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

NCT02329730 | Completed Phase 2 Results

• 1 other identifier: LTao-EC IIa
• Study Type: interventional
• Target: 144
• Locations: 0 countries
• Sites: N/A

Brief Summary

Choose healthy subjects and patients with TB, distribute them into different dose groups according to the recombinant EC allergen dose from low to high average. Conducting clinical trials of TB-PPD or placebo as controlled arms intradermal injection. Do specific interferon gamma detection before the skin test，after the test 72h±2h and 144h±2h. Evaluate the safety of the recombinant EC allergy , and provide the appropriate dose range for phase IIb clinical trials.

Conditions

Tuberculosis

Keywords

diagnosis of Tuberculosis (TB); ESAT6; CFP10; Phase IIa Clinical Trial

Outcome Measures

Primary Outcomes (8)

• Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 24 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. The percentage of negative(negative number/total number\*100%) is the specificity of ESAT6-CFP10 .

  24 hours after intradermal injection

• Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 24 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction.

  24 hours after intradermal injection

• Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 48 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction.

  48 hours after intradermal injection

• Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 48 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction.

  48 hours after intradermal injection

• Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 72 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. The percentage of negative(negative number/total number\*100%) is the specificity of ESAT6-CFP10

  72 hours after intradermal injection

• Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 72 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction.

  72 hours after intradermal injection

• Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 96 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction.

  96 hours after intradermal injection

• Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10

  The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 96 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction.

  96 hours after intradermal injection

Secondary Outcomes (7)

• the Number of Participants With Adverse Events

  before injection to 144 hours (plus or minus 2 hours) after injection

• the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection

  before injection and after signed ICF(informed consent forms)

• the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection

  4 hours before injection and after signed ICF(informed consent forms)

• the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10

  72 hours after injection

• the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10

  72 hours after injection

Study Arms (3)

the healthy subjects

EXPERIMENTAL

The healthy subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects.

Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative

the first part of tuberculosis subjects

EXPERIMENTAL

The first part kind of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects.

Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative

the second part of tuberculosis subjects

EXPERIMENTAL

The second part of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and placebo only one time , or 5μg/ml ESAT6-CFP10 and placebo only one time , or 10μg/ml ESAT6-CFP10 and placebo only one time , or 20μg/ml ESAT6-CFP10 and placebo only one time .Right arm inject ESAT6-CFP10 and left arm inject placebo. Two drugs must be use in the same subjects.

Biological: 1μg/ml ESAT6-CFP10 and placebo; Biological: 5μg/ml ESAT6-CFP10 and placebo; Biological: 10μg/ml ESAT6-CFP10 and placebo; Biological: 20μg/ml ESAT6-CFP10 and placebo

Interventions

1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative BIOLOGICAL

Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD

the first part of tuberculosis subjects; the healthy subjects

5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative BIOLOGICAL

Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10/TB-PPD

the first part of tuberculosis subjects; the healthy subjects

10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative BIOLOGICAL

Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD

the first part of tuberculosis subjects; the healthy subjects

20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative BIOLOGICAL

Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD

the first part of tuberculosis subjects; the healthy subjects

1μg/ml ESAT6-CFP10 and placebo BIOLOGICAL

Left arm intradermal injection of the placebo of 1μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

the second part of tuberculosis subjects

5μg/ml ESAT6-CFP10 and placebo BIOLOGICAL

Left arm intradermal injection of the placebo of 5μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

the second part of tuberculosis subjects

10μg/ml ESAT6-CFP10 and placebo BIOLOGICAL

Left arm intradermal injection of the placebo of 10μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

the second part of tuberculosis subjects

20μg/ml ESAT6-CFP10 and placebo BIOLOGICAL

Left arm intradermal injection of the placebo of 20μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

the second part of tuberculosis subjects

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 ICF(informed consent forms)
• Comply with follow-up
• No history or family history of TB(tuberculosis)
• Without the internal and external of pulmonary tuberculosis ; no symptoms of respiratory tract and other body parts for TB
• The examination such as X-ray chest radiograph, sputum bacteria confirmed non-tuberculosis (TB)
• No uncontrolled kinds of acute or chronic disease or acute infectious diseases or skin disease or skin allergies due to a variety of causes
• 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
• Did not attend any other new drug clinical trials and not vaccinate prevention products and immunoglobulin for nearly 3 months
• Normal axillary temperature(quiet condition ≤37.0 ℃)
• No smoking, no alcohol and drinking caffeinated beverages during the study

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 seizures, epilepsy, brain and nervous system symptoms or signs of history
• 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
• Has acute febrile diseases and infectious diseases
• Participate in other new drug clinical trials
• Participated in any other new drug clinical trials in 3 months
• Allergic people who have histories of allergy to two or more drugs/food allergy and physical scars, are allergic to alcohol or drugs known to the group of points
• Women who are in pregnancy or lactation
• People with mental or physical disabilities
• Researchers consider that any conditions may affect the trial evaluation
• Diagnosis TB according to the health of the People's Republic of China industry standard WS 288-2008 tuberculosis diagnostic criteria
• Aged 18 to 65 years old
• Consent and signed ICF to participate in this study
• Comply with the requirements of the clinical research plan for follow-up
• Have 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

Sponsors & Collaborators

• Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.: lead
• Shanghai Public Health Clinical Center: collaborator
• Tianjin Haihe Hospital: collaborator
• Air Force Military Medical University, China: collaborator
• Proswell Medical Corporation: collaborator

Related Publications (5)

• 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

Related Links

• Center for drug evaluation, CFDA ,China

MeSH Terms

Conditions

Tuberculosis

Interventions

Tuberculin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antigens, Bacterial; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors

Results Point of Contact

• Title: Shuihua Lu
• Organization: Shanghai Public Health Clinical Center

tubercle@gmail.com

021-37990333

Study Officials

• Shuihua Lu, Bachelor

  Shanghai Public Health Clinical Center

  PRINCIPAL INVESTIGATOR

• Qi Wu, Master

  Tianjin Haihe Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: January 1, 2015
• Study Start: February 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: August 1, 2014
• Last Updated: April 9, 2015
• Results First Posted: April 9, 2015

Record last verified: 2015-03