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A Trial of the C-Tb Skin Test, When Given Intradermally to Healthy Volunteers Previously Vaccinated With BCG (TESEC-03)

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

C-Tb

2 TU Tuberculin PPD RT 23 SSI

About this trial

This is an interventional diagnostic trial for Tuberculosis focused on measuring tuberculosis, rdESAT-6, CFP-10, skin test, diagnostic test

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Has signed an informed consent
Aged 18 to 65 years
Is known to be BCG vaccinated (documented in medical files and/or by the presence of a BCG scar)
Is healthy according to a medical examination and medical history at screening
Is willing and likely to comply with the trial procedures
Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

Has a history of tuberculosis or has been in close contact to a person with active tuberculosis within 5 years from trial inclusion
Has a positive QuantiFERON®-TB Gold In-Tube assay at inclusion
Laboratory parameters outside of normal range judged by site investigator to be clinically significant
Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products)
Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
Has been vaccinated with BCG < 6 months prior to the day of inclusion
Has been tuberculin (TST) tested < 6 months prior to the day of inclusion
Has a known congenital or acquired immune deficiency
Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
Is infected with HIV
Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
Has a condition where blood drawings pose more than minimal risk for the volunteer, such as haemophilia, other coagulation disorders, or significantly impaired venous access
Currently participating in another clinical trial with an investigational or non investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing
Has participated in previous clinical trials investigating the ESAT-6 and/or CPP-10 antigens
Is pregnant, breast-feeding or intending to get pregnant
Is a female not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures
Has a history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1
Has a positive urine drug screen at Visit 1 and Visit 2 (i.e., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates)
Has a positive alcohol breath test at Visit 1 and Visit 2. [NOTE: subjects must be told to avoid consumption of alcoholic beverages for at least 24 hours prior to attending the Centre]
Has a condition which in the opinion of the investigator is not suitable for participation in the study

Sites / Locations

Surrey Clinical Research Centre, University of Surrey

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

0.1µg/0.1 mL C-Tb

2TU Tuberculin PPD RT 23 SSI

Arm Description

The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme

Outcomes

Primary Outcome Measures

The diameter of induration at the injection sites measured transversely to the long axis of the forearm 2-3 days after application of the agents

Secondary Outcome Measures

Injection site adverse reactions within 28 days after application of the agents

All adverse events occurring within 28 days after application of the agents

Laboratory safety parameters of haematology and biochemistry

In vitro IFN-γ response as measured by the QuantiFERON®-TB Gold In-Tube assay from blood samples taken at screening and 28 days after the injections of the skin test agents

Full Information

NCT ID

NCT01242475

First Posted

November 16, 2010

Last Updated

January 18, 2013

Sponsor

Statens Serum Institut

1. Study Identification

Unique Protocol Identification Number

NCT01242475

Brief Title

A Trial of the C-Tb Skin Test, When Given Intradermally to Healthy Volunteers Previously Vaccinated With BCG

Acronym

TESEC-03

Official Title

A Phase IIa Specificity Trial of the Diagnostic Agent C-Tb, When Given Intradermally by the Mantoux Technique to Healthy Volunteers Previously Vaccinated With BCG

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

April 2011 (undefined)

Primary Completion Date

November 2011 (Actual)

Study Completion Date

November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Statens Serum Institut

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

A new, more specific skin test to detect tuberculosis has been developed by Statens Serum Institut in Denmark. The new skin test is named C-Tb and like the current Tuberculin a positive test result will show as redness and/or swelling at the injection site, while a negative test will leave no reactions. The aim of this study is to test the C-Tb skin test in healthy adults previously BCG vaccinated to determine if healthy non tuberculosis infected individuals has a truly negative test result (this is called determining the specificity of the skin test). To be able to compare the new skin test with the current Tuberculin skin test volunteers will be injected with both the C-Tb and the TST skin test.

Detailed Description

The trial is designed to investigate the specificity of C-Tb under various definitions of cut-off in a double blind randomised, split-body study comparing 0.1 µg/0.1 mL C-Tb with the reference agent 2 T.U. Tuberculin PPD RT23 SSI. (Each volunteer receives the C-Tb agent in one arm and the 2 T.U. Tuberculin PPD in the other arm). The C-Tb and 2 T.U. Tuberculin PPD agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearm according to a double blind randomisation scheme. The primary objective of the trial is to assess the specificity of the C-Tb test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a negative outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to healthy BCG vaccinated adults The specificity of the C-Tb test is defined as the relative frequency of subjects in a healthy population (i.e., no exposure to MTb) who have an induration response < cut-off after a C-Tb test. Similarly the sensitivity is defined as the relative frequency of patients with an induration response ≥ cut-off in TB patients. An optimal cut-off point of being infected will be determined by combing the results from the present specificity study with those from a parallel sensitivity study in patients recently diagnosed with TB. The secondary objectives of the trial are to compare the induration response of C-Tb with the induration response of 2 T.U. Tuberculin PPD RT 23 SSI, to compare the induration response of C-Tb with the in-vitro IFN-γ response measured at screening and 28 days after the injections of the skin test agents using the QuantiFERON®-TB Gold In-Tube assay and finally to record all adverse events occurring within 28 days after application of the agents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

tuberculosis, rdESAT-6, CFP-10, skin test, diagnostic test

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

151 (Actual)

8. Arms, Groups, and Interventions

Arm Title

0.1µg/0.1 mL C-Tb

Arm Type

Experimental

Arm Description

The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme

Arm Title

2TU Tuberculin PPD RT 23 SSI

Arm Type

Active Comparator

Arm Description

The C-Tb and 2 TU Tuberculin PPD RT 23 SSI agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a double blind randomisation scheme

Intervention Type

Biological

Intervention Name(s)

C-Tb

Other Intervention Name(s)

rdESAT-6 + rCFP-10

Intervention Description

The C-Tb agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme

Intervention Type

Biological

Intervention Name(s)

2 TU Tuberculin PPD RT 23 SSI

Other Intervention Name(s)

PPD, Tuberculin

Intervention Description

The 2TU Tuberculin PPD RT 23 SSI agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearms according to a double blind randomisation scheme

Primary Outcome Measure Information:

Title

The diameter of induration at the injection sites measured transversely to the long axis of the forearm 2-3 days after application of the agents

Time Frame

From injections to 2-3 days after application of the agents

Secondary Outcome Measure Information:

Title

Injection site adverse reactions within 28 days after application of the agents

Time Frame

Onset between the injections and 28 days after the injections

Title

All adverse events occurring within 28 days after application of the agents

Time Frame

Onset between the injections and 28 days after the injections

Title

Laboratory safety parameters of haematology and biochemistry

Time Frame

Onset between the injections and 28 days after the injections

Title

In vitro IFN-γ response as measured by the QuantiFERON®-TB Gold In-Tube assay from blood samples taken at screening and 28 days after the injections of the skin test agents

Time Frame

Onset between the injections and 28 days after the injections

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Has signed an informed consent Aged 18 to 65 years Is known to be BCG vaccinated (documented in medical files and/or by the presence of a BCG scar) Is healthy according to a medical examination and medical history at screening Is willing and likely to comply with the trial procedures Is prepared to grant authorized persons access to their medical records Exclusion Criteria: Has a history of tuberculosis or has been in close contact to a person with active tuberculosis within 5 years from trial inclusion Has a positive QuantiFERON®-TB Gold In-Tube assay at inclusion Laboratory parameters outside of normal range judged by site investigator to be clinically significant Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products) Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) Has been vaccinated with BCG < 6 months prior to the day of inclusion Has been tuberculin (TST) tested < 6 months prior to the day of inclusion Has a known congenital or acquired immune deficiency Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis) Is infected with HIV Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites Has a condition where blood drawings pose more than minimal risk for the volunteer, such as haemophilia, other coagulation disorders, or significantly impaired venous access Currently participating in another clinical trial with an investigational or non investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing Has participated in previous clinical trials investigating the ESAT-6 and/or CPP-10 antigens Is pregnant, breast-feeding or intending to get pregnant Is a female not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures Has a history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1 Has a positive urine drug screen at Visit 1 and Visit 2 (i.e., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates) Has a positive alcohol breath test at Visit 1 and Visit 2. [NOTE: subjects must be told to avoid consumption of alcoholic beverages for at least 24 hours prior to attending the Centre] Has a condition which in the opinion of the investigator is not suitable for participation in the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Birgit Thierry-Carstensen

Organizational Affiliation

Statens Serum Institut

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

David JM Lewis, MD

Organizational Affiliation

Surrey Clinical Research Centre, University of Surrey

Official's Role

Principal Investigator

Facility Information:

Facility Name

Surrey Clinical Research Centre, University of Surrey

City

Surrey

State/Province

Guildford, Surrey

ZIP/Postal Code

GU2 7XP

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Trial of the C-Tb Skin Test, When Given Intradermally to Healthy Volunteers Previously Vaccinated With BCG

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