A BCG Challenge Model Study to Assess Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the BCG 'challenge' model a four-arm study design has been chosen. Twelve subjects will be recruited into each arm of the study. Allocation of BCG-naïve volunteers to either group A or B, and BCG-vaccinated volunteers to either group C or D, will be performed on a one-to-one alternating basis. Subjects in each group will be challenged by BCG administered intradermally. Prior to challenge, pre-existing immunity to TB will be induced by vaccination with BCG, MVA85A, and both in combination (when compared to BCG- & MVA85A-naïve individuals). BCG quantification will be assessed by analysing the tissue obtained in a punch biopsy of volunteers' skin over the site of BCG 'challenge' vaccination. Any reduction in BCG quantification between groups will then be correlated to existing (and future) laboratory assays of vaccine-induced immune responses in order to identify potential immunological correlates of protection.

Official Title
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A Phase 1 Study to Evaluate a BCG Challenge Model as a Method of Assessing Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A, Alone and in Combination

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: BCG: 100 microlitres   2-8 x 105 pfu
* Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres   2-8 x 105 pfu


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult aged 18-55 years Resident in or near Oxford for the duration of the study period No relevant findings in medical history or on physical examination Willingness to allow the Investigators to discuss the individual's medical history with their GP Willingness to use effective contraception for the duration of the study period (females only) Agreement to refrain from blood donation during the course of the study Willingness to give written informed consent Agreement to allow the Investigator to register volunteer details with a confidential database to prevent concurrent entry into clinical trials Able and willing (in the Investigator's opinion) to comply with all the study requirements Additional criteria to be met for subjects in group A: None Additional criteria to be met for subjects in group B: Willingness to use continuous effective barrier contraception for three months after receiving MVA85A vaccination (males and females) Additional criteria to be met for subjects in group C: Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation) Additional criteria to be met for subjects in group D: Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation) Willingness to use continuous effective barrier contraception for three months after receiving MVA85A vaccination (males and females) Exclusion Criteria: Clinical, radiological, or laboratory evidence of current active TB disease Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT test (>17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide poola Previous vaccination with candidate TB vaccine MVA85A or candidate TB vaccine FP85A Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse History of serious psychiatric condition Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study vaccine Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the studyb Positive HBsAg, HCV or HIV antibodies Female currently lactating, confirmed pregnancy or intention to become pregnant during study period Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 60 days prior to dosing with the study vaccine, or planned use during the study period Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk or may influence the result of the study or may affect the volunteer's ability to participate in the study Additional exclusion criteria for subjects in group A: Previous vaccination with BCG Additional exclusion criteria for subjects in group B: Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A Previous vaccination with BCG Additional exclusion criteria for subjects in group C: None Additional exclusion criteria for subjects in group D: Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>BCG-naive subjects receiving intradermal challenge injection of BCG and challenge site punch biopsy | Biological: BCG: 100 microlitres   2-8 x 105 pfu<br>* BCG vaccination at day C (challenge day) then punch biopsy at day C+14<br>|
| Experimental: Group B<br>BCG-naïve subjects receiving intradermal injection of MVA85A followed by intradermal challenge injection of BCG and challenge site punch biopsy | Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres   2-8 x 105 pfu<br>* MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14<br>|
| Experimental: Group C<br>BCG-experienced subjects receiving intradermal challenge injection of BCG and challenge site punch biopsy | Biological: BCG: 100 microlitres   2-8 x 105 pfu<br>* BCG vaccination at day C (challenge day) then punch biopsy at day C+14<br>|
| Experimental: Group D<br>BCG-experienced subjects receiving intradermal injection of MVA85A followed by intradermal challenge injection of BCG and challenge site punch biopsy | Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres   2-8 x 105 pfu<br>* MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Culture and RT-PCR quantification of BCG in challenge site biopsy |  | 10 weeks post biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue |  | 10 weeks post biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mycobacterium tuberculosis, BCG, MVA85A