MVA85A Aerosol vs Intramuscular Vaccination in Adults With Latent Mycobacterium Tuberculosis (M. tb) Infection

Study Overview
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Brief Summary
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TB040 is a clinical trial to investigate and compare the effects of a candidate Tuberculosis (TB) vaccine, MVA85A, administered by the aerosol inhaled route and the intramuscular route in healthy adult volunteers who are latently infected with Mycobacterium tuberculosis.

Official Title
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A Phase I Trial to Compare the Safety and Immunogenicity of Candidate TB Vaccine MVA85A Administered by the Aerosol Inhaled Route and the Intramuscular Route in Healthy Adult Volunteers Who Are Latently Infected With Mycobacterium Tuberculosis

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: Aerosol inhaled MVA85A
* Biological: Intramuscular MVA85A
* Biological: Intramuscular Saline placebo
* Biological: Aerosol inhaled Saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers must meet all of the following criteria to enter the trial: Healthy adult aged 18-55 years Resident in or near Oxford, Birmingham or London for the duration of the trial period Screening IGRA positive Ineligible for chemoprophylaxis for latent M.tb infection, declined prophylaxis or considered low risk due to distant contact history Chest Computed Tomography (CT) normal; or abnormal with features consistent with primary M.tb infection but no features suggestive of active disease No relevant findings in medical history or on physical examination Allow the Investigators to discuss the individual's medical history with their General Practitioner 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 volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical trials Able and willing (in the Investigator's opinion) to comply with all the trial requirements Exclusion Criteria: Volunteers must meet none of the following criteria to enter the trial: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the trial period Prior vaccination with candidate vaccine MVA85A, candidate vaccine FP85A,any other recombinant MVA vaccine or any other candidate TB vaccine Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse 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, sedative drugs, or any local or general anaesthetic agents Pregnancy, lactation or intention to become pregnant during trial period Any respiratory disease, including asthma Current smoker Clinically significant abnormality on screening CT thorax Clinically significant abnormality of pulmonary function tests Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs Clinical, radiological, or laboratory evidence of current active TB disease Past treatment for TB disease Any clinically significant abnormality of screening blood or urine tests Positive HBsAg, HCV or HIV antibodies Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the trial or impair interpretation of the trial data

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Starter Group<br>Receive 1x10^7 pfu aerosol inhaled MVA85A at day 0. | Biological: Aerosol inhaled MVA85A<br> <br> * Other names: MVA85A;|
| Experimental: Group A<br>Receive 5x10^7 pfu aerosol inhaled MVA85A, and intramuscular saline placebo both at day 0. | Biological: Aerosol inhaled MVA85A<br> <br> * Other names: MVA85A;Biological: Intramuscular Saline placebo<br> <br> * Other names: Saline;|
| Experimental: Group B<br>Receive 5x10^7 pfu intramuscular MVA85A, and aerosol inhaled saline placebo both at day 0. | Biological: Intramuscular MVA85A<br> <br> * Other names: MVA85A;Biological: Aerosol inhaled Saline placebo<br> <br> * Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) | Actively and passively collected data on adverse events via diary card for 14 days after vaccination and at each visit over 6 months. | Up to Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory Markers of Immunity | Evaluation of ex-vivo ELISpot and intracellular cytokine staining in blood and bronchoalveolar lavage (BAL) samples. | Up to Day 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MVA85A, Tuberculosis, Vaccine, Aerosol