A BCG Challenge Model Study to Assess Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A

August 29, 2012 updated by: University of Oxford

A Phase 1 Study to Evaluate a BCG Challenge Model as a Method of Assessing Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A, Alone and in Combination

The purpose of this study is to evaluate the BCG 'challenge' model a four-arm study design has been chosen. Twelve subjects will be recruited into each arm of the study. Allocation of BCG-naïve volunteers to either group A or B, and BCG-vaccinated volunteers to either group C or D, will be performed on a one-to-one alternating basis. Subjects in each group will be challenged by BCG administered intradermally. Prior to challenge, pre-existing immunity to TB will be induced by vaccination with BCG, MVA85A, and both in combination (when compared to BCG- & MVA85A-naïve individuals). BCG quantification will be assessed by analysing the tissue obtained in a punch biopsy of volunteers' skin over the site of BCG 'challenge' vaccination. Any reduction in BCG quantification between groups will then be correlated to existing (and future) laboratory assays of vaccine-induced immune responses in order to identify potential immunological correlates of protection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxon
      • Oxford, Oxon, United Kingdom, OX3 7LJ
        • Centre for Clinical Vaccinology and Tropical Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy adult aged 18-55 years
  • Resident in or near Oxford for the duration of the study period
  • No relevant findings in medical history or on physical examination
  • Willingness to allow the Investigators to discuss the individual's medical history with their GP
  • Willingness to use effective contraception for the duration of the study period (females only)
  • Agreement to refrain from blood donation during the course of the study
  • Willingness to give written informed consent
  • Agreement to allow the Investigator to register volunteer 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 study requirements

Additional criteria to be met for subjects in group A:

  • None

Additional criteria to be met for subjects in group B:

  • Willingness to use continuous effective barrier contraception for three months after receiving
  • MVA85A vaccination (males and females)

Additional criteria to be met for subjects in group C:

  • Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)

Additional criteria to be met for subjects in group D:

  • Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)
  • Willingness to use continuous effective barrier contraception for three months after receiving MVA85A vaccination (males and females)

Exclusion Criteria:

  • Clinical, radiological, or laboratory evidence of current active TB disease
  • Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT test (>17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide poola
  • Previous vaccination with candidate TB vaccine MVA85A or candidate TB vaccine FP85A
  • Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory 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 study vaccine
  • Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the studyb
  • Positive HBsAg, HCV or HIV antibodies
  • Female currently lactating, confirmed pregnancy or intention to become pregnant during study period
  • Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 60 days prior to dosing with the study vaccine, or planned use during the study 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 volunteer at risk or may influence the result of the study or may affect the volunteer's ability to participate in the study

Additional exclusion criteria for subjects in group A:

  • Previous vaccination with BCG

Additional exclusion criteria for subjects in group B:

  • Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A
  • Previous vaccination with BCG

Additional exclusion criteria for subjects in group C:

  • None

Additional exclusion criteria for subjects in group D:

  • Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
BCG-naive subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
BCG vaccination at day C (challenge day) then punch biopsy at day C+14
Experimental: Group B
BCG-naïve subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14
Experimental: Group C
BCG-experienced subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
BCG vaccination at day C (challenge day) then punch biopsy at day C+14
Experimental: Group D
BCG-experienced subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Culture and RT-PCR quantification of BCG in challenge site biopsy
Time Frame: 10 weeks post biopsy
10 weeks post biopsy

Secondary Outcome Measures

Outcome Measure
Time Frame
Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue
Time Frame: 10 weeks post biopsy
10 weeks post biopsy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

August 31, 2010

First Submitted That Met QC Criteria

September 1, 2010

First Posted (Estimate)

September 2, 2010

Study Record Updates

Last Update Posted (Estimate)

August 30, 2012

Last Update Submitted That Met QC Criteria

August 29, 2012

Last Verified

October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TB023

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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