Safety Study Investigating if Concomitant Injections of C-Tb and 2 T.U Tuberculin Affect Induration Responses (TESEC-07)

• To compare the size of induration of C-Tb and PPD RT 23 if injected alone or concomitantly in Tuberculosis infected patients (HIV positives and HIV negatives) [ Time Frame: Onset from the injection(s) to 28 days after the injections ] [ Designated as safety issue: No ]
• To assess if concomitant injections of C-Tb and PPD RT 23 influence the tests abilities to identify positive results of Tuberculosis in Tuberculosis infected patients [ Time Frame: Onset from the injection(s) to 28 days after the injections ] [ Designated as safety issue: No ]

• To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the in vitro QuantiFERON®TB Gold In Tube assay in blood collected immediately before application of the C-Tb skin test [ Time Frame: Onset from the injection(s) to 28 days after the injections ] [ Designated as safety issue: No ]
• To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the PPD RT 23 test [ Time Frame: Onset from the injection(s) to 28 days after the injections ] [ Designated as safety issue: No ]
• To assess the safety of C-Tb skin test by investigating laboratory safety parameters and assessing all adverse events (local and systemic) occurring within 28 days after administration of the C-Tb and/or PPD RT 23 tests [ Time Frame: Onset from the injection(s) to 28 days after the injections ] [ Designated as safety issue: Yes ]

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 induration at the injection site, while a negative test will leave no reactions.

The aim of this study is to address if the size of induration and the sensitivity of C-Tb is influenced by concomitant injections of C-Tb and Tuberculin. Furthermore, the intention is to evaluate the safety of C-Tb when injected alone or concomitantly with Tuberculin.

The TESEC-07 trial is a GCP double blind randomised controlled phase II/III trial investigating if concomitant injections of the diagnostic agents C-Tb and 2 T.U Tuberculin PPD RT 23 SSI affect the induration responses in combination with a safety assessment of C-Tb. TESEC-07 is a multi-centre trial and will be conducted in South Africa in patients recently diagnosed with TB comprising 360 HIV negative and 90 HIV positive adults allocated to 3 trial groups.

• A within group paired comparison of 0.1 μg/0.1 mL C-Tb and PPD RT 23 in 150 TB patients. The C-Tb and PPD RT 23 agents are given concomitantly to each volunteer in the RIGHT AND LEFT forearms according to a randomisation scheme.
• A group of 150 TB patients will only receive the C-Tb agent randomised to either RIGHT or LEFT forearm.
• A group of 150 TB patients will only receive the reference agent PPD RT 23 randomised to either RIGHT or LEFT forearm.

• Biological: C-Tb
  C-Tb is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
• Biological: Tuberculin PPD RT 23 SSI
  Tuberculin is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme
• Biological: C-Tb / Tuberculin PPD RT 23 SSI
  The C-Tb and Tuberculin agents are administered by the Mantoux injection technique to each volunteer in the RIGHT and LEFT forearm according to a double blind randomisation scheme

• Experimental: 0.1 µg C-Tb
  The C-Tb agent is given alone to volunteers in the RIGHT or LEFT forearm according to a double blind randomisation scheme
  Intervention: Biological: C-Tb
• Active Comparator: 2 T.U Tuberculin PPD RT 23 SSI
  The 2 T.U Tuberculin PPD RT 23 SSI agent is given alone to volunteers in the RIGHT or LEFT forearm according to a double blind randomisation scheme
  Intervention: Biological: Tuberculin PPD RT 23 SSI
• Experimental: 0.1 µg C-Tb / 2 T.U Tuberculin PPD
  The C-Tb and 2 T.U Tuberculin PPD RT 23 SSI agents are given concomitantly to volunteers in the RIGHT and LEFT forearms according to a double blind randomisation scheme
  Intervention: Biological: C-Tb / Tuberculin PPD RT 23 SSI

Inclusion Criteria (HIV Negative patients):

• Has signed an informed consent
• Aged 18 to 65 years

• Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
• Is HIV negative confirmed by 2 two rapid tests
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical record

Inclusion Criteria (HIV Positive patients):

• Has signed an informed consent
• Aged 18-65 years

• Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis

• Is HIV positive confirmed by:

  1. 2 positive rapid tests or
  2. 1 positive rapid tests and an additional confirmatory ELISA
• A CD4 count has been performed
• Is willing and likely to comply with the trial procedures
• Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

• Has been in treatment for TB for more than 2 weeks
• Has a known MDR/XDR-TB
• Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) except BCG vaccine
• Has been tuberculin (TST) tested < 12 months prior to the day of inclusion
• Is pregnant, breastfeeding or intending to get pregnant
• Is a female of child bearing potential not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
• Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
• 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 patient, 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 CFP-10 antigens
• Has a condition which in the opinion of the investigator is not suitable for participation in the study