Tuberculosis
Conditions
Keywords
diagnosis of Tuberculosis (TB), ESAT6, CFP10, Phase IIa Clinical Trial
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.
Detailed description
First, 56 healthy subjects are distributed into different dose groups according to the recombinant EC allergen dose from low to high.Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test，after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram （before the skin test,after skin test 144h ）are the main test items,Evaluate the safety of the recombinant EC allergy in the expansion of the healthy people , and provide the appropriate dose range for phase IIb clinical trials. Second，56 patients of TB are distributed different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test，after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature),skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram （before the skin test,after skin test 144h ）are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB,and provide the appropriate dose range for phase IIb clinical trials. Third，32 patients of TB are distributed into different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of placebo as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test，after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration), local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram （before the skin test,after skin test 144h ）are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB on safety.
Interventions
BIOLOGICAL1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative
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.
BIOLOGICAL5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative
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.
BIOLOGICAL10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative
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.
BIOLOGICAL20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative
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.
BIOLOGICAL1μg/ml ESAT6-CFP10 and placebo
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.
BIOLOGICAL5μg/ml ESAT6-CFP10 and placebo
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.
BIOLOGICAL10μg/ml ESAT6-CFP10 and placebo
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.
BIOLOGICAL20μg/ml ESAT6-CFP10 and placebo
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.
Sponsors
Shanghai Public Health Clinical Center
Tianjin Haihe Hospital
Air Force Military Medical University, China
Proswell Medical Corporation
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
of healthy subjects: 1. 18 to 65 years old 2. Consent and signed ICF(informed consent forms) 3. Comply with follow-up 4. No history or family history of TB(tuberculosis) 5. Without the internal and external of pulmonary tuberculosis ; no symptoms of respiratory tract and other body parts for TB 6. The examination such as X-ray chest radiograph, sputum bacteria confirmed non-tuberculosis (TB) 7. No uncontrolled kinds of acute or chronic disease or acute infectious diseases or skin disease or skin allergies due to a variety of causes 8. 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 9. Did not attend any other new drug clinical trials and not vaccinate prevention products and immunoglobulin for nearly 3 months 10. Normal axillary temperature(quiet condition ≤37.0 ℃) 11. No smoking, no alcohol and drinking caffeinated beverages during the study
Exclusion criteria
of Healthy volunteers: 1. 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 2. Have seizures, epilepsy, brain and nervous system symptoms or signs of history 3. 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 4. Has acute febrile diseases and infectious diseases 5. Participate in other new drug clinical trials 6. Participated in any other new drug clinical trials in 3 months 7. 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 8. Women who are in pregnancy or lactation 9. People with mental or physical disabilities 10. Researchers consider that any conditions may affect the trial evaluation Inclusion Criteria of TB (tuberculosis)subjects: 1. Diagnosis TB according to the health of the People's Republic of China industry standard WS 288-2008 tuberculosis diagnostic criteria 2. Aged 18 to 65 years old 3. Consent and signed ICF to participate in this study 4. Comply with the requirements of the clinical research plan for follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 96 hours after intradermal injection | 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. |
| Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 24 hours after intradermal injection | 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 . |
| Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 24 hours after intradermal injection | 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. |
| Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 48 hours after intradermal injection | 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. |
| Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 48 hours after intradermal injection | 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. |
| Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 72 hours after intradermal injection | 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 |
| Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 72 hours after intradermal injection | 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. |
| Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 96 hours after intradermal injection | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection | before injection and after signed ICF(informed consent forms) | The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants. |
| 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 investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug. The percentage of positive(positive number/total number\*100%) is the sensitivity of IFN-γ in TB Participants. |
| 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 investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants. |
| 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 | The investigator draw 5ml venous blood for detection of IFN-γ 72 hours after injection with drug.The percentage of positive(positivenumber/total number\*100%) is the sensitivity of IFN-γ in in TB participants. |
| the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 144 hours after injection | The investigator draw 5ml venous blood for detection of IFN-γ 144 hours after injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants. |
| the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 144 hours after injection | The investigator draw 5ml venous blood for detection of IFN-γ 144 hours before injection with drug.The percentage of positive(positive number/total number\*100%) is the sensitivity of IFN-γ in in TB participants. |
| the Number of Participants With Adverse Events | before injection to 144 hours (plus or minus 2 hours) after injection | evaluate specific time point of vital signs, skin test reaction, blood routine, urine routine, liver and kidney function, electrocardiogram and adverse events as the incidence of adverse events in the participants . Skin test reaction observation time: at the end of the skin test, skin test after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours; Vital signs evaluation time: 0 minutes before the subjects were intradermal injection, intradermal injection after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours, 144 hours. Blood routine, urine routine, liver and kidney function, electrocardiogram (ecg) evaluation time: skin test before and 144 h after injection; adverse events evaluation time: participants signed a written informed consent to finish all the follow-up. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1μg/ml ESAT6-CFