Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
March 21, 2017 updated by: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6 - CFP10 Dose of Certain Phase IIb Clinical Research
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.
Study Overview
Status
Completed
Conditions
Detailed Description
Firstly,96 TB(Tuberculosis ) subjects which meet the standard respectively are divided into different groups through a randomized, blind methods.
- ESAT6-CFP10 （5μg/ml）in left arm；
- ESAT6-CFP10 （5μg/ml）in right arm；
- ESAT6-CFP10 （10μg/ml）in left arm；
- 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 .
Study Type
Interventional
Enrollment (Actual)
192
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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 ) 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: TB subjects
96 TB subjects are divided into four groups average .24
TB subjects are injected 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 10μg/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 left arm and TB-PPD in right arm respectively.
Two drug must use at the same person and different 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.
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.
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.
|
|
Active Comparator: non-TB subjects with lung disease
96 non-TB subjects with lung disease are divided into four groups average .24
TB subjects are injected 5μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 5μg/ml ESAT6-CFP10 in right arm and TB-PPD in left arm,24 TB subjects are injected 10μg/ml ESAT6-CFP10 in left arm and TB-PPD in right arm,24 TB subjects are injected 10μg/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 left arm and TB-PPD in right arm respectively.
Two drug must use at the same person and different 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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
the diameter of induraton or redness within 72 hours after intradermal injection with ESAT6-CFP10 in TB patients
Time Frame: within 72h after injection
|
we measure the size 15min,24h,48h,72h after administered intradermally ESAT6-CFP10
|
within 72h after injection
|
|
the proportion of positive reaction within 72 hours after administered intradermally TB-PPD in TB patient
Time Frame: within 72h after injection
|
we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD
|
within 72h after injection
|
|
Immune response of of ESAT6-CFP10 from the size of induration OR redness in non-TB patients with lung diseases
Time Frame: within 72h after injection
|
we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD
|
within 72h after injection
|
|
The proportion of positive reaction after receiving specificity γ-IFN test in TB subjects and non-TB subjects with lung disease
Time Frame: before administered intradermally
|
before administered intradermally
|
|
|
the proportion of positive reaction within 72 hours after intradermal injection with TB-PPD in non-TB patients with lung diseases
Time Frame: within 72h after injection
|
we measure the size at 15min,24h,48h,72h after administered intradermally TB-PPD
|
within 72h after injection
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
the occurrence of adverse events within 72 hours after injection in TB subjects and non-TB subjects with lung disease
Time Frame: within 72h after injection two drugs
|
within 72h after injection two drugs
|
|
the consistency between ESAT6-CFP10 and TB-PPD in TB subjects and non-TB subjects with lung disease
Time Frame: within 72h after injection
|
within 72h after injection
|
|
the consistency between ESAT6-CFP10 and γ-IFN in TB subjects and non-TB subjects with lung disease
Time Frame: within 72h after injection
|
within 72h after injection
|
|
the consistency between TB-PPD and γ-IFN in TB subjects and non-TB subjects with lung disease
Time Frame: within 72h after injection
|
within 72h after injection
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Weihua Wang, Doctor, Wuhan Insititute for Tuberculosis Control
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2014
Primary Completion (Actual)
July 1, 2015
Study Completion (Actual)
July 1, 2015
Study Registration Dates
First Submitted
December 24, 2014
First Submitted That Met QC Criteria
January 8, 2015
First Posted (Estimate)
January 13, 2015
Study Record Updates
Last Update Posted (Actual)
March 23, 2017
Last Update Submitted That Met QC Criteria
March 21, 2017
Last Verified
September 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LTao-IIb-patient
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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