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

Condition(s) targeted: Tuberculosis

Intervention: C-Tb (Biological); 2 T.U. Tuberculin PPD RT 23 SSI (Biological)

Phase: Phase 3

Status: Recruiting

Sponsored by: Statens Serum Institut

Official(s) and/or principal investigator(s):
Joan Cayla, MD, Principal Investigator, Affiliation: Public Health Agency of Barcelona
Henrik Aggerbeck, M. Sc., Study Chair, Affiliation: Statens Serum Institut

Overall contact:
Bettine Borregaard, RN, Phone: +45 3268 3416, Email: BTG@ssi.dk

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.

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

Primary outcome:

The specificity of C-Tb compared to that of QuantiFERON®-TB Gold In-Tube

The specificity of C-Tb compared to that of Tuberculin PPD RT23 SSI

The sensitivity of C-Tb compared to that of QuantiFERON®-TB Gold In-Tube

The sensitivity of C-Tb compared to that of Tuberculin PPD RT23 SSI

Secondary outcome:

Response ratios for C-Tb, QuantiFERON®-TB Gold In-Tube and Tuberculin PPD RT23 SSI in 4 groups defined by estimated risk of infection with MTb.

The diameter of induration at the C-Tb injection site measured transversely to the long axis of the forearm at 2 to 3 days after intradermal administration of C-Tb

The diameter of induration at the Tuberculin PPD RT23 SSI injection site measured transversely to the long axis of the forearm at 2 to 3 days after intradermal administration of Tuberculin PPD RT23 SSI

All adverse events (AE) occurring within 28 days after intradermal administration of C-Tb and Tuberculin PPD RT23 SSI

Laboratory safety parameters: hematology and biochemistry in participants ≥ 5 years of age

Injection site adverse reactions within 2 to 3 days after intradermal administration of C-Tb and Tuberculin PPD RT23 SSI

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.

Primary Objectives:

- To compare the diagnostic performance of C-Tb to that of QuantiFERON®-TB Gold In-Tube

- To compare the diagnostic performance of C-Tb to that of Tuberculin PPD RT23 SSI

- To assess the safety of C-Tb

Secondary Objectives:

• To assess the diagnostic outcome of C-Tb, QuantiFERON®-TB Gold In-Tube and Tuberculin PPD RT23 SSI between and within 4 groups defined by estimated risk of infection with M. tuberculosis (MTb).

Minimum age: 6 Weeks. Maximum age: 65 Years. Gender(s): Both.

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

Bettine Borregaard, RN, Phone: +45 3268 3416, Email: BTG@ssi.dk

Hospital Universitario de Cruces, Barakaldo, Basque Country 48903, Spain; Recruiting
Jose Villate, MD, Phone: +34 946006105, Email: joseignacio.villatenavarro@osakidetza.net
Jose Villate, MD, Principal Investigator

Public Health Agency of Barcelona, Barcelona, Catalonia 08023, Spain; Recruiting
Joan Cayla, MD, Phone: +34 932384555, Email: jcayla@aspb.es
Joan Cayla, MD, Principal Investigator

Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia 08025, Spain; Recruiting
Virginia Pomar, MD, Phone: +34 935565624, Email: vpomar@santpau.cat
Virginia Pomar, MD, Principal Investigator

CAP Drassanes, Unitat de Prevenció i Control de Tuberculosi, Barcelona, Catalonia 08001, Spain; Recruiting
Maria Luisa de Souza, MD, Phone: +34 93 3012424, Email: maludesouzagalvao@gmail.com
Maria Luisa de Souza, MD, Principal Investigator

Hospital Clínic i Provincial de Barcelona, Barcelona, Catalonia 08036, Spain; Recruiting
Jose A. Martinez, MD, Phone: +34 93 2275400, Email: jamarti@clinic.ub.es
Jose A. Martinez, MD, Principal Investigator

Hospital del Mar, Barcelona, Catalonia 08003, Spain; Recruiting
Francesca Sanchez, MD, Phone: +34 2483246, Email: psanchez@aspb.cat
Francesca Sanchez, MD, Principal Investigator

Hospital Mutua de Terrassa, Barcelona, Catalonia 08221, Spain; Recruiting
Javier Martinez, MD, Phone: +34 937367020, Email: xmartinez@mutuaterrassa.es
Javier Martinez, MD, Principal Investigator

Hospital Vall d'Hebron, Barcelona, Catalonia 08035, Spain; Recruiting
Jose Angel, MD, Phone: +34 934894214, Email: jarodrig@vhebron.net
Jose Angel, MD, Principal Investigator

Hospital Universitario Lucus Augusti, Lugo, Galicia 27004, Spain; Recruiting
Antonio Penas, MD, Phone: +34 982295129, Email: Anton.Penas.Truque@sergas.es
Antonio Penas, MD, Principal Investigator

Complexo Hospitalario de Pontevedra, Pontevedra, Galicia 36071, Spain; Recruiting
Luis Anibarro, MD, Phone: +34 986807005, Email: luis.anibarro.garcia@sergas.es
Luis Anibarro, MD, Principal Investigator

Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Galicia 15706, Spain; Recruiting
Victoria Tuñez, MD, Phone: +34 981 950 036, Email: victoria.tunez.bastida@sergas.es
Victoria Tuñez, MD, Principal Investigator

Complexo Hospitalario Universitario de Vigo, Vigo, Galicia +34 981 950 036, Spain; Recruiting
Rafael Vázquez, MD, Phone: +34 650356111, Email: Rafael.Vazquez.Gallardo@sergas.es
Rafael Vázquez, MD, Principal Investigator

Starting date: July 2012
Last updated: January 18, 2013