Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

Study Overview
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Brief Summary
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96 TB subjects and 96 non-TB subjects with lung disease who all meet the standard are divided into different groups through a randomized, blind methods.Every subject inject intradermally ESAT6-CFP10 and TB-PPD in different arms of the same person.Specific γ- IFN(gamma interferon) detection is needed before the injection.Evaluate the sensitivity (positive coincidence rate) ,the specificity (negative coincidence rate) and the coincidence rate of ESAT6-CFP10 in the tuberculosis patients and non-tuberculosis patients with lung diseases, and determine the optimal dose of ESAT6-CFP10 for clinical auxiliary diagnosis of tuberculosis.

Detailed Description
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Firstly,96 TB(Tuberculosis ) subjects which meet the standard respectively are divided into different groups through a randomized, blind methods. ESAT6-CFP10 （5μg/ml）in left arm； ESAT6-CFP10 （5μg/ml）in right arm； ESAT6-CFP10 （10μg/ml）in left arm； ESAT6-CFP10 （10μg/ml）in right arm； Inject intradermally ESAT6-CFP10 and TB-PPD(tuberculin purified protein derivative ) in different arms of the same subject.For each of the participants in this clinical research, this study uniform that left arm inject a drug(ESAT6-CFP10 or TB - PPD) first, observe 30 min and no no obvious adverse reaction ,then another drug(ESAT6-CFP10 or TB - PPD) inject in right arm. We need draw blood to detect specific γ- IFN before the injection.Observe and record the vital signs (breathing, heart rate, blood pressure and temperature),the skin reaction diameter of injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events. Secondly, 96 non-TB subjects with lung disease are divided into different groups and the procedure are as the same as 96 TB subjects above . Finally,we evaluate the sensitivity (positive coincidence rate) ,the specificity (negative coincidence rate) and the coincidence rate of ESAT6-CFP10 in the TB patients and non-tuberculosis patients with lung diseases,determine the optimal dose of ESAT6-CFP10 for clinical auxiliary diagnosis of tuberculosis,and further evaluate the safety of ESAT6-CFP10 for the clinical auxiliary diagnosis of tuberculosis .

Official Title
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For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6 - CFP10 Dose of Certain Phase IIb Clinical Research

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm
* Biological: 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm
* Biological: 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm
* Biological: 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria of TB (tuberculosis ) subjects: Diagnosis TB ; 18 to 65 years ; Consent and signed informed consent forms(ICF) ; Comply with follow-up . Exclusion Criteria of TB (tuberculosis ) subjects: advanced cancer, diabetes,copd in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc ; Taking part in other clinical or within 3 months involved in any other clinical; histories of allergy ; in pregnancy or lactation; In a mental illness ; Any conditions affect the trial evaluation. Inclusion Criteria of Non-tuberculosis subjects with lung disease : Diagnosis non-tuberculosis subjects with lung disease ; 18 to 65 years ; Consent and signed signed informed consent forms(ICF) ; Comply with follow-up . Exclusion Criteria of Non-tuberculosis subjects with lung disease : advanced cancer, diabetes,copd in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc ; Taking part in other clinical or within 3 months involved in any other clinical; histories of allergy; in pregnancy or lactation; In a mental illness ; Any conditions may affect the trial evaluation.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TB subjects<br>96 TB subjects are divided into four groups average .24 TB subjects are injected 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm. | Biological: 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm<br>* TB subjects and non-TB subjects with lung disease inject 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm respectively. Two drug must use at the same person and different arm.<br>Biological: 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm<br>* TB subjects and non-TB subjects with lung disease inject 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm respectively. Two drug must use at the same person and different arm.<br>Biological: 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm<br>* TB subjects and non-TB subjects with lung disease inject 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm respectively. Two drug must use at the same person and different arm.<br>Biological: 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm<br>* TB subjects and non-TB subjects with lung disease inject 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm respectively. Two drug must use at the same person and different arm.<br>|
| Active Comparator: non-TB subjects with lung disease<br>96 non-TB subjects with lung disease are divided into four groups average .24 TB subjects are injected 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm. | Biological: 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm<br>* TB subjects and non-TB subjects with lung disease inject 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm respectively. Two drug must use at the same person and different arm.<br>Biological: 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm<br>* TB subjects and non-TB subjects with lung disease inject 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm respectively. Two drug must use at the same person and different arm.<br>Biological: 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm<br>* TB subjects and non-TB subjects with lung disease inject 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm respectively. Two drug must use at the same person and different arm.<br>Biological: 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm<br>* TB subjects and non-TB subjects with lung disease inject 10μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm respectively. Two drug must use at the same person and different arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the diameter of induraton or redness within 72 hours after intradermal injection with ESAT6-CFP10 in TB patients | we measure the size 15min,24h,48h,72h after administered intradermally ESAT6-CFP10 | within 72h after injection | 
| the proportion of positive reaction within 72 hours after administered intradermally TB-PPD in TB patient | we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD | within 72h after injection | 
| Immune response of of ESAT6-CFP10 from the size of induration OR redness in non-TB patients with lung diseases | we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD | within 72h after injection | 
| The proportion of positive reaction after receiving specificity γ-IFN test in TB subjects and non-TB subjects with lung disease |  | before administered intradermally | 
| the proportion of positive reaction within 72 hours after intradermal injection with TB-PPD in non-TB patients with lung diseases | we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD | within 72h after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the occurrence of adverse events within 72 hours after injection in TB subjects and non-TB subjects with lung disease |  | within 72h after injection two drugs | 
| the consistency between ESAT6-CFP10 and TB-PPD in TB subjects and non-TB subjects with lung disease |  | within 72h after injection | 
| the consistency between ESAT6-CFP10 and γ-IFN in TB subjects and non-TB subjects with lung disease |  | within 72h after injection | 
| the consistency between TB-PPD and γ-IFN in TB subjects and non-TB subjects with lung disease |  | within 72h after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESAT6, diagnosis of Tuberculosis, CFP10, skin test, diagnostic test