search
Back to results

Comparison of Diagnostic Performance of C-Tb to QuantiFERON®-TB, in Combination With a Safety Assessment of C-Tb vs Tuberculin PPD RT23 SSI

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
C-Tb
2 T.U. 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

Eligibility Criteria

6 Weeks - 65 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Can comply with one of the following groups:

    1. Negative control group: Must have no history of exposure to a TB index case, and have no signs or symptoms of TB
    2. Positive control group: Confirmed TB disease within the last 3 years by sputum smear microscopy and/or Culture, Gene Xpert or PCR
    3. Close contact group: Must be in close contact with a pulmonary smear positive TB index case for more than 6 hours/day for at least five days
    4. Occasional contact group: Must be in contact with a pulmonary sputum smear positive TB index case between 6 hours/week and 6 hours/day
  2. Is between 6 weeks - 65 years of age
  3. Participant, parent or legal guardian has provided signed informed consent
  4. Is willing and likely to comply with the trial procedures
  5. Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

  1. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. Mumps Measles Rubella (MMR), yellow fever, oral typhoid vaccines)
  2. Has been tuberculin tested less than 12 months prior to the day of inclusion
  3. Is pregnant, breastfeeding or intending to get pregnant within the trial period
  4. Is a female of child bearing potential (12 years of age or older having had their first menstruation) not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures within the trial period
  5. Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
  6. Has a current skin condition which interferes with the reading of the C-Tb and Tuberculin PPD RT23 SSI e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
  7. Has a condition where blood drawings pose more than minimal risk for the participant, such as haemophilia, other coagulation disorders, or significantly impaired venous access
  8. Current participation in another clinical trial with an investigational or non investigational drug or device, which in the opinion of investigator may interfere with this trial drug
  9. Has participated in previous clinical trials investigating injections with ESAT-6 and/or CFP-10 antigens
  10. Has a condition which in the opinion of the investigator is not suitable for participation in the trial

Sites / Locations

  • Hospital Universitario de Cruces
  • CAP Drassanes, Unitat de Prevenció i Control de Tuberculosi
  • Hospital del Mar
  • Public Health Agency of Barcelona
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Vall d'Hebron
  • Hospital Clínic i Provincial de Barcelona
  • Hospital Mutua de Terrassa
  • Hospital San Joan De Deu
  • Hospital Universitario Lucus Augusti
  • Complexo Hospitalario de Pontevedra
  • Complejo Hospitalario Universitario de Santiago
  • Complexo Hospitalario Universitario de Vigo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

0.1 µg/0.1 mL C-Tb

2 T.U. Tuberculin PPD RT 23 SSI

Arm Description

The C-Tb and 2 T.U. 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 T.U. 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

To demonstrate an increasing trend in C-Tb test positivity across the four study groups, with 'positivity' defined as an induration ≥ 5 mm

Secondary Outcome Measures

To demonstrate a significantly lower response rate of C-Tb as compared to that of PPD RT23 SSI in the BCG vaccinated participants in the negative control group, with response defined as any induration (> 1mm) for both agents
To evaluate a possible trend in C-Tb induration diameters across the four pre-specified MTb infection risk sub-groups
To evaluate a possible trend in PPD RT23 SSI induration diameters across the four pre-specified MTb infection risk sub-groups
To evaluate a possible trend in QuantiFERON Gold In-Tube results across four pre-specified MTb infection risk sub-groups
To evaluate a possible trend in PPD RT23 SSI test positivity across four pre-specified MTb infection risk sub-groups
To evaluate a possible trend in QuantiFERON Gold In-Tube test positivity across four pre-specified MTb infection risk sub-groups
To evaluate the difference in sensitivity between C-Tb and QuantiFERON Gold In-Tube in the positive control group
To evaluate the difference in specificity between C-Tb and QuantiFERON Gold In-Tube in the negative control group
To evaluate the difference in sensitivity between C-Tb and PPD RT23 SSI in positive control group
To evaluate the difference in specificity between C-Tb and PPD RT23 SSI in the negative control group
To compare the size of induration of C-Tb if injected alone or concomitantly with PPD RT23 SSI in negative control group
To compare the specificity of C-Tb if injected alone or concomitantly with PPD RT23 SSI, in the negative control group
To compare the diagnostic outcome of C-Tb to that of QuantiFERON Gold In-Tube using a latent class approach
To compare the diagnostic outcome of C-Tb to that of PPD RT23 SSI using a latent class approach
To evaluate the secondary analyses above (1-14) of C-Tb and PPD RT23 SSI using alternative cut-off values
To compare the diagnostic outcome of C-Tb and QuantiFERON Gold In-Tube stratified on the four study groups
To compare the diagnostic outcome of C-Tb and PPD RT23 SSI stratified on the four study groups
To evaluate the clinical safety of C-Tb
To evaluate the clinical safety of PPD RT23 SSI

