A Trial of the C-Tb Skin Test, When Given Intradermally to Healthy Volunteers Previously Vaccinated With BCG

Tuberculosis Clinical Trial

— TESEC-03  

Official title:

A Phase IIa Specificity Trial of the Diagnostic Agent C-Tb, When Given Intradermally by the Mantoux Technique to Healthy Volunteers Previously Vaccinated With BCG

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01242475
• Other study ID #: TESEC-03
• Secondary ID: 2009-017296-17
• Status: Completed
• Phase: Phase 2
• First received: November 16, 2010
• Last updated: January 18, 2013
• Start date: April 2011
• Est. completion date: November 2011

Study information

• Verified date: January 2013
• Source: Statens Serum Institut
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

A new, more specific skin test to detect tuberculosis has been developed by Statens Serum Institut in Denmark. The new skin test is named C-Tb and like the current Tuberculin a positive test result will show as redness and/or swelling at the injection site, while a negative test will leave no reactions.

The aim of this study is to test the C-Tb skin test in healthy adults previously BCG vaccinated to determine if healthy non tuberculosis infected individuals has a truly negative test result (this is called determining the specificity of the skin test). To be able to compare the new skin test with the current Tuberculin skin test volunteers will be injected with both the C-Tb and the TST skin test.

Description:

The trial is designed to investigate the specificity of C-Tb under various definitions of cut-off 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 the 2 T.U. Tuberculin PPD in the other arm).

The C-Tb and 2 T.U. Tuberculin PPD agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearm according to a double blind randomisation scheme.

The primary objective of the trial is to assess the specificity 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 negative outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to healthy BCG vaccinated adults The specificity of the C-Tb test is defined as the relative frequency of subjects in a healthy population (i.e., no exposure to MTb) who have an induration response < cut-off after a C-Tb test.

Similarly the sensitivity is defined as the relative frequency of patients with an induration response ≥ cut-off in TB patients.

An optimal cut-off point of being infected will be determined by combing the results from the present specificity study with those from a parallel sensitivity study in patients recently diagnosed with TB.

The secondary objectives of the trial are 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 and 28 days after the injections of the skin test agents using the QuantiFERON®-TB Gold In-Tube assay and finally to record all adverse events occurring within 28 days after application of the agents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Has signed an informed consent

2. Aged 18 to 65 years

3. Is known to be BCG vaccinated (documented in medical files and/or by the presence of a BCG scar)

4. Is healthy according to a medical examination and medical history at screening

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 a history of tuberculosis or has been in close contact to a person with active tuberculosis within 5 years from trial inclusion

2. Has a positive QuantiFERON®-TB Gold In-Tube assay at inclusion

3. Laboratory parameters outside of normal range judged by site investigator to be clinically significant

4. Has within 3 months prior to the day of inclusion been in treatment with a product which is likely to modify the immune response (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine or blood products)

5. Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)

6. Has been vaccinated with BCG < 6 months prior to the day of inclusion

7. Has been tuberculin (TST) tested < 6 months prior to the day of inclusion

8. Has a known congenital or acquired immune deficiency

9. Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)

10. Is infected with HIV

11. 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

12. Has a condition where blood drawings pose more than minimal risk for the volunteer, such as haemophilia, other coagulation disorders, or significantly impaired venous access

13. 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

14. Has participated in previous clinical trials investigating the ESAT-6 and/or CPP-10 antigens

15. Is pregnant, breast-feeding or intending to get pregnant

16. Is a female not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures

17. Has a history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1

18. Has a positive urine drug screen at Visit 1 and Visit 2 (i.e., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates)

19. Has a positive alcohol breath test at Visit 1 and Visit 2. [NOTE: subjects must be told to avoid consumption of alcoholic beverages for at least 24 hours prior to attending the Centre]

20. Has a condition which in the opinion of the investigator is not suitable for participation in the study

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 forearms according to a double blind randomisation scheme
• 2 TU Tuberculin PPD RT 23 SSI
The 2TU 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

Locations

Country	Name	City	State
United Kingdom	Surrey Clinical Research Centre, University of Surrey	Surrey	Guildford, Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Statens Serum Institut

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		From injections to 2-3 days after application of the agents	No
Secondary	Injection site adverse reactions within 28 days after application of the agents		Onset between the injections and 28 days after the injections	Yes
Secondary	All adverse events occurring within 28 days after application of the agents		Onset between the injections and 28 days after the injections	Yes
Secondary	Laboratory safety parameters of haematology and biochemistry		Onset between the injections and 28 days after the injections	Yes
Secondary	In vitro IFN-? response as measured by the QuantiFERON®-TB Gold In-Tube assay from blood samples taken at screening and 28 days after the injections of the skin test agents		Onset between the injections and 28 days after the injections	No