Safety Study of ChAdOx1 85A Vaccination With and Without MVA85A Boost in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase I trial to evaluate the safety and immunogenicity of a ChAdOx1 85A vaccination with and without MVA85A boost in healthy BCG vaccinated adults.

Official Title
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Phase I Trial to Evaluate the Safety and Immunogenicity of a ChAdOx1 85A Vaccination With and Without MVA85A Boost in Healthy BCG Vaccinated Adults

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: ChAdOx1 85A
* 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 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 vaccination with any recombinant MVA, FP or adenoviral vector Clinically significant history of skin disorder, allergy, 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 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 trial 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 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Starter Group<br>The first six volunteers will receive one dose of 5x10^9vp of ChAdOx1 85A intramuscular injection. | Biological: ChAdOx1 85A<br>* Intramuscular injection<br>|
| Experimental: Group A<br>12 subjects will receive one dose of 2.5x10^10vp of ChAdOx1 85A intramuscular injection. | Biological: ChAdOx1 85A<br>* Intramuscular injection<br>|
| Experimental: Group B<br>12 subjects will receive one dose of 2.5x10^10vp of ChAdOx1 85A by intramuscular injection, followed by a boost dose of 1x10^8pfu of MVA85A by intramuscular injection 56 days later. | Biological: ChAdOx1 85A<br>* Intramuscular injection<br>Biological: MVA85A<br>* Intramuscular injection<br>|
| Experimental: Group C<br>12 subjects will receive two doses of 2.5x10^10vp of ChAdOx1 85A by intramuscular injection at day 0 and day 28, followed by a boost dose of 1x10^8pfu of MVA85A by intramuscular injection at day 119. | Biological: ChAdOx1 85A<br>* Intramuscular injection<br>Biological: MVA85A<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of ChAdOx1 85A vaccination with, and without, MVA85A boost vaccination in healthy, BCG vaccinated adults. | To evaluate the safety in healthy BCG-vaccinated subjects of ChAdOx1 85A vaccination, with and without MVA85A boost vaccination, by actively and passively collecting data on adverse events. | Six months following vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the T-cell immune response of ChAdOx1 85A vaccination compared with ChAdOx1 85A vaccination with MVA85A boost vaccination. | To evaluate the systemic and mucosal cellular immunogenicity in healthy BCG-vaccinated subjects of ChAdOx1 85A vaccination, compared with ChAdOx1 85A vaccination with MVA85A boost vaccination, by comparing laboratory markers of cell mediated immunity in blood. | Six months following vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Immunogenicity