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

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.

Inclusion criteria

• Has signed an informed consent
• Aged 18 to 65 years
• Is known to be BCG vaccinated (documented in medical files and/or by the presence of a BCG scar)
• Is healthy according to a medical examination and medical history at screening
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical records

Exclusion criteria

• Has a history of tuberculosis or has been in close contact to a person with active tuberculosis within 5 years from trial inclusion
• Has a positive QuantiFERON®-TB Gold In-Tube assay at inclusion
• Laboratory parameters outside of normal range judged by site investigator to be clinically significant
• 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)
• Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines)
• Has been vaccinated with BCG < 6 months prior to the day of inclusion
• Has been tuberculin (TST) tested < 6 months prior to the day of inclusion
• Has a known congenital or acquired immune deficiency
• Has an active disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
• Is infected with HIV
• 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
• 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
• 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
• Has participated in previous clinical trials investigating the ESAT-6 and/or CPP-10 antigens
• Is pregnant, breast-feeding or intending to get pregnant
• Is a female not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures
• Has a history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the 12 months preceding Visit 1
• Has a positive urine drug screen at Visit 1 and Visit 2 (i.e., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates)
• 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]
• Has a condition which in the opinion of the investigator is not suitable for participation in the study