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.
This study is to assesss the safety and immunogenicity of vaccine based on Modified Vaccinia Ankara (MVA) expressing the 85A antigen (from Mycobacterium. tuberculosis). This vaccine is delivered intrdermally by a needle injection in healthy volunteers.
1. This is a phase I study to assesss the safety and immunogenicity a recombinant MVA
encoding a secreted antigen from Mycobacterium. tuberculosis Antigen 85A, delivered
intrdermally by a needle injection in healthy BCG naive volunteers.
2. 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.
3. 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
4. Inclusion Criteria
- Healthy adult aged 18-45 years.
- Normal medical history and physical examination.
- Normal urine dipstick, blood count, liver enzymes, and creatinine.
5. 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. Positive Heaf test
6. Confirmed pregnancy
7. Previous MVA immunisations
6. 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
7 Immunisation
On Day 0 and Day 21, subjects will receive a single intradermal injection of 5 x
107pfu in 0.1ml over the deltoid muscle. Subjects will be observed for an hour
after all immunisations. 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 first vaccination, *1 week after the first vaccination, prior to the second
vaccination, *1 week after the second vaccination, 4 weeks, 8 weeks, *12 weeks and
24 weeks after the second 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 on screening and each
vaccination day 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.
At the end of the six month follow-up period, volunteers will be offered BCG
immunisation. If they accept, imunological monitering will continue for a further
six months. 50mls of blood will be taken for cellular immunological assays 1 week,
2 weeks, 1 month, 2 months, 3 months and 6 months after BCG immunisation.
All blood tests will be taken within 1-3 days of the due date as described in the
schedule above.
8 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.
This study has been completed.
;
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
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