Tuberculosis Clinical Trial
Official title:
A Phase I Study of the Safety and Immunogenicity of a Recombinant MVA Vaccine Encoding a Secreted Antigen From M. Tuberculosis, Antigen 85A, Delivered Intradermally by a Needle Injection in Healthy Volunteers Who Have Received BCG Immunisation 1 Month Previously
This is a phase I study to test the immunogenicity of a recombinant vaccine based on Modified Vaccinia Ankara (MVA) expressing the antigen 85A (from Mycobacterium tuberculosis). This vaccine is delivered intradermally by a needle injection in healthy volunteers previously vaccinated with BCG.
This is a phase I study to test the immunogenicity of a recombinant vaccine based on
Modified Vaccinia Ankara (MVA) expressing the antigen 85A (from Mycobacterium tuberculosis).
This vaccine is delivered intradermally by a needle injection in healthy volunteers who have
recieved a BCG immunisation month previously.
1. Selection of volunteers
Volunteers for the study will be recruited through advertisements. Each volunteer will
have received an information sheet concerning the study and will have agreed to
participate in writing. Volunteers will be given at least 48 hours between reading the
information leaflet and agreeing to participate. Female volunteers will be told of the
theoretical risk of congenital anomaly should they become pregnant during the study and
only those who undertake to take precautions to avoid pregnancy during the study period
will be eligible. Volunteers will give signed consent for their GP’s to be notified
about their participation in the trial. The GP will be faxed a letter on the day of
screening and asked to reply if they know of a reason why the volunteer should not take
part. The signed consent form will also be faxed with the letter.
2. Screening
Volunteers will be asked to sign the informed consent form for screening. The following
will be performed:
- Medical history and examination
- Laboratory evaluations – including clinical chemistry, haematology, HLA typing,
anti-vaccinia antibodies, anti-HBV antibodies, anti-HCV antibodies, anti-HIV
antibodies
- Heaf test – to exclude prior exposure to TB
- Urinalysis and urine pregnancy test if female
3. Inclusion Criteria
- Healthy adult aged 18-55 years.
- Normal medical history and physical examination.
- Normal urine dipstick, blood count, liver enzymes, and creatinine.
4. Exclusion Criteria
1. Exposure to TB/BCG vaccination at any point. Previous residence in a TB endemic
area.
2. Clinically significant history of skin disorder (eczema, psoriasis, etc.),
allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine
disorder, liver disease, renal disease, gastrointestinal disease, neurological
illness, psychiatric disorder, drug or alcohol abuse.
3. Oral or systemic steroid medication or the use of immunosuppressive agents.
4. Positive HIV antibody test, HCV antibody test or positive HBV serology except
post-vaccination.
5. Heaf test greater than Grade 0
6. Confirmed pregnancy
7. Previous MVA immunisations
5. Withdrawal Criteria
1. Withdrawal of consent by subject for any reason
2. Loss to follow-up
3. Non-compliance with study procedures
4. Protocol violation
5. Serious adverse event (as defined in Appendix 3)
6. Any other reason at discretion of the Principal Investigator
7. Confirmed pregnancy during study period
6. Immunisation
On Day 0, subjects will receive a single intradermal injection of 0.1ml BCG (SSI
strain) over the deltoid muscle. Blood will be taken at 2 weeks and 4 weeks after this
immunisation. At 4 weeks, after blood has been taken, volunteers will be immunised with
5 x 107pfu MVA85A in 0.1ml. Subjects will be observed for an hour after MVA85A
immunisation. Vital signs will be monitored at 30 and 60 minutes post-immunisation.
Local reactions at the site of administration will be evaluated at 60 minutes.
A photograph of the injection site may be taken at 48 hours (with written consent). The
injection site will be reviewed 7 days after each immunization.
Blood will be taken at the following time points: At the screening visit*, prior to the
BCG vaccination, 2 weeks and 4 weeks after BCG, *1 week after the MVA85A vaccination, 2
weeks, 4 weeks, *8 weeks, and *24 weeks after the vaccination. Up to 55 mls will be
taken at any one time with the total being no more than 500 mls over the study period.
*Samples taken on these dates will be tested for full blood count and biochemical
screen. Immunological assays will be performed at all time points to determine vaccine
immunogenicity. A pregnancy test will be performed prior to vaccination for female
volunteers. Peripheral blood mononuclear cells will be prepared for cellular
immunological assays to be performed without or following cryopreservation. Other
serological measures of immune response, i.e. antibody titres, will be assayed on
frozen plasma samples.
All blood tests will be taken within 1-3 days of the due date as described in the
schedule above.
7. Endpoints
The occurance and severity of local side-effects The occurance and severity of systemic
side-effects The induction of T cell responses (as measured by an interferon-gamma Elispot
assay).
Proliferation assays and cytotoxic T cell assays will be performed on strong CD4+ and CD8+
responses respectively.
;
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
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