Plain English Summary
Background and study aims
Tuberculosis (TB) is a highly contagious bacterial infection. It is generally spread by breathing in tiny droplets released into the air by an infected person coughing or sneezing. TB usually affects the lungs, but it can also affect other areas of the body such as the bones, brain and kidneys. It is particularly common in third world countries and an infection can be devastating if it is not treated. MVA85A is a new vaccine which has been developed to prevent people from catching TB (immunise). The aim of this study is to investigate the safety and the effectiveness as a vaccine (immunogenicity) of this vaccine in healthy adults and adolescents.
Who can participate?
Healthy adults aged between 18 and 50 and healthy adolescents aged between 12 and 14 living in Cape Town (Africa), who have tested negative for TB.
What does the study involve?
All participants receive a single intradermal injection (injection into the lower layer of skin) of the MVA85A TB vaccine. After one year, all participants are followed up and have a blood test in order to find out if there are chemical indicators (biomarkers) suggesting that they have become immune to TB. Participants are also monitored to see if they show any signs of undesirable side-effects to the vaccine.
What are the possible benefits and risks of participating?
There are no direct benefits of participating, however participants are able to receive information about their general health. There is a risk of pain and bruising when blood is taken and during injections, as well as common complications of the vaccination (mild to moderate discomfort at the site of vaccination) and uncommon complications, which include headache, fever and soreness and itching at the site of the injection.
Where is the study run from?
Brewelskloof Hospital, Worcester, Western Cape Province (South Africa)
When is the study starting and how long is it expected to run for?
August 2005 to May 2008
Who is funding the study?
Wellcome Trust (UK) (Grant reference: 081122)
Who is the main contact?
Dr Helen McShane
helen.mcshane@ndm.ox.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Helen McShane
ORCID ID
http://orcid.org/0000-0002-2126-5142
Contact details
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
University of Oxford
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom
+44 1865 857417
helen.mcshane@ndm.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00460590
Protocol/serial number
TB008; 081122
Study information
Scientific 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
Acronym
Study hypothesis
To assess the safety and immunogenicity of a new TB vaccine (MVA85A) in healthy adults and adolescents in South Africa.
This is an observational and descriptive safety study. 12 subjects with evidence of prior Bacille Calmette-Guerin (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 and immunology, 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 years) and assess the safety and immunogenicity of a single immunisation with MVA85A in this group.
Ethics approval
1. The Oxford Tropical Research Ethics Committee on the 24th March 2005 (ref: 05/Q1604/12)
2. The University of Cape Town Research Ethics Committee on the 30th May 2005 (ref: 383/2004)
Study design
A single site open label phase I safety study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Tuberculosis
Intervention
MVA85A is a modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. All subjects will receive a single intradermal vaccination of 5x10^7 pfu (plaque forming units) of MVA85A. There is no control group.
Follow up is for 12 months.
Intervention type
Drug
Phase
Phase I
Drug names
MVA85A tuberculosis vaccine
Primary outcome measure
The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (AEs) at follow up visits up to a year post-vaccination.
Secondary outcome measures
The specific endpoints for immunogenicity will be markers of cell-mediated immunity (e.g. gamma interferon [IFN-g], tumour necrotising facto alpha [TNF-a], etc) at follow up visits up to a year post-vaccination.
Overall trial start date
01/08/2005
Overall trial end date
31/05/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Healthy adults aged 18 to 50 years (for the first 2 arms), either sex
2. Healthy adolescents (aged 12 - 14) for the third arm of the study, either sex
3. Screening Elispot negative (less than 17 spots/million PBMC) in all three ESAT6 pools and all three CFP10 pools
4. Mantoux test less than 15 mm (less than 10 mm if BCG negative)
5. Chest x-ray (CXR) normal with no evidence of active or past TB
6. For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination
7. Agreement to refrain from blood donation during the course of the study
8. Written informed consent
9. Willingness to undergo a human immunodeficiency virus (HIV) test
Participant type
Patient
Age group
Other
Gender
Both
Target number of participants
24 adults and 12 adolescents = 36 total
Participant exclusion criteria
1. Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
2. Mantoux greater than 15 mm
3. Prior receipt of a recombinant MVA or Fowlpox vaccine
4. 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
5. 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).
6. Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and asplenia
7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
8. Evidence of cardiovascular disease
9. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
10. History of diabetes mellitus
11. Chronic or active neurological disease requiring ongoing specialist or medical supervision
12. Chronic gastrointestinal disease requiring ongoing specialist or medical supervision
13. History of greater than two hospitalisations for invasive bacterial infections (pneumonia, meningitis)
14. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
15. Seropositive for hepatitis B surface antigen (HBsAg)
16. Seropositive for hepatitis C virus (antibodies to HCV)
17. Evidence of serious psychiatric condition
18. Any other ongoing chronic illness requiring hospital specialist or medical supervision
19. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
20. Pregnant or lactating female
21. Female who is willing or intends to become pregnant during the study
22. Any history of anaphylaxis in reaction to vaccination
23. Inability to give informed consent
24. PI assessment of lack of willingness to participate and comply with all requirements of the protocol
25. 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
Recruitment start date
15/09/2005
Recruitment end date
22/05/2008
Locations
Countries of recruitment
South Africa
Trial participating centre
Brewelskloof Hospital, Worcester
Haarlem Street
Worcester
6850
South Africa
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) - Technology Transfer Division (TTD) award (grant ref: 081122)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Available on request
Basic results (scientific)
Publication list
2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18582195
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20017188
Publication citations
-
Results
Hawkridge 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, 198, 4, 544-552, doi: 10.1086/590185.