A Clinical Challenge Study of BCG in Healthy Volunteers

January 21, 2015 updated by: University of Oxford

A Clinical Challenge Study to Quantify BCG at the Challenge Site of Healthy Volunteers Receiving Either Intradermal BCG SSI or BCG TICE at Standard or High Dose

TB031 is a challenge study comparing two different strains of the Bacille Calmette-Guérin (BCG) vaccine at standard and high dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Currently, to assess vaccine efficacy against tuberculosis (TB) there is no alternative to large randomized controlled trials. These efficacy trials for novel TB vaccines are difficult, long and very costly. For this reason there is an urgent need for a valid, reliable, and strong correlate of protection which can help distinguish between candidate TB vaccines undergoing phase I trials, and thereby allow the vaccine development field to advance more quickly, and in a more cost-effective manner.

This study aims to address the current lack of immunological correlates in the TB vaccine field. As an alternative to phase II field trials, human challenge models can provide an evaluation of preliminary efficacy of vaccine candidates. Challenge models, with their concept of deliberate infectious challenge of human volunteers, have been well established for pathogens such as malaria, typhoid and dengue, and these models have greatly facilitated vaccine development. At present there is no safe human challenge model of Mycobacterium tuberculosis (M. tb) infection to enable proof-of-concept efficacy evaluation of candidate vaccines.

Whilst scientists cannot use M. tb as a challenge agent to evaluate efficacy in a clinical trial for safety and ethical reasons, they can use another mycobacterium, attenuated Mycobacterium bovis, as a surrogate for M. tb infection. Attenuated Mycobacterium bovis is the mycobacterial strain in BCG and is safe to use in humans. An effective vaccine against M. tb should also be effective against BCG. After injection into humans, BCG replicates, and an effective TB vaccine should reduce this BCG replication. The BCG challenge model is based on this premise. In the human BCG challenge model, BCG is administered intradermally and the degree of BCG growth suppression is quantified by analysing the tissue obtained in a punch biopsy of volunteers' skin over the BCG 'challenge' site.

This study aims to use two different strains of BCG, each at standard and high dose, to optimise this BCG challenge model.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Not Applicable

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
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2TB
        • The Wellcome Trust Clinical Research Facility, University of Birmingham

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:

Volunteers must meet all of the following criteria to enter the study:

  • Healthy adult aged 18-55 years
  • BCG naïve
  • Resident in or near Oxford (for CCTVM) or Birmingham (for WTCRF) for the duration of the study period
  • No relevant findings in medical history or on physical examination
  • Allow the Investigators to discuss the volunteer's medical history with their GP
  • Use effective contraception for the duration of the study period (females only)
  • Agreement to refrain from blood donation during the duration of the study
  • Give written informed consent
  • 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

Exclusion Criteria:

Volunteers must meet none of the following criteria to enter the study:

  • 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 BCG, or any candidate TB vaccine
  • Within the last year had close household contact with an individual with smear positive pulmonary tuberculosis
  • 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 challenge agent
  • 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 study
  • Positive HBsAg, HCV or HIV antibodies
  • Female confirmed pregnant or intention to become pregnant during study period, or currently lactating
  • Current involvement in another trial that involves regular blood tests or an investigational medicinal product
  • Use of an investigational medicinal product or non-registered drug, live vaccine, or investigational medical device for four weeks prior to dosing with the study challenge agent
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned challenge 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

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

  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
10 BCG-naïve subjects receiving intradermal BCG SSI at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later.
Drug: BCG SSI
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)
Experimental: Group B
10 BCG-naïve subjects receiving BCG Tice at standard dose (2-8 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later.
Drug: BCG Tice
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Tice
Experimental: Group C
10 BCG-naïve subjects receiving intradermal BCG SSI at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later.
Drug: BCG SSI
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)
Experimental: Group D
10 BCG-naïve subjects receiving intradermal BCG Tice at high dose (6-24 x 10^5 cfu) followed by a punch biopsy at the challenge site 14 days later.
Drug: BCG Tice
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Tice
Experimental: Group E
8-12 BCG-naïve subjects receiving the optimal strain and dose of intradermal BCG identified from preliminary results obtained from Group A, B, C and D, followed by a punch biopsy at the challenge site 14 days later.
Drug: BCG SSI
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)
Drug: BCG Tice
Intradermal injection
Other Names:
  • Bacille Calmette-Guérin Tice

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantity of BCG at challenge site
Time Frame: At Day 14
To evaluate and compare the amount of BCG (measured by CFU count and PCR) from a biopsy taken from the intradermal BCG challenge site in healthy BCG-naïve adults receiving either BCG SSI or BCG Tice at either standard or high dose
At Day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune response markers
Time Frame: Up to Day 14
To identify laboratory markers of the immune response that correlate with the levels of mycobacterial suppression at the BCG challenge site
Up to Day 14

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local and systemic adverse events
Time Frame: Up to Day 28
To evaluate and compare local and systemic adverse events between the different challenge models through actively and passively collected data on adverse events.
Up to Day 28
Mycobacterial Growth Inhibition Assays
Time Frame: Up to day 14
Use of Mycobacterial Growth Inhibition Assays to evaluate the effect of recent BCG vaccination on in-vitro ability to control Staphylococcus aureus, and potentially also Klebsiella, Group B streptococcus and Escherichia coli.
Up to day 14

Collaborators and Investigators

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

Sponsor

University of Oxford

Collaborators

University of Birmingham
Aeras

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

Helpful Links

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

March 1, 2014

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

March 10, 2014

First Submitted That Met QC Criteria

March 14, 2014

First Posted (Estimate)

March 17, 2014

Study Record Updates

Last Update Posted (Estimate)

January 22, 2015

Last Update Submitted That Met QC Criteria

January 21, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TB031

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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