Clinical trial NCT02336542: Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
Official title: For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6 - CFP10 Dose of Certain Phase IIb Clinical Research
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: diagnosis of Tuberculosis
ESAT6
CFP10
skin test
diagnostic test
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Public Health Clinical Center
name: Tianjin Haihe Hospital
name: Wuhan Institute for Tuberculosis Control
name: Proswell Medical Corporation
name: Air Force Military Medical University, China
First posted: 2015-01-13
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: Firstly,96 TB(Tuberculosis ) subjects which meet the standard respectively are divided into different groups through a randomized, blind methods.

1. ESAT6-CFP10 （5μg/ml）in left arm；
2. ESAT6-CFP10 （5μg/ml）in right arm；
3. ESAT6-CFP10 （10μg/ml）in left arm；
4. 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 .

Eligibility criteria: 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.

Primary outcomes:
measure: the diameter of induraton or redness within 72 hours after intradermal injection with ESAT6-CFP10 in TB patients
timeFrame: within 72h after injection
measure: the proportion of positive reaction within 72 hours after administered intradermally TB-PPD in TB patient
timeFrame: within 72h after injection
measure: Immune response of of ESAT6-CFP10 from the size of induration OR redness in non-TB patients with lung diseases
timeFrame: within 72h after injection
measure: The proportion of positive reaction after receiving specificity γ-IFN test in TB subjects and non-TB subjects with lung disease
timeFrame: before administered intradermally
measure: the proportion of positive reaction within 72 hours after intradermal injection with TB-PPD in non-TB patients with lung diseases
timeFrame: within 72h after injection
Secondary outcomes:
measure: the occurrence of adverse events within 72 hours after injection in TB subjects and non-TB subjects with lung disease
timeFrame: within 72h after injection two drugs
measure: the consistency between ESAT6-CFP10 and TB-PPD in TB subjects and non-TB subjects with lung disease
timeFrame: within 72h after injection
measure: the consistency between ESAT6-CFP10 and γ-IFN in TB subjects and non-TB subjects with lung disease
timeFrame: within 72h after injection
measure: the consistency between TB-PPD and γ-IFN in TB subjects and non-TB subjects with lung disease
timeFrame: within 72h after injection
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Public Health Clinical Center
name: Shuihua Lu, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Haihe Hospital
name: Qi Wu, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuhan Insititute for Tuberculosis Control
name: Weihua Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Xu M, Lu W, Li T, Li J, Du W, Wu Q, Liu Q, Yuan B, Lu J, Ding X, Li F, Liu M, Chen B, Pu J, Zhang R, Xi X, Zhou R, Mei Z, Du R, Tao L, Martinez L, Lu S, Wang G, Zhu F. Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials. Clin Infect Dis. 2022 Mar 1;74(4):668-677. doi: 10.1093/cid/ciab472.