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

Tuberculosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02336542
• Other study ID #: LTao-IIb-patient
• Status: Completed
• Phase: Phase 2
• First received: December 24, 2014
• Last updated: March 21, 2017
• Start date: November 2014
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mycobacterium Infections
• Tuberculosis

Intervention

Biological:
• 5µg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm
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.
• 5µg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm
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.
• 10µg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm
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.
• 10µg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm
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.

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.	Fourth Military Medical University, Proswell Medical Corporation, Shanghai Public Health Clinical Center, Tianjin Haihe Hospital, Wuhan Institute for Tuberculosis Control

References & Publications (5)

Aagaard C, Govaerts M, Meikle V, Vallecillo AJ, Gutierrez-Pabello JA, Suarez-Güemes 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	The proportion of positive reaction after receiving specificity ?-IFN test in TB subjects and non-TB subjects with lung disease		before administered intradermally
Primary	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	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
Secondary	the consistency between ESAT6-CFP10 and TB-PPD in TB subjects and non-TB subjects with lung disease		within 72h after injection
Secondary	the consistency between ESAT6-CFP10 and ?-IFN in TB subjects and non-TB subjects with lung disease		within 72h after injection
Secondary	the consistency between TB-PPD and ?-IFN in TB subjects and non-TB subjects with lung disease		within 72h after injection

External Links

•   Center for drug evaluation, CFDA ,China