A Contact Tracing Trial Comparing the Diagnostic Performance of C-Tb to QuantiFERON®-TB, in Combination With a Safety Assessment of C-Tb Versus Tuberculin PPD RT23 SSI

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Statens Serum Institut
Sponsor:
Information provided by (Responsible Party):
Statens Serum Institut
ClinicalTrials.gov Identifier:
NCT01631266
First received: June 28, 2012
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Tuberculosis
Biological: C-Tb
Biological: 2 T.U. Tuberculin PPD RT 23 SSI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Statens Serum Institut:

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 [ Time Frame: Onset between the injections and 28 days after the injections ] [ Designated as safety issue: No ]

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 [ Time Frame: Onset between the injections and 28 days after the injections ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate the clinical safety of C-Tb [ Time Frame: Onset between the injections and 28 days after the injections ] [ Designated as safety issue: Yes ]
  • To evaluate the clinical safety of PPD RT23 SSI [ Time Frame: Onset between the injections and 28 days after the injections ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 950
Study Start Date: July 2012
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.1 µg/0.1 mL C-Tb
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
Biological: C-Tb
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
Active Comparator: 2 T.U. Tuberculin PPD RT 23 SSI
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
Biological: 2 T.U. Tuberculin PPD RT 23 SSI
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

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.

  Eligibility

Ages Eligible for Study:   6 Weeks to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631266

Contacts
Contact: Bettine Borregaard, RN +45 3268 3416 BTG@ssi.dk
Contact: Erik Carp, M.Sc. +45 3268 8657 ECA@ssi.dk

Locations
Spain
Hospital Universitario de Cruces Recruiting
Barakaldo, Basque Country, Spain, 48903
Contact: Jose Villate, MD    +34 946006105    joseignacio.villatenavarro@osakidetza.net   
Principal Investigator: Jose Villate, MD         
Public Health Agency of Barcelona Recruiting
Barcelona, Catalonia, Spain, 08023
Contact: Joan Cayla, MD    +34 932384555    jcayla@aspb.es   
Principal Investigator: Joan Cayla, MD         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Catalonia, Spain, 08025
Contact: Virginia Pomar, MD    +34 935565624    vpomar@santpau.cat   
Principal Investigator: Virginia Pomar, MD         
Hospital del Mar Recruiting
Barcelona, Catalonia, Spain, 08003
Contact: Francesca Sanchez, MD    +34 2483246    psanchez@aspb.cat   
Principal Investigator: Francesca Sanchez, MD         
Hospital Clínic i Provincial de Barcelona Recruiting
Barcelona, Catalonia, Spain, 08036
Contact: Jose A. Martinez, MD    +34 93 2275400    jamarti@clinic.ub.es   
Principal Investigator: Jose A. Martinez, MD         
CAP Drassanes, Unitat de Prevenció i Control de Tuberculosi Recruiting
Barcelona, Catalonia, Spain, 08001
Contact: Maria Luisa de Souza, MD    +34 93 3012424    maludesouzagalvao@gmail.com   
Principal Investigator: Maria Luisa de Souza, MD         
Hospital Mutua de Terrassa Recruiting
Barcelona, Catalonia, Spain, 08221
Contact: Javier Martinez, MD    +34 937367020    xmartinez@mutuaterrassa.es   
Principal Investigator: Javier Martinez, MD         
Hospital Vall d'Hebron Recruiting
Barcelona, Catalonia, Spain, 08035
Contact: Jose Angel, MD    +34 934894214    jarodrig@vhebron.net   
Principal Investigator: Jose Angel, MD         
Hospital San Joan De Deu Recruiting
Barcelona, Catalonia, Spain, 08950
Contact: Antonio Noguera Julian, MD    +340639649777    ton@hsjdbcn.org   
Hospital Universitario Lucus Augusti Recruiting
Lugo, Galicia, Spain, 27004
Contact: Antonio Penas, MD    +34 982295129    Anton.Penas.Truque@sergas.es   
Principal Investigator: Antonio Penas, MD         
Complexo Hospitalario de Pontevedra Recruiting
Pontevedra, Galicia, Spain, 36071
Contact: Luis Anibarro, MD    +34 986807005    luis.anibarro.garcia@sergas.es   
Principal Investigator: Luis Anibarro, MD         
Complejo Hospitalario Universitario de Santiago Recruiting
Santiago de Compostela, Galicia, Spain, 15706
Contact: Victoria Tuñez, MD    +34 981 950 036    victoria.tunez.bastida@sergas.es   
Principal Investigator: Victoria Tuñez, MD         
Complexo Hospitalario Universitario de Vigo Recruiting
Vigo, Galicia, Spain, +34 981 950 036
Contact: Rafael Vázquez, MD    +34 650356111    Rafael.Vazquez.Gallardo@sergas.es   
Principal Investigator: Rafael Vázquez, MD         
Sponsors and Collaborators
Statens Serum Institut
Investigators
Principal Investigator: Joan Cayla, MD Public Health Agency of Barcelona
Study Chair: Henrik Aggerbeck, M. Sc. Statens Serum Institut
  More Information

No publications provided

Responsible Party: Statens Serum Institut
ClinicalTrials.gov Identifier: NCT01631266     History of Changes
Other Study ID Numbers: TESEC-06, 2011-005617-36
Study First Received: June 28, 2012
Last Updated: February 17, 2014
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 24, 2014