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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A 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

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: C-Tb
* Biological: Tuberculin PPD RT 23 SSI
* Biological: C-Tb / Tuberculin PPD RT 23 SSI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (HIV Negative patients): Has signed an informed consent Aged 18 to 65 years Has been diagnosed with active pulmonary TB: has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or 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: has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or 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: 2 positive rapid tests or 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.1 µg C-Tb<br>The C-Tb agent is given alone to volunteers in the RIGHT or LEFT forearm according to a double blind randomisation scheme | Biological: C-Tb<br>* 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<br>|
| Active Comparator: 2 T.U Tuberculin PPD RT 23 SSI<br>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 | Biological: Tuberculin PPD RT 23 SSI<br>* Tuberculin is administered by the Mantoux injection technique to each volunteer in the RIGHT or LEFT forearm according to a double blind randomisation scheme<br>|
| Experimental: 0.1 µg C-Tb / 2 T.U Tuberculin PPD<br>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 | Biological: C-Tb / Tuberculin PPD RT 23 SSI<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | Onset from the injection(s) to 28 days after the injections | 
| 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 |  | Onset from the injection(s) to 28 days after the injections | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Onset from the injection(s) to 28 days after the injections | 
| To compare the C-Tb test's ability to identify positive results in Tuberculosis infected patients with the PPD RT 23 test |  | Onset from the injection(s) to 28 days after the injections | 
| 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 |  | Onset from the injection(s) to 28 days after the injections |