Study Evaluating Aerosol and Intradermal Administration of a Candidate Tuberculosis (TB) Vaccine, MVA85A, as a Way to Increase Immune Response and Avoid Anti-vector Immunity

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT01954563

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Boost vaccinations sometimes have no effect because the body has got used to the vaccine and no longer reacts to it. We are therefore investigating whether vaccinating with aerosolised MVA85A (a candidate tuberculosis vaccine) followed by a boost MVA85A intradermal vaccination (or vice versa) avoids this and increases the immune response to vaccination.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: MVA85A	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase I Trial Evaluating Mucosal Administration of a Candidate TB Vaccine, MVA85A, as a Way to Induce Potent Local Cellular Immune Responses and Avoid Anti-vector Immunity

Study Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Receive 5x10^7 MVA85A by aerosol at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.
Experimental: Group 2 Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost aerosol vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.
Experimental: Group 3 Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.	Biological: MVA85A Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.

Arm

Intervention/Treatment

Experimental: Group 1

Receive 5x10^7 MVA85A by aerosol at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.

Biological: MVA85A

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.

Experimental: Group 2

Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost aerosol vaccination of 5x10^7 MVA85A at day 28.

Biological: MVA85A

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.

Experimental: Group 3

Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.

Biological: MVA85A

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.

Outcome Measures

Primary Outcome Measures

Safety of 5 x 10^7 pfu dose of MVA85A administered by aerosol and compared to the same dose administered intradermally [24 weeks from enrolment]
Actively and passively collected data on adverse events

Secondary Outcome Measures

Immunogenicity of 5 x 10^7 pfu dose of MVA85A administered by aerosol followed by the same dose administered intradermally, compared to the same dose of MVA85A given intradermally and boosted by aerosol [24 weeks from enrolment]
Characterise mucosal and systemic immunogenicity of viral vector (MVA) and insert (Ag85A) by comprehensive characterisation of humoral and cellular immune responses Evaluate functional relevance of anti-vector immunity induced by aerosol and systemic immunisation in MVA85A-prime followed by homologous MVA85A-boost administered 4 weeks later

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 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:

Any respiratory disease, including asthma
Current smoker
Clinically significant abnormality on screening chest x-ray
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
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
Previous vaccination with candidate vaccine MVA85A or candidate vaccine FP85A or any other recombinant MVA vaccine
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, sedative drugs, or any local or general anaesthetic agents
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford	Oxford	Oxfordshire	United Kingdom	OX3 7LE

Sponsors and Collaborators

University of Oxford

Investigators

Principal Investigator: Helen McShane, University of Oxford

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Jenner Institute Clinical Trials

Publications

None provided.

Responsible Party:

University of Oxford

ClinicalTrials.gov Identifier:

NCT01954563

Other Study ID Numbers:

TB035

First Posted:

Oct 1, 2013

Last Update Posted:

Jan 28, 2016

Last Verified:

Jan 1, 2016

Keywords provided by University of Oxford

Tuberculosis

Vaccine

Immunogenicity

Additional relevant MeSH terms:

Tuberculosis

Study Results

No Results Posted as of Jan 28, 2016