaluate the safety of MVA85A in healthy volunteers in Cape Town. We have shown that MVA85A is safe and immunogenic in both a mycobacterially naïve population in the UK and in a more mycobacterially exposed population in The Gambia. The studies described here will be to assess the safety of MVA85A in 2 groups of adults, those with and without prior BCG vaccination. Once safety data has been obtained in these 2 groups, we will assess the safety of MVA85A in adolescents who have been previously vaccinated with BCG.
Detailed description
This is an open label Phase I safety study of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects with no evidence of infection with M.tb
Sample size:
This is an observational and descriptive safety study, 12 subjects with evidence of prior BCG vaccination and 12 adults with no evidence of prior BCG vaccination will be recruited and vaccinated with MVA85A. This sample size should allow determination of the magnitude of the outcome measures, especially of serious and severe adverse events rather than aiming to obtain statistical significance. Once three month follow-up of these two arms of the study is complete, we will recruit 12 adolescent school children (aged 12-14) and assess the safety and immunogenicity of a single immunisation with MVA85A in this group.
Rules for progression from adult studies to adolescents:
- No increased incidence in local and systemic side-effects compared with trials with MVA85A in Oxford and The Gambia. In the trials in the UK and The Gambia, all volunteers experience some mild local side-effects for 1-4 days after vaccination. Approximately two- thirds of volunteers experience some mild systemic side-effects in the first 24 hours after vaccination. These are self-limiting and all spontaneously resolve. These side-effects are consistent with data from use with other recombinant MVAs expressing other antigens (Moorthy VS et al, 2003).
- Immune responses measured 1 week after vaccination. We see strong immune responses 1 week after vaccination in the Oxford and Gambian volunteers (McShane et al, 2004). We do not know how long the responses in the South African volunteers will last for, but we would expect to see the induction of significant (compared with baseline) immune responses as measured by the ex-vivo Elispot assay, 1 week after vaccination
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: MVA 85A12 adults with prior BCG |
| 2 | Experimental | Biological: MVA 85A12 adults without prior BCG |
| 3 | Experimental | Biological: MVA 85A12 Adolescents |
Who may qualify
- Ages
- 12 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Healthy adults aged 18 to 50 years (for the first 2 arms)
- Healthy adolescents (aged 12-14) for the third arm of the study
- Screening Elispot negative (less than 17 spots/million PBMC) in all 3 ESAT6 pools and all 3 CFP10 pools
- Mantoux test <15mm (<10mm if BCG naïve)
- CXR normal with no evidence of active or past TB
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 >15mm
- 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. (For corticosteroids, this will mean prednisolone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
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 85AID vaccine | Biological | 1, 2, 3 |
Primary outcome
To assess the safety of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (AEs).
Time frame: year
1 secondary outcome
To assess the immunogenicity of a single vaccination with MVA85A in healthy subjects. The specific endpoints for immunogenicity will be markers of cell-mediated immunity as outlined above
Time frame: 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 7 Aug 2008.
- Derived from this study: PubMed 25466778Tanner R, Kakalacheva K, Miller E, Pathan AA, Chalk R, Sander CR, Scriba T, Tameris M, Hawkridge T, Mahomed H, Hussey G, Hanekom W, Checkley A, McShane H, Fletcher HA. Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC Infect Dis. 2014 Dec 3;14:660. doi: 10.1186/s12879-014-0660-7.
- Derived from this study: PubMed 18582195Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, Lang T, Veldsman A, Hatherill M, Merwe Lv, Fletcher HA, Mahomed H, Hill AV, Hanekom WA, Hussey GD, McShane H. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis. 2008 Aug 15;198(4):544-52. doi: 10.1086/590185.
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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.
Greg Hussey, Professor principal investigator
University Cape Town
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 South Africa.
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 7 Aug 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 South Africa. 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 single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (AEs). (time frame: year). 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 NCT00460590, 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 7 Aug 2008.