Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen

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

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm; Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1090
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Wuxi, Jiangsu, China
      • Wuxi No.5 People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Public Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TB subjects; 720 cases TB (Tuberculosis) subjects who meet the standard respectively are divided average into two groups through a randomized and blind method. 360 TB subjects are injected ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm. 360 TB subjects are injected ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm. 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.	Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm; All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm respectively. Two drug must use at the same participant and in different arms.; Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm; All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm respectively. Two drug must use at the same participant and in different arms.
EXPERIMENTAL: non-TB subjects with lung disease and suspected TB subjects; 360 cases non-TB subjects with lung disease and suspected TB subjects,who meet the standard respectively are divided average into different groups through a randomized and blind method. 180 non-TB subjects with lung disease are injected ESAT6-CFP10(10ug/ml) in left arm and TB-PPD in right arm. 180 non-TB subjects with lung disease are injected ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm. 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.	Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm; All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm respectively. Two drug must use at the same participant and in different arms.; Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm; All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm respectively. Two drug must use at the same participant and in different arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response of left arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients	We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally left arm (random injected ESAT6-CFP10 or PPD)	within 72h after injection
Immune response of right arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients	We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally right arm (random injected ESAT6-CFP10 or PPD)	within 72h after injection
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	We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally left arm (random injected ESAT6-CFP10 or PPD)	within 72h after injection
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	We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally right arm (random injected ESAT6-CFP10 or PPD)	within 72h after injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Adverse Events	within 72h after injection two drug each participant

Collaborators and Investigators

• Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
• Collaborators: Beijing Chest Hospital; Fuzhou Pulmonary Hospital of Fujian; Shanghai Public Health Clinical Center; Air Force Military Medical University, China; First Affiliated Hospital of Chongqing Medical University; Anhui Provincial Hospital; Shenzhen Third People's Hospital; Tianjin Haihe Hospital; Wuhan Institute for Tuberculosis Control; Proswell Medical Corporation; Wuxi Hospital for Infectious Diseases; Zhenjiang Third People's Hospital
• Investigators: Principal Investigator: Weihua Wang, Doctor, Wuhan Institute For Tuberculosis Control; Principal Investigator: Naihui Chu, Bachelor, Beijing Chest Hospital; Principal Investigator: Qinfang Ou, Wuxi No.5 People's Hospital; Principal Investigator: Youlun Li, Doctor, First Affiliated Hospital of Chongqing Medical University; Principal Investigator: Xiaohong Chen, Fuzhou Pulmonary Hospital of fujuan; Principal Investigator: Hongqiu Pan, Zhenjiang Third People's Hospital; Principal Investigator: Xiaodong Mei, Doctor, Anhui Provincial Hospital; Principal Investigator: Qunyi Deng, Doctor, Shenzhen Third People's Hospital

Publications and helpful links

General Publications

• van Pinxteren LA, Ravn P, Agger EM, Pollock J, Andersen P. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clin Diagn Lab Immunol. 2000 Mar;7(2):155-60. doi: 10.1128/CDLI.7.2.155-160.2000.
• 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.
• 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.
• 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.
• Aagaard C, Govaerts M, Meikle V, Vallecillo AJ, Gutierrez-Pabello JA, Suarez-Guemes F, McNair J, Cataldi A, Espitia C, Andersen P, Pollock JM. Optimizing antigen cocktails for detection of Mycobacterium bovis in herds with different prevalences of bovine tuberculosis: ESAT6-CFP10 mixture shows optimal sensitivity and specificity. J Clin Microbiol. 2006 Dec;44(12):4326-35. doi: 10.1128/JCM.01184-06. Epub 2006 Sep 27.

Helpful Links

• Center for drug evaluation, CFDA, China
• Chinese Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (ESTIMATE): December 7, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: diagnosis of tuberculosis; diagnostic test; skin test; ESAT6-CFP10
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: LTao-EC III-patient

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO