Clinical trial NCT02623556: Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen
Official title: For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6 - CFP10 Dose of Certain Phase III Clinical Research
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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: Air Force Military Medical University, China
name: Proswell Medical Corporation
name: Wuhan Institute for Tuberculosis Control
name: Beijing Chest Hospital
name: Wuxi Hospital for Infectious Diseases
name: First Affiliated Hospital of Chongqing Medical University
name: Fuzhou Pulmonary Hospital of Fujian
name: Zhenjiang Third People's Hospital
name: Anhui Provincial Hospital
name: Shenzhen Third People's Hospital
First posted: 2015-12-07
Enrollment: 1090
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: 720 cases TB (Tuberculosis patients) participants、360 cases non-TB participants with lung disease and suspected TB patients who all meet the standard are divided into different groups through a randomized and blind method. Every subject inject intradermally ESAT6-CFP10 and TB-PPD (tuberculin purified protein derivative) in different arms of the same person by blind method. Specific gama-interferon (γ-IFN) detection is needed before the injection.Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. At the same time, we observe all kind of adverse events.

Detailed description: Firstly, 720 cases TB (Tuberculosis) participants who meet the standard respectively are divided into different groups through a randomized and blind method.

1. ESAT6-CFP10(10ug/ml) in left arm
2. ESAT6-CFP10(10ug/ml) in right arm. Inject intradermally ESAT6-CFP10 and TB-PPD in different arms of the same participant. For each of participant, the person in this clinical research, the study uniform is that every subject injects firstly left arm, observe no obvious adverse reaction, then another drug inject in right arm. Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. At the same time, we observe the vital signs (breathing, heart rate, blood pressure and temperature), local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events.

Secondly, 360 cases non-TB participants with lung disease and suspected TB participants are divided into two different groups and the procedure are as the same as 720 cases TB.

Thirdly,suspected TB participants are put under TB (Tuberculosis patients) or non-TB participants with lung disease by diagnosis when out group.

Finally, we calculate the sensitivity (positive coincidence rate) by TB (Tuberculosis patients), the specificity (negative coincidence rate) by non-TB participants with lung disease, and verify the safety and effectiveness of ESAT6-CFP10(10ug/ml) for the clinical auxiliary diagnosis of tuberculosis.

Eligibility criteria: Inclusion Criteria of TB (tuberculosis:include pulmonary tuberculosis and extra pulmonary tuberculosis) subjects:

* judge the pulmonary tuberculosis patient according to Health industry standard of the People's Republic of China WS288-2008:Diagnostic Criteria for pulmonary tuberculosis;
* 18 to 65 years old ,no gender limited;
* Consent and signed informed consent forms (ICF);
* Comply with follow-up.

Inclusion Criteria of extra pulmonary tuberculosis subjects:

* Diagnosed extra pulmonary tuberculosis by epidemiology, imaging, clinical symptoms, pathological examination and so on;
* Lesions outside the lungs;
* be in unfinished reinforced phase by chemotherapy;

Exclusion Criteria of TB (tuberculosis) subjects:

* Accompanied by the following severe illness:advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect;
* Taking part in other clinical or within three months involved in any other clinical;
* Severe allergic constitution:allergic to two or more drugs;
* in pregnancy or lactation;
* in a mental illness;
* Any conditions affect the trial evaluation by investigator's judgement.

Inclusion Criteria of non-TB participants with lung disease:

* A clear lung disease but can exclude pulmonary tuberculosis by clinical symptoms, imaging, laboratory examination.
* 18 to 65 years old, no gender limited;
* Consent and signed informed consent forms (ICF);
* Comply with follow-up.

Exclusion Criteria of non-TB participants with lung disease:

* Accompanied by the following severe illness: advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect;
* Taking part in other clinical or within three months involved in any other clinical;
* Severe allergic constitution: allergic to two or more drugs;
* in pregnancy or lactation;
* in a mental illness;
* history of tuberculosis;
* Any conditions affect the trial evaluation by investigator's judgement.

Inclusion Criteria of suspected TB participants with lung disease:

* Cases who have pulmonary tuberculosis by clinical symptoms/signs:appear cough、cough with hemoptysis、pectoralgia、dyspnea、fever（low-grade fever at afternoon）,together with night sweats、weak、loss of appetite、weight loss,and so on,or other easily-confused respiratory system disease with TB;
* 18 to 65 years old, no gender limited;
* Consent and signed informed consent forms (ICF);
* Comply with follow-up.

Exclusion Criteria of suspected TB participants with lung disease:

* Accompanied by the following severe illness: advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect;
* Taking part in other clinical or within three months involved in any other clinical;
* Severe allergic constitution: allergic to two or more drugs;
* in pregnancy or lactation;
* in a mental illness;
* history of tuberculosis;
* Any conditions affect the trial evaluation by investigator's judgement.

Primary outcomes:
measure: Immune response of left arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients
timeFrame: within 72h after injection
measure: Immune response of right arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients
timeFrame: within 72h after injection
measure: Immune response of left arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in non-TB subjects with lung disease
timeFrame: within 72h after injection
measure: Immune response of right arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in non-TB subjects with lung disease
timeFrame: within 72h after injection
Secondary outcomes:
measure: Number of participants with Adverse Events
timeFrame: within 72h after injection two drug each participant
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Wuxi NO.5 People's Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Public Health clinical Center
state: Shanghai
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 Institute for Tuberculosis Control
name: Weihua Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Chest Hospital
name: Naihui Chu, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuxi No.5 People's Hospital
name: Qinfang Ou
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Chongqing Medical University
name: Youlun Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fuzhou Pulmonary Hospital of fujuan
name: Xiaohong Chen
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhenjiang Third People's Hospital
name: Hongqiu Pan
role: PRINCIPAL_INVESTIGATOR
affiliation: Anhui Provincial Hospital
name: Xiaodong Mei, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen Third People's Hospital
name: Qunyi Deng, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Ravn P, Munk ME, Andersen AB, Lundgren B, Lundgren JD, Nielsen LN, Kok-Jensen A, Andersen P, Weldingh K. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis. Clin Diagn Lab Immunol. 2005 Apr;12(4):491-6. doi: 10.1128/CDLI.12.4.491-496.2005.
citation: Brusasca PN, Colangeli R, Lyashchenko KP, Zhao X, Vogelstein M, Spencer JS, McMurray DN, Gennaro ML. Immunological characterization of antigens encoded by the RD1 region of the Mycobacterium tuberculosis genome. Scand J Immunol. 2001 Nov;54(5):448-52. doi: 10.1046/j.1365-3083.2001.00975.x.
citation: Weldingh K, Andersen P. ESAT-6/CFP10 skin test predicts disease in M. tuberculosis-infected guinea pigs. PLoS One. 2008 Apr 23;3(4):e1978. doi: 10.1371/journal.pone.0001978.
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