Clinical trial NCT03027154: Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen for Children
Official title: For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 Dose Certain Phase III Clinical Research in Children Under the Age of 18 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tuberculosis Diagnosis
Keywords: diagnostic test
children
diagnosis of tuberculosis
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Public Health Clinical Center
name: Beijing Children's Hospital
name: Wuhan Institute for Tuberculosis Control
name: Wuhan Union Hospital, China
First posted: 2017-01-23
Enrollment: 96
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: In this clinical research,48 cases TB (Tuberculosis patients) participants and 48 cases non-TB participants with lung disease 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 in order to assess the safety of drug.

Detailed description: In this clinical research,we make sure of the safety in the crowd 5-18 years old firstly,then carry out the crowd of under 5 years old(including 5).

Firstly, 24 cases TB (Tuberculosis) participants and 24 cases non-TB participants with lung disease who are all 5-18 years old and meet the standard respectively are divided into different groups through a randomized and blind method.

1. ESAT6-CFP10(10ug/ml) in left arm and TB-PPD in right arm
2. ESAT6-CFP10(10ug/ml) in right arm and TB-PPD in left 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, 24 cases TB (Tuberculosis) participants and 24 cases non-TB participants with lung disease who are all less than 5 years old are divided into two different groups and the procedure are as the same as 5-18 years old.

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 Chinese Medical Association branch of pediatrics breathing group: Tuberculosis Clinical Diagnostic Criteria and Treatment Programs for Child (trial) ;
* less than 18 years old ,no gender limited;
* Consent and signed informed consent forms (ICF) by the subject or the guardian;
* The subject or with the help of guardian(s) 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: cancer, acute/progressive liver disease or kidney disease,autoimmune disease，diabetes, primary immunodeficiency diseases, other chronic diseases;
* Taking part in other clinical or within three months involved in any other clinical;
* Severe allergic constitution or familial history of allergy: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 respiratory disease but can exclude pulmonary tuberculosis by clinical symptoms, imaging, laboratory examination.
* less than 18 years old ,no gender limited;
* Consent and signed informed consent forms (ICF) by the subject or the guardian;
* The subject or with the help of guardian(s) comply with follow-up.

Exclusion Criteria of non-TB participants with lung disease:

* Accompanied by the following severe illness: cancer, acute/progressive liver disease or kidney disease,autoimmune disease，diabetes, primary immunodeficiency diseases, other chronic diseases， ect;
* Taking part in other clinical or within three months involved in any other clinical;
* Severe allergic constitution or familial history of allergy: allergic to two or more drugs;
* in pregnancy or lactation;
* in a mental illness;
* active tuberculosis close contactor;
* Any conditions affect the trial evaluation by investigator's judgement.

Primary outcomes:
measure: The diameter of induration or redness at the injection sites measured transversely to the long axis of the forearm 24 hours、48 hours and 72 hours after application of the agents
timeFrame: From injections to 1-3 days after aplication
Secondary outcomes:
measure: Number of participants with Adverse Events
timeFrame: within 72h after injection two drug each participant
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Medical Treatment Center
state: Hubei
city: Beijing
country: China
facility: Beijing Children's Hospital
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
city: Wuhan
country: China
facility: Wuhan Institute for Tuberculosis Control
Study officials:
affiliation: Shanghai Public Health Clinical Center
name: Shuihua Lu, BBachelor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: 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.