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

NCT02389322 | Completed Phase 2

• 1 other identifier: EC-IIb-healthy
• Study Type: interventional
• Target: 1,044
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis

Keywords

ESAT6; CFP10; skin test; diagnostic test

Outcome Measures

Primary Outcomes (3)

• 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

  within 72 Hours After Intradermal Injection With 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

  within 72 Hours After Intradermal Injection With TB-PPD

• the results of specificity γ-IFN test in all subjects

  before administered intradermally

Secondary Outcomes (4)

• the Number of Participants With Adverse Events

  within 72 hours after injection

• ESAT6-CFP10 cosistency with TB-PPD in all subjects

  within 72 hours after injection

• ESAT6-CFP10 cosistency with γ-IFN in all subjects

  within 72 hours after injection

• TB-PPD cosistency with γ-IFN in all subjects

  within 72 hours after injection

Study Arms (4)

5μg/ml ESAT6-CFP10 after BCG immunization

EXPERIMENTAL

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 .

Biological: 5μg/ml ESAT6-CFP10; Biological: BCG

10μg/ml ESAT6-CFP10 after BCG immunization

EXPERIMENTAL

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 .

Biological: 10μg/ml ESAT6-CFP10; Biological: BCG

5μg/ml ESAT6-CFP10 after placebo immunization

PLACEBO COMPARATOR

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 .

Biological: placebo

10μg/ml ESAT6-CFP10 after placebo immunization

PLACEBO COMPARATOR

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.

Biological: placebo

Interventions

5μg/ml ESAT6-CFP10 BIOLOGICAL

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 .

Also known as: 5μg/mlEC

5μg/ml ESAT6-CFP10 after BCG immunization

10μg/ml ESAT6-CFP10 BIOLOGICAL

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 .

Also known as: 10μg/ml EC

10μg/ml ESAT6-CFP10 after BCG immunization

BCG BIOLOGICAL

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 .

Also known as: Bacillus Calmette-Guerin

10μg/ml ESAT6-CFP10 after BCG immunization; 5μg/ml ESAT6-CFP10 after BCG immunization

placebo BIOLOGICAL

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 .

10μg/ml ESAT6-CFP10 after placebo immunization; 5μg/ml ESAT6-CFP10 after placebo immunization

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ℃).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.: lead
• Air Force Military Medical University, China: collaborator
• Proswell Medical Corporation: collaborator
• Jiangsu Province Centers for Disease Control and Prevention: collaborator
• Jurong Province Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Jurong Province Centers for Disease Control and Prevention

Jurong, Jiangsu, China

Location

Related Publications (6)

• 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.

  PMID: 10702486 BACKGROUND

• 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.

  PMID: 15817755 BACKGROUND

• 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.

  PMID: 11696195 BACKGROUND

• 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.

  PMID: 18431468 BACKGROUND

• 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.

  PMID: 17005738 BACKGROUND

• 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.

  PMID: 34021314 DERIVED

Related Links

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

MeSH Terms

Conditions

Tuberculosis

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Wei Lu, Master

  Jingsu Province Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: March 17, 2015
• Study Start: March 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 17, 2017

Record last verified: 2015-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)