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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01631266
• Other study ID #: TESEC-06
• Secondary ID: 2011-005617-36
• Status: Completed
• Phase: Phase 3
• First received: June 28, 2012
• Last updated: April 16, 2015
• Start date: July 2012
• Est. completion date: October 2014

Study information

• Verified date: April 2015
• Source: Statens Serum Institut
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 979
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Weeks to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

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
• 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

Locations

Country	Name	City	State
Spain	Hospital Universitario de Cruces	Barakaldo	Basque Country
Spain	CAP Drassanes, Unitat de Prevenció i Control de Tuberculosi	Barcelona	Catalonia
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona	Catalonia
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalonia
Spain	Hospital del Mar	Barcelona	Catalonia
Spain	Hospital Mutua de Terrassa	Barcelona	Catalonia
Spain	Hospital San Joan De Deu	Barcelona	Catalonia
Spain	Hospital Vall d'Hebron	Barcelona	Catalonia
Spain	Public Health Agency of Barcelona	Barcelona	Catalonia
Spain	Hospital Universitario Lucus Augusti	Lugo	Galicia
Spain	Complexo Hospitalario de Pontevedra	Pontevedra	Galicia
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	Galicia
Spain	Complexo Hospitalario Universitario de Vigo	Vigo	Galicia

Sponsors (1)

Lead Sponsor	Collaborator
Statens Serum Institut

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate an increasing trend in C-Tb test positivity across the four study groups, with 'positivity' defined as an induration = 5 mm		Onset between the injections and 28 days after the injections	No
Secondary	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		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate a possible trend in C-Tb induration diameters across the four pre-specified MTb infection risk sub-groups		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate a possible trend in PPD RT23 SSI induration diameters across the four pre-specified MTb infection risk sub-groups		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate a possible trend in QuantiFERON Gold In-Tube results across four pre-specified MTb infection risk sub-groups		On the day of the injections	No
Secondary	To evaluate a possible trend in PPD RT23 SSI test positivity across four pre-specified MTb infection risk sub-groups		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate a possible trend in QuantiFERON Gold In-Tube test positivity across four pre-specified MTb infection risk sub-groups		On the day of the injections	No
Secondary	To evaluate the difference in sensitivity between C-Tb and QuantiFERON Gold In-Tube in the positive control group		From the day of injections to 2-3 days after the injections	No
Secondary	To evaluate the difference in specificity between C-Tb and QuantiFERON Gold In-Tube in the negative control group		From the day of injections to 2-3 days after the injections	No
Secondary	To evaluate the difference in sensitivity between C-Tb and PPD RT23 SSI in positive control group		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate the difference in specificity between C-Tb and PPD RT23 SSI in the negative control group		Onset between the injections and 28 days after the injections	No
Secondary	To compare the size of induration of C-Tb if injected alone or concomitantly with PPD RT23 SSI in negative control group		Onset between the injections and 28 days after the injections	No
Secondary	To compare the specificity of C-Tb if injected alone or concomitantly with PPD RT23 SSI, in the negative control group		Onset between the injections and 28 days after the injections	No
Secondary	To compare the diagnostic outcome of C-Tb to that of QuantiFERON Gold In-Tube using a latent class approach		From the day of injections to 2-3 days after the injections	No
Secondary	To compare the diagnostic outcome of C-Tb to that of PPD RT23 SSI using a latent class approach		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate the secondary analyses above (1-14) of C-Tb and PPD RT23 SSI using alternative cut-off values		Onset between the injections and 28 days after the injections	No
Secondary	To compare the diagnostic outcome of C-Tb and QuantiFERON Gold In-Tube stratified on the four study groups		From the day of injections to 2-3 days after the injections	No
Secondary	To compare the diagnostic outcome of C-Tb and PPD RT23 SSI stratified on the four study groups		Onset between the injections and 28 days after the injections	No
Secondary	To evaluate the clinical safety of C-Tb		Onset between the injections and 28 days after the injections	Yes
Secondary	To evaluate the clinical safety of PPD RT23 SSI		Onset between the injections and 28 days after the injections	Yes