Full Information

First Posted
June 28, 2012
Last Updated
April 16, 2015
Sponsor
Statens Serum Institut
search

1. Study Identification

Unique Protocol Identification Number
NCT01631266
Brief Title
Comparison of Diagnostic Performance of C-Tb to QuantiFERON®-TB, in Combination With a Safety Assessment of C-Tb vs Tuberculin PPD RT23 SSI
Official Title
A Phase III Contact Tracing Trial Comparing the Diagnostic Performance of C-Tb to QuantiFERON®-TB Gold In-Tube, in Combination With a Double Blind Randomized Split Body Safety Assessment of C-Tb Versus 2 T.U. Tuberculin PPD RT23 SSI
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (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. We are investigating a new skin test named C-Tb. Like the current tuberculin skin test (PPD), the C-Tb test is injected just under the skin and will, when positive, show 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 volunteers. The volunteers are divided into four groups: Negative control group: Must have no history of exposure to a person with tuberculosis disease. Occasional contact: Must be in contact with a person with tuberculosis disease between 6 hours/week and 6 hours/day Close contact: Must be in close contact with a person with tuberculosis disease for more than 6 hours/day for at least five days Positive control group: Must have a confirmed tuberculosis disease within the last 3 years. The goals of this clinical trial are: To compare the C-Tb test to a blood test, the QuantiFERON test. To compare the C-Tb test to the PPD test that is currently being used. To assess the safety of the C-Tb test.
Detailed Description
The TESEC-06 trial is an open comparison of the diagnostics performance of C-Tb compared to QuantiFERON®-TB Gold In-Tube, in combination with a double-blind randomized split-body safety assessment of C-Tb versus Tuberculin PPD RT23 SSI. The trial is designed to address the fundamental issue that in the diagnosis of latent tuberculosis (TB) infection, no gold standard exists. Thus, no existing test for latent TB is 100 % sensitive and specific - including the Tuberculin PPD RT23 SSI and QuantiFERON®-TB Gold In-Tube. This will be addressed by evaluating C-Tb positive response rates in 4 groups defined by their estimated risk of infection with MTb. The groups will consist of paediatric and adult participants selected as being either occasional or close contacts to an active pulmonary TB case. In addition a group of confirmed TB cases and a group of participants with no history of exposure to MTb will be included as control groups. 50 participants in the negative control group will be tested with C-Tb alone in order to evaluate whether concomitant administration of C-Tb and Tuberculin PPD RT23 SSI could conceivably result in larger or smaller areas of induration to one or both tests as a result of expanding the clone of sensitised T-cells i.e. since Tuberculin PPD RT23 SSI includes among several other antigens ESAT-6 and CFP-10 and C-Tb also contains both these antigens.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
979 (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 T.U. 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 T.U. Tuberculin PPD RT 23 SSI
Arm Type
Active Comparator
Arm Description
The C-Tb and 2 T.U. 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
Intervention Description
The C-Tb agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
Intervention Type
Biological
Intervention Name(s)
2 T.U. Tuberculin PPD RT 23 SSI
Intervention Description
The 2 T.U. Tuberculin PPD RT 23 SSI agent is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
Primary Outcome Measure Information:
Title
To demonstrate an increasing trend in C-Tb test positivity across the four study groups, with 'positivity' defined as an induration ≥ 5 mm
Time Frame
Onset between the injections and 28 days after the injections
Secondary Outcome Measure Information:
Title
To demonstrate a significantly lower response rate of C-Tb as compared to that of PPD RT23 SSI in the BCG vaccinated participants in the negative control group, with response defined as any induration (> 1mm) for both agents
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate a possible trend in C-Tb induration diameters across the four pre-specified MTb infection risk sub-groups
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate a possible trend in PPD RT23 SSI induration diameters across the four pre-specified MTb infection risk sub-groups
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate a possible trend in QuantiFERON Gold In-Tube results across four pre-specified MTb infection risk sub-groups
Time Frame
On the day of the injections
Title
To evaluate a possible trend in PPD RT23 SSI test positivity across four pre-specified MTb infection risk sub-groups
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate a possible trend in QuantiFERON Gold In-Tube test positivity across four pre-specified MTb infection risk sub-groups
Time Frame
On the day of the injections
Title
To evaluate the difference in sensitivity between C-Tb and QuantiFERON Gold In-Tube in the positive control group
Time Frame
From the day of injections to 2-3 days after the injections
Title
To evaluate the difference in specificity between C-Tb and QuantiFERON Gold In-Tube in the negative control group
Time Frame
From the day of injections to 2-3 days after the injections
Title
To evaluate the difference in sensitivity between C-Tb and PPD RT23 SSI in positive control group
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate the difference in specificity between C-Tb and PPD RT23 SSI in the negative control group
Time Frame
Onset between the injections and 28 days after the injections
Title
To compare the size of induration of C-Tb if injected alone or concomitantly with PPD RT23 SSI in negative control group
Time Frame
Onset between the injections and 28 days after the injections
Title
To compare the specificity of C-Tb if injected alone or concomitantly with PPD RT23 SSI, in the negative control group
Time Frame
Onset between the injections and 28 days after the injections
Title
To compare the diagnostic outcome of C-Tb to that of QuantiFERON Gold In-Tube using a latent class approach
Time Frame
From the day of injections to 2-3 days after the injections
Title
To compare the diagnostic outcome of C-Tb to that of PPD RT23 SSI using a latent class approach
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate the secondary analyses above (1-14) of C-Tb and PPD RT23 SSI using alternative cut-off values
Time Frame
Onset between the injections and 28 days after the injections
Title
To compare the diagnostic outcome of C-Tb and QuantiFERON Gold In-Tube stratified on the four study groups
Time Frame
From the day of injections to 2-3 days after the injections
Title
To compare the diagnostic outcome of C-Tb and PPD RT23 SSI stratified on the four study groups
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate the clinical safety of C-Tb
Time Frame
Onset between the injections and 28 days after the injections
Title
To evaluate the clinical safety of PPD RT23 SSI
Time Frame
Onset between the injections and 28 days after the injections

