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A Trial of the C-Tb Skin Test, When Given Intradermally to Adult Patients Recently Diagnosed With Active Tuberculosis (TB) (TESEC-04)

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
C-Tb
2 TU Tuberculin PPD RT 23 SSI
Sponsored by
Statens Serum Institut
About
Eligibility
Locations
Arms
Outcomes
Full info

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 SexesDoes not accept healthy volunteers

Inclusion Criteria (HIV negative patients):

  1. Has signed an informed consent
  2. Aged 18 to 65 years

  3. Has been diagnosed with active TB:

    1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and at least 1 documented positive sputum smear microscopy result or
    2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and a positive culture result
  4. Is HIV negative confirmed by 2 two rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA))
  5. Is willing and likely to comply with the trial procedures
  6. Is prepared to grant authorized persons access to their medical record

Inclusion Criteria (HIV positive patients):

  1. Has signed an informed consent
  2. Aged 18 to 65 years
  3. Has a compatible clinical picture of TB according to South African guidelines with the intention to treat

  4. Is HIV positive confirmed by:

    1. 2 positive rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA)) or
    2. 1 positive rapid tests (Abbott-DetermineTM HIV-1/2 or Sensa (Seyama Solutions, SA)) and an additional confirmatory ELISA (Enzygnost anti-HIV-1/2 Plus)
  5. Is willing and likely to comply with the trial procedures
  6. Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

  1. Has been in treatment for TB for more than 2 weeks
  2. Has a known MDR/XDR-TB
  3. Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response except for HIV treatment (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products)
  4. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
  5. Has been vaccinated with BCG < 6 months prior to the day of inclusion
  6. Has been tuberculin (TST) tested < 6 months prior to the day of inclusion
  7. Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
  8. 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
  9. Has a condition where blood drawings pose more than minimal risk for the patient, such as haemophilia, other coagulation disorders, or significantly impaired venous access
  10. 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
  11. Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
  12. Is pregnant, breastfeeding or intending to get pregnant
  13. Has a condition which in the opinion of the investigator is not suitable for participation in the study

Sites / Locations

  • University of Cape Town Lung Institute (Pty) Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

0.1 µg/0.1 mL C-Tb

2 TU 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

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

Full Information

First Posted
November 15, 2010
Last Updated
April 16, 2015
Sponsor
Statens Serum Institut
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1. Study Identification

Unique Protocol Identification Number
NCT01241188
Brief Title
A Trial of the C-Tb Skin Test, When Given Intradermally to Adult Patients Recently Diagnosed With Active Tuberculosis (TB)
Acronym
TESEC-04
Official Title
A Phase IIb Sensitivity Trial of the Diagnostic Agent C-Tb, When Given Intradermally by the Mantoux Technique to Adult Patients Recently Diagnosed With Active TB
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Statens Serum Institut

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Tuberculosis (TB) continues to be the most important bacterial infection worldwide and therefore new improved diagnostic tests are needed to help doctors in diagnosing TB. The new skin test is named C-Tb. Like the current Tuberculin Skin Test (TST), the C-Tb test is injected just under the skin and will when positive show a redness and/or swelling at the injection site while a negative test will leave no reactions. The aim of this trial is to test the C-Tb skin test in adults diagnosed with TB to determine if a TB infected individual has a truly positive test result (this is called to find the sensitivity of the skin test).
Detailed Description
The trial is designed to investigate the sensitivity of C-Tb using various sizes of cut-off of induration 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 2 T.U. Tuberculin PPD RT 23 SSI in the other arm). Two groups of adult patients recently diagnosed with active TB will be investigated; patients in the main group will NOT have a co-infection with HIV and patients in the second group will have a co-infection with HIV. 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. The primary objectives are to assess the sensitivity 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 positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV negative adult patients recently diagnosed with active TB and to assess the sensitivity 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 positive outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to HIV positive adult patients recently diagnosed with active TB The sensitivity is defined as the relative frequency of patients with an induration response ≥ cut-off in TB patients. Similarly the specificity of the C-Tb test is defined as the relative frequency of subjects in a healthy population (i.e., no exposure to M. tuberculosis) who have an induration response < cut-off after a C-Tb test. An optimal cut-off point of being infected will be determined by combing the results from the present sensitivity study with those from a parallel specificity study in (BCG vaccinated) individuals with no previous exposure to M. tuberculosis. The secondary objectives of the trial is 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 using the QuantiFERON®-TB Gold In Tube assay, to correlate the induration response to the initial CD4+ counts in HIV positive patients and to record all adverse events (local and systemic) 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
253 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.1 µg/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
2 TU 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 2 TU 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 aplication
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
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
No
Eligibility Criteria
Inclusion Criteria (HIV negative patients): Has signed an informed consent Aged 18 to 65 years Has been diagnosed with active TB: has a compatible clinical picture of TB according to South African guidelines with the intention to treat and at least 1 documented positive sputum smear microscopy result or has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and a positive culture result Is HIV negative confirmed by 2 two rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA)) Is willing and likely to comply with the trial procedures Is prepared to grant authorized persons access to their medical record Inclusion Criteria (HIV positive patients): Has signed an informed consent Aged 18 to 65 years Has a compatible clinical picture of TB according to South African guidelines with the intention to treat Is HIV positive confirmed by: 2 positive rapid tests (Abbott-DetermineTM HIV-1/2 and Sensa (Seyama Solutions, SA)) or 1 positive rapid tests (Abbott-DetermineTM HIV-1/2 or Sensa (Seyama Solutions, SA)) and an additional confirmatory ELISA (Enzygnost anti-HIV-1/2 Plus) Is willing and likely to comply with the trial procedures Is prepared to grant authorized persons access to their medical records Exclusion Criteria: Has been in treatment for TB for more than 2 weeks Has a known MDR/XDR-TB Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response except for HIV treatment (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 an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis) 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 patient, 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 CFP-10 antigens Is pregnant, breastfeeding or intending to get pregnant 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 Denmark
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Keertan Dheda, MD
Organizational Affiliation
University of Cape Town Lung Institute (Pty) Ltd, South Africa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Cape Town Lung Institute (Pty) Ltd
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
26677940
Citation
Hoff ST, Peter JG, Theron G, Pascoe M, Tingskov PN, Aggerbeck H, Kolbus D, Ruhwald M, Andersen P, Dheda K. Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection. Eur Respir J. 2016 Mar;47(3):919-28. doi: 10.1183/13993003.01464-2015. Epub 2015 Dec 17.
Results Reference
derived
PubMed Identifier
23691171
Citation
Aggerbeck H, Giemza R, Joshi P, Tingskov PN, Hoff ST, Boyle J, Andersen P, Lewis DJ. Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection. PLoS One. 2013 May 14;8(5):e64215. doi: 10.1371/journal.pone.0064215. Print 2013.
Results Reference
derived

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A Trial of the C-Tb Skin Test, When Given Intradermally to Adult Patients Recently Diagnosed With Active Tuberculosis (TB)

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