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Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65 (IIb-healthy)

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

5μg/ml ESAT6-CFP10

10μg/ml ESAT6-CFP10

BCG

placebo

About this trial

This is an interventional diagnostic trial for Tuberculosis focused on measuring ESAT6, CFP10, skin test, diagnostic test

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria of study population Ⅰ:
1. 18 to 65 years old;
2. Consent and signed informed consent forms(ICF);
3. Comply with follow-up;
4. No history of tuberculosis;
5. Physical condition : No obvious heart, liver, kidney, gastrointestinal tract, nervous system, mental disorder and metabolic abnormalities and other medical history from signed informed consent to the injection within four weeks prior to delivery ;by the comprehensive physical examination showed electrocardiogram, blood pressure, heart rate, breathing and laboratory tests, including blood, urine routine, liver, kidney and other various biochemical test all without exception or slightly unusual but does not affect our research;
6. Normal axillary temperature(quiet condition ≤37.0 ℃).
Inclusion Criteria of study population Ⅱ:
1. healthy people conforming to the study population Ⅰ criteria ;
2. the result of three detection methods( ESAT6-CFP10 (5 μg/ml or 10 μg/ml)、 TB - PPD and specific gamma - IFN ) are all the negative ;
3. Comply with two criteria the above (1) (2) , HIV negative, X-ray chest radiograph no abnormalities.

Exclusion Criteria of study population Ⅰand study population Ⅱ:

Has the following serious disease, such as advanced cancer, diabetes, chronic obstructive pulmonary disease (copd) in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc;
Have epilepsy, brain and nervous system symptoms or signs of history or have risk tendency of epilepsy, brain and other nervous system disease and not easy to control;
Has known or suspected (or risk possible) immune damaged or abnormal functional , accept glucocorticoid and immunosuppressants or immunopotentiator treatment, outside the gastrointestinal tract protein or blood products or plasma extraction in 3 months, immunodeficiency virus infection or related diseases or long-term use of antibiotics;
Has acute febrile diseases and infectious diseases;
taking part in any other new drug clinical trials or participated in any other new drug clinical trials within 3 months before this trials;
allergy to drugs 、alcohol 、 vaccine、drugs using in this experiment and allergic or scar constitution;
In pregnancy or lactation;
With mental or physical disabilities;
Researchers consider that any conditions may affect the trial evaluation.

Sites / Locations

Jurong Province Centers for Disease Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

5μg/ml ESAT6-CFP10 after BCG immunization

10μg/ml ESAT6-CFP10 after BCG immunization

5μg/ml ESAT6-CFP10 after placebo immunization

10μg/ml ESAT6-CFP10 after placebo immunization

Arm Description

A within group paired comparison of 5μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 5μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after BCG immunization, according to a randomisation scheme .

A within group paired comparison of 10μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 10μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after BCG immunization, according to a randomisation scheme .

A within group paired comparison of 5μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 5μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after placebo controlled immunization, according to a randomisation scheme .

A within group paired comparison of 10μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 10μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after placebo controlled immunization, according to a randomisation scheme.

Outcomes

Primary Outcome Measures

immune response of ESAT6-CFP10 from the size of induration or redness in all population

We measure the size 24h,48h,72h after administered intradermally ESAT6-CFP10

immune response of TB-PPD from the size of induration or redness in all population

We measure the size 24h,48h,72h after administered intradermally TB-PPD

the results of specificity γ-IFN test in all subjects

Secondary Outcome Measures

the Number of Participants With Adverse Events

ESAT6-CFP10 cosistency with TB-PPD in all subjects

ESAT6-CFP10 cosistency with γ-IFN in all subjects

TB-PPD cosistency with γ-IFN in all subjects

Full Information

NCT ID

NCT02389322

First Posted

March 5, 2015

Last Updated

March 15, 2017

Sponsor

Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

Collaborators

Air Force Military Medical University, China, Proswell Medical Corporation, Jiangsu Province Centers for Disease Control and Prevention, Jurong Province Centers for Disease Control and Prevention

1. Study Identification

Unique Protocol Identification Number

NCT02389322

Brief Title

Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65

Acronym

IIb-healthy

Official Title

Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65,Adopting Randomized Blinded and Parallel Controlled Method

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

March 2015 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

Collaborators

Air Force Military Medical University, China, Proswell Medical Corporation, Jiangsu Province Centers for Disease Control and Prevention, Jurong Province Centers for Disease Control and Prevention

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The investigators select 500 subjects who meet the standard and are considered as study population I. Do specific gamma-interferon detection before the skin test， then inject intradermally with two dosage ESAT6-CFP10 and Tuberculin purified protein derivative (TB-PPD) at different arm of the same subject and get 192 participants whose three kinds of detection result are all negative and are considered as study population II.Then,they are immune to the Bacillus Calmette-Guerin (BCG) vaccine or the placebo of the BCG. Do specific gamma-interferon detection before the skin test， then inject intradermally with two dosage ESAT6-CFP10 and TB-PPD at different arm of the same subject 12 weeks after immunity.Negative rate of ESAT6-CFP10 after vaccination BCG as the main index , evaluate the specificity of different doses of ESAT6-CFP10, and conform the optimal dose of ESAT6-CFP10.

Detailed Description

1.the correlation of three detection methods for study population I 500 study population I are randomly divided into two different dose group on average, according to ESAT6-CFP10 dose(5μg/ml or 10μg/ml). Do specific gamma-interferon(γ-IFN) detection before the skin test，then inject intradermally with 5μg/ml ESAT6-CFP10 or 10μg/ml ESAT6-CFP10 and TB-PPD at different arm of the same subject.Evaluate respectively the positive rate of three detection methods 、the correlation of three detection methods and the security of study population I after application for ESAT6-CFP10 . 2.screen study population II Choose those participants, whose result of three detection (ESAT6-CFP10、TB-PPD andγ-IFN ) all negative, HIV negative and chest X-ray no abnormalities, into study population II. 3.study population II vaccinate BCG or placebo Study population II ,according to the same proportion ,are randomly divided into four group in double blinded state,: 5μg/ml ESAT6-CFP10 after BCG immunization, 10μg/ml ESAT6-CFP10 after BCG immunization, 5μg/ml ESAT6-CFP10 after placebo-controlled immunization , 10μg/ml ESAT6-CFP10 after placebo-controlled immunization.They vaccinate BCG or the placebo of BCG. 4.Inject ESAT6-CFP10 12 weeks after inoculation in study population II The investigators draw blood and operate specific gamma-interferon(γ-IFN) detection before the skin test，then inject intradermally with 5μg/ml ESAT6-CFP10 or 10μg/ml ESAT6-CFP10 (in double blinded state) and TB-PPD at different arm of the same subject ,according to the above grouping scheme. Calculate the negative coincidence rate and the correlation of three detection methods, and observe the safety of ESAT6-CFP10 in study population II at the same time.Evaluate the specificity of different doses of ESAT6-CFP10, negative rate of ESAT6-CFP10 after vaccination BCG as the main index. And finally conform the optimal dose of ESAT6-CFP10.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

ESAT6, CFP10, skin test, diagnostic test

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1044 (Actual)

8. Arms, Groups, and Interventions

Arm Title

5μg/ml ESAT6-CFP10 after BCG immunization

Arm Type

Experimental

Arm Description

Arm Title

10μg/ml ESAT6-CFP10 after BCG immunization

Arm Type

Experimental

Arm Description

Arm Title

5μg/ml ESAT6-CFP10 after placebo immunization

Arm Type

Placebo Comparator

Arm Description

A within group paired comparison of 5μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 5μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after placebo controlled immunization, according to a randomisation scheme .

Arm Title

10μg/ml ESAT6-CFP10 after placebo immunization

Arm Type

Placebo Comparator

Arm Description

A within group paired comparison of 10μg/ mL ESAT6-CFP10 and TB-PPD in 48 person of study population II. The 10μg/ mL ESAT6-CFP10 and TB-PPD agents are given concomitantly to each volunteer in the right and left forearms 12 weeks after placebo controlled immunization, according to a randomisation scheme.

Intervention Type

Biological

Intervention Name(s)

5μg/ml ESAT6-CFP10

Other Intervention Name(s)

5μg/mlEC

Intervention Description

The participants are injection intradermally with 0.1 ml 5μg/ml ESAT6-CFP10 12 weeks after BCG immunization or placebo immunization.This biological diagnostic reagents is injection agent .Every subject apply for the 5μg/mlRecombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 only one time after choosing into study population II .

Intervention Type

Biological

Intervention Name(s)

10μg/ml ESAT6-CFP10

Other Intervention Name(s)

10μg/ml EC

Intervention Description

The participants are injection intradermally with 0.1 ml 10μg/ml ESAT6-CFP10 12 weeks after BCG immunization or placebo immunization.This biological diagnostic reagents is injection agent .Every subject apply for the 10μg/mlRecombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 only one time after choosing into study population II .

Intervention Type

Biological

Intervention Name(s)

BCG

Other Intervention Name(s)

Bacillus Calmette-Guerin

Intervention Description

The participants are injected intradermally with 0.1 ml BCG.This BCG is Freeze-dried agent and with five people dose of each bottle,so each bottle of BCG must dissolve by 0.5ml special diluent before administration.Every subject apply for the BCG vaccine only one time after choosing into study population II .

Intervention Type

Biological

Intervention Name(s)

placebo

Intervention Description

The participants are injected intradermally with 0.1 ml placebo of Bacillus Calmette-Guerin.This placebo is Freeze-dried agent and with five people dose of each bottle ,so each bottle must dissolve by 0.5ml special diluent before administration.Every subject apply for the BCG vaccine only one time after choosing into study population II .

Primary Outcome Measure Information:

Title

immune response of ESAT6-CFP10 from the size of induration or redness in all population

Description

We measure the size 24h,48h,72h after administered intradermally ESAT6-CFP10

Time Frame

within 72 Hours After Intradermal Injection With ESAT6-CFP10

Title

immune response of TB-PPD from the size of induration or redness in all population

Description

We measure the size 24h,48h,72h after administered intradermally TB-PPD

Time Frame

within 72 Hours After Intradermal Injection With TB-PPD

Title

the results of specificity γ-IFN test in all subjects

Time Frame

before administered intradermally

Secondary Outcome Measure Information:

Title

the Number of Participants With Adverse Events

Time Frame

within 72 hours after injection

Title

ESAT6-CFP10 cosistency with TB-PPD in all subjects

Time Frame

within 72 hours after injection

Title

ESAT6-CFP10 cosistency with γ-IFN in all subjects

Time Frame

within 72 hours after injection

Title

TB-PPD cosistency with γ-IFN in all subjects

Time Frame

within 72 hours after injection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria of study population Ⅰ: 18 to 65 years old; Consent and signed informed consent forms(ICF); Comply with follow-up; No history of tuberculosis; Physical condition : No obvious heart, liver, kidney, gastrointestinal tract, nervous system, mental disorder and metabolic abnormalities and other medical history from signed informed consent to the injection within four weeks prior to delivery ;by the comprehensive physical examination showed electrocardiogram, blood pressure, heart rate, breathing and laboratory tests, including blood, urine routine, liver, kidney and other various biochemical test all without exception or slightly unusual but does not affect our research; Normal axillary temperature(quiet condition ≤37.0 ℃). Inclusion Criteria of study population Ⅱ: healthy people conforming to the study population Ⅰ criteria ; the result of three detection methods( ESAT6-CFP10 (5 μg/ml or 10 μg/ml)、 TB - PPD and specific gamma - IFN ) are all the negative ; Comply with two criteria the above (1) (2) , HIV negative, X-ray chest radiograph no abnormalities. Exclusion Criteria of study population Ⅰand study population Ⅱ: Has the following serious disease, such as advanced cancer, diabetes, chronic obstructive pulmonary disease (copd) in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc; Have epilepsy, brain and nervous system symptoms or signs of history or have risk tendency of epilepsy, brain and other nervous system disease and not easy to control; Has known or suspected (or risk possible) immune damaged or abnormal functional , accept glucocorticoid and immunosuppressants or immunopotentiator treatment, outside the gastrointestinal tract protein or blood products or plasma extraction in 3 months, immunodeficiency virus infection or related diseases or long-term use of antibiotics; Has acute febrile diseases and infectious diseases; taking part in any other new drug clinical trials or participated in any other new drug clinical trials within 3 months before this trials; allergy to drugs 、alcohol 、 vaccine、drugs using in this experiment and allergic or scar constitution; In pregnancy or lactation; With mental or physical disabilities; Researchers consider that any conditions may affect the trial evaluation.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wei Lu, Master

Organizational Affiliation

Jingsu Province Centers for Disease Control and Prevention

Official's Role

Principal Investigator

Facility Information:

Facility Name

Jurong Province Centers for Disease Control and Prevention

City

Jurong

State/Province

Jiangsu

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

10702486

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.

Results Reference

background

PubMed Identifier

15817755

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.

Results Reference

background

PubMed Identifier

11696195

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.

Results Reference

background

PubMed Identifier

18431468

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.

Results Reference

background

PubMed Identifier

17005738

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.

Results Reference

background

PubMed Identifier

34021314

Citation

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.

Results Reference

derived

Links:

URL

https://wbca.cde.org.cn/wbca/clinmain.do?method=edit&ckmIdCode=8BE5738082A97A9E5471F80B4F814FCF

Description

Center for drug evaluation,China Food and Drug Administration(CFDA) ,China

Learn more about this trial

Phase IIb Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 on Healthy People Aged 18-65

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