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Can comply with one of the following groups: Negative control group: Must have no history of exposure to a TB index case, and have no signs or symptoms of TB Positive control group: Confirmed TB disease within the last 3 years by sputum smear microscopy and/or Culture, Gene Xpert or PCR Close contact group: Must be in close contact with a pulmonary smear positive TB index case for more than 6 hours/day for at least five days Occasional contact group: Must be in contact with a pulmonary sputum smear positive TB index case between 6 hours/week and 6 hours/day Is between 6 weeks - 65 years of age Participant, parent or legal guardian has provided signed informed consent 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 vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. Mumps Measles Rubella (MMR), yellow fever, oral typhoid vaccines) Has been tuberculin tested less than 12 months prior to the day of inclusion Is pregnant, breastfeeding or intending to get pregnant within the trial period Is a female of child bearing potential (12 years of age or older having had their first menstruation) not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures within the trial period 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 C-Tb and Tuberculin PPD RT23 SSI 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 participant, such as haemophilia, other coagulation disorders, or significantly impaired venous access Current participation in another clinical trial with an investigational or non investigational drug or device, which in the opinion of investigator may interfere with this trial drug Has participated in previous clinical trials investigating injections with ESAT-6 and/or CFP-10 antigens Has a condition which in the opinion of the investigator is not suitable for participation in the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joan Cayla, MD
Organizational Affiliation
Public Health Agency of Barcelona
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Henrik Aggerbeck, M. Sc.
Organizational Affiliation
Statens Serum Institut
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Universitario de Cruces
City
Barakaldo
State/Province
Basque Country
ZIP/Postal Code
48903
Country
Spain
Facility Name
CAP Drassanes, Unitat de Prevenció i Control de Tuberculosi
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08001
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08003
Country
Spain
Facility Name
Public Health Agency of Barcelona
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08023
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínic i Provincial de Barcelona
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Mutua de Terrassa
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08221
Country
Spain
Facility Name
Hospital San Joan De Deu
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitario Lucus Augusti
City
Lugo
State/Province
Galicia
ZIP/Postal Code
27004
Country
Spain
Facility Name
Complexo Hospitalario de Pontevedra
City
Pontevedra
State/Province
Galicia
ZIP/Postal Code
36071
Country
Spain
Facility Name
Complejo Hospitalario Universitario de Santiago
City
Santiago de Compostela
State/Province
Galicia
ZIP/Postal Code
15706
Country
Spain
Facility Name
Complexo Hospitalario Universitario de Vigo
City
Vigo
State/Province
Galicia
ZIP/Postal Code
+34 981 950 036
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
28159608
Citation
Ruhwald M, Aggerbeck H, Gallardo RV, Hoff ST, Villate JI, Borregaard B, Martinez JA, Kromann I, Penas A, Anibarro LL, de Souza-Galvao ML, Sanchez F, Rodrigo-Pendas JA, Noguera-Julian A, Martinez-Lacasa X, Tunez MV, Fernandez VL, Millet JP, Moreno A, Cobos N, Miro JM, Roldan L, Orcau A, Andersen P, Cayla JA; TESEC Working Group. Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon gamma release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial. Lancet Respir Med. 2017 Apr;5(4):259-268. doi: 10.1016/S2213-2600(16)30436-2. Epub 2017 Feb 1.
Results Reference
derived

Learn more about this trial

Comparison of Diagnostic Performance of C-Tb to QuantiFERON®-TB, in Combination With a Safety Assessment of C-Tb vs Tuberculin PPD RT23 SSI

We'll reach out to this number within 24 hrs