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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University of Oxford
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- The occurance and severity of local and systemic side effects will be monitored. Vital signs and local reactions will be monitored at 30 and 60 minutes after each mmunisation (and after 7 days).
Study Overview
Brief Summary
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.
Detailed Description
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.
- 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
- Inclusion Criteria
- Healthy adult aged 18-55 years.
- Normal medical history and physical examination.
- Normal urine dipstick, blood count, liver enzymes, and creatinine.
- Exclusion Criteria
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy adult aged 18-55 years.
- •Normal medical history and physical examination.
- •Normal urine dipstick, blood count, liver enzymes, and creatinine.
Exclusion Criteria
- •Exposure to TB/BCG vaccination at any point. Previous residence in a TB endemic area.
- •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.
- •Oral or systemic steroid medication or the use of immunosuppressive agents.
- •Positive HIV antibody test, HCV antibody test or positive HBV serology except post-vaccination.
- •Heaf test greater than Grade 0
- •Confirmed pregnancy
- •Previous MVA immunisations
Outcomes
Primary Outcomes
The occurance and severity of local and systemic side effects will be monitored. Vital signs and local reactions will be monitored at 30 and 60 minutes after each mmunisation (and after 7 days).
Blood will be taken at: the screening visit, prior to the BCG vaccination, 1 and 4 weeks after the BCG vaccination, and also at 1,4, 8, 12 and 24 weeks after the MVA85A vaccination.
Secondary Outcomes
- Immunogenicity will be measured: The induction of T cell responses (as measured by an interferon-gamma Elispot assay) will be performed on PBMCs from blood samples taken at the specified time points.
- Proliferation assays and cytotoxic T cell assays will be performed. Other serological measures of immune response, i.e. antibody titres will be analysed on frozen plasma samples.