Safety and Risk of Sensitisation of the rdESAT-6 + rCFP-10 Skin Test Following Repeated Intradermal Administration

Study Overview
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Brief Summary
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The primary objective is to assess the safety of three dose levels (0.01, 0.1 and 1.0 µg) of the rdESAT-6 + rCFP-10 skin test reagent when injected into healthy adults. The secondary objective is to assess the risk of sensitisation of 0.01 and 0.1 µg rdESAT-6 + rCFP-10 when injected twice with time intervals of 6 or 12 weeks to healthy adults.

Official Title
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An Open Phase I Clinical Trial on the Safety and Risk of Sensitisation by Escalating Doses and Repeated Injections of the rdESAT-6 + rCFP-10 Skin Test Reagent Following Intradermal Administration to Healthy Adults

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: rdESAT-6 + rCFP-10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed an informed consent Is willing and likely to be able to comply with the trial procedures Is female/male non-black adult ≥ 18 years and ≤ 55 years of age Is healthy according to a medical examination, medical history and laboratory investigations at inclusion Is prepared to grant authorized persons access to their medical records Exclusion Criteria: Has a history of tuberculosis or has had a known contact to a person with active tuberculosis Has a positive QuantiFERON-TB Gold In Tube test result at inclusion Laboratory parameters outside of normal range judged by principal investigator to be clinically significant and/or abnormal glucose or protein levels in a urine sample at inclusion Has been in treatment with a product which is likely to modify the immune response within 3 months prior to the day of inclusion (e.g., immunoglobulin, systemic corticosteroids, methotrexate, azathioprine, cyclosporine, infliximab or blood products) Has been vaccinated with a live vaccine within 6 months prior to the day of inclusion (e.g., MMR, yellow fever, or oral typhoid vaccines) Has a known congenital or acquired immune deficiency Has a disease affecting the lymphoid organs (e.g., Hodgkin's disease, lymphoma, leukemia, sarcoidosis) Is known to be infected with HIV, HBV or HCV Has a severe ongoing viral or bacterial infection that might affect the cell mediated immune response at inclusion Has a C-reactive protein (CRP) level > 50 mg/L Has severe scarring, burn, rash, eczema, psoriasis, or any other skin disease at or near the injection site(s) Has a condition in which repeated blood drawings pose more than minimal risk for the volunteer, such as haemophilia, other coagulation disorders, or significantly impaired venous access Is actively participating in another clinical trial or has participated in previous clinical trials investigating the rdESAT-6 skin test reagent Is pregnant according to urine pregnancy test at inclusion Is a female not willing to use contraceptives or is breastfeeding 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: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>two injections 0.01 µg rdESAT-6 + rCFP-10 (6 weeks interval) | Biological: rdESAT-6 + rCFP-10<br>* rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique<br>|
| Experimental: B<br>two injections 0.01 µg rdESAT-6 + rCFP-10 (12 weeks interval) | Biological: rdESAT-6 + rCFP-10<br>* rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique<br>|
| Experimental: C<br>two injections 0.1 µg rdESAT-6 + rCFP-10 (6 weeks interval) | Biological: rdESAT-6 + rCFP-10<br>* rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique<br>|
| Experimental: D<br>two injections 0.1 µg rdESAT-6 + rCFP-10 (12 weeks interval) | Biological: rdESAT-6 + rCFP-10<br>* rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique<br>|
| Experimental: E<br>one injection 1.0 µg rdESAT-6 + rCFP-10 | Biological: rdESAT-6 + rCFP-10<br>* rdESAT-6 + rCFP-10 skin test administered intradermally by the mantoux injection technique<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic adverse events with onset after the FIRST (0.01, 0.1 and 1.0 µg) or SECOND (0.01 and 0.1 µg) injection |  | onset between the first injection and 28 days after the second injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diameter of induration at the second injection site measured transversely to the long axis of the forearm |  | 72 hours after the second injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tuberculosis, diagnosis, ESAT-6, CFP-10, skin test, Skin test for the diagnosis of tuberculosis infection