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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

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
MVA85A
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, Vaccine, Immunogenicity

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Safety of 5 x 10^7 pfu dose of MVA85A administered by aerosol and compared to the same dose administered intradermally
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
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

Full Information

First Posted
September 26, 2013
Last Updated
January 27, 2016
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT01954563
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Tuberculosis, Vaccine, Immunogenicity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Receive 5x10^7 MVA85A by aerosol at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost aerosol vaccination of 5x10^7 MVA85A at day 28.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Receive 5x10^7 MVA85A by intradermal injection at day 0, followed by boost intradermal vaccination of 5x10^7 MVA85A at day 28.
Intervention Type
Biological
Intervention Name(s)
MVA85A
Intervention Description
Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia with an antigen 85A insert.
Primary Outcome Measure Information:
Title
Safety of 5 x 10^7 pfu dose of MVA85A administered by aerosol and compared to the same dose administered intradermally
Description
Actively and passively collected data on adverse events
Time Frame
24 weeks from enrolment
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
24 weeks from enrolment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen McShane
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31039172
Citation
Manjaly Thomas ZR, Satti I, Marshall JL, Harris SA, Lopez Ramon R, Hamidi A, Minhinnick A, Riste M, Stockdale L, Lawrie AM, Vermaak S, Wilkie M, Bettinson H, McShane H. Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A: A phase I randomised controlled trial. PLoS Med. 2019 Apr 30;16(4):e1002790. doi: 10.1371/journal.pmed.1002790. eCollection 2019 Apr.
Results Reference
derived
Links:
URL
http://www.jenner.ac.uk/clinicaltrials
Description
Jenner Institute Clinical Trials

Learn more about this trial

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

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