Safety Study of Tuberculosis Vaccines AERAS-402 and MVA85A

Study Overview
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Brief Summary
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This trial will investigate the administration of two new tuberculosis vaccines, called AERAS-402 and MVA85A. The purpose of this trial is to assess what happens when both of these vaccines are given one after the other. The trial will assess the safety of both vaccines and also their ability to stimulate an immune response within the body. It is hoped that when these two vaccines are given in sequence, the combined immune response is even better than when each vaccine is used individually.

Official Title
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A Phase I, Open Label Trial to Evaluate the Safety and Immunogenicity of AERAS-402 Followed by MVA85A in BCG Vaccinated Adults (TB032)

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: AERAS-402
* Biological: MVA85A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to enter the trial: Healthy adult aged 18-55 years Resident in or near Oxford (for CCVTM) or Birmingham (for WTCRF; and able to travel to Oxford for vaccinations) for the duration of the trial period No relevant findings in medical history or on physical examination Confirmation of prior vaccination with BCG not less than 6 months prior to projected trial vaccination date (by visible BCG scar on examination or written documentation) Allow the Investigators to discuss the individual's medical history with their GP Use effective contraception for the duration of the trial period (females only) Refrain from blood donation during the trial Give written informed consent Allow the Investigator to register subject details with a confidential database to prevent concurrent entry into clinical trials Agrees to avoid elective surgery for the duration of the trial Has a body mass index (BMI) between 18 and 33 (weight/height2) by nomogram Able and willing (in the Investigator's opinion) to comply with all the trial requirements Exclusion Criteria: Subjects must meet none of the following criteria to enter the trial: Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens Clinical, radiological, or laboratory evidence of current active TB disease Shared a residence within one year prior to day 0 with an individual on anti-tuberculosis treatment or with culture- or smear-positive pulmonary tuberculosis Previous treatment for active or latent tuberculosis infection Received a TST within 90 days prior to day 0 Received a systemic antibiotic within 14 days prior to day 0 Inability to discontinue daily medications other than the following during the trial: oral contraceptives, vitamins, nonprescription nutritional supplements, aspirin, antihistamines, antihypertensives, antidepressants, inhaled steroids, bronchodilators, and any other stable, regular medication not deemed to have an impact on safety or immunogenicity. Previous vaccination with candidate vaccine MVA85A or candidate vaccine FP85A or any other recombinant MVA or adenoviral vaccine; AERAS-402; or any other investigational M. tb vaccine Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), autoimmune disease, cancer (except BCC or CIS), cardiovascular 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 trial vaccine, including eggs Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the subject in the triala Positive HBsAg, HCV or HIV antibodies Female currently lactating, confirmed pregnancy or intention to become pregnant during trial period Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the trial vaccine for 30 days prior to dosing with the trial vaccine, or planned use during the trial 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 subject at risk or may influence the result of the trial or may affect the subject's ability to participate in the trial

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Two doses of AERAS-402 (1x10^11 vp intramuscular injection) followed by one dose of MVA85A (1x10^8 pfu intradermal injection) | Biological: AERAS-402<br>* Intramuscular needle injection 1x10^11 vp<br>* Other names: Ad35 TB-S;Biological: MVA85A<br>* Intradermal needle injection 1x10^8 pfu<br>* Other names: AERAS-485;|
| Experimental: Group B<br>One dose of AERAS-402 (1x10^11 vp intramuscular injection) followed by one dose of MVA85A (1x10^8 pfu intradermal injection) | Biological: AERAS-402<br>* Intramuscular needle injection 1x10^11 vp<br>* Other names: Ad35 TB-S;Biological: MVA85A<br>* Intradermal needle injection 1x10^8 pfu<br>* Other names: AERAS-485;|
| Experimental: Group C<br>Three doses of AERAS-402 (1x10^11 vp intramuscular injection) | Biological: AERAS-402<br>* Intramuscular needle injection 1x10^11 vp<br>* Other names: Ad35 TB-S;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of AERAS-402 followed by MVA85A | To evaluate the safety profile of multiple doses of AERAS-402 alone, compared to one and two doses of AERAS-402 followed by MVA85A in healthy, BCG vaccinated adults, measured by number and severity of local and systemic adverse events | 3 months after final vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of AERAS-402 followed by MVA85A | To evaluate and compare the immune responses as described by flow cytometric intracellular cytokine staining, antibody serology, and Elispot assays of multiple doses of AERAS-402 alone, compared to one and two doses of AERAS-402 followed by MVA85A in healthy, BCG vaccinated adults | 12-18 months after first vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Phase I, MVA85A, AERAS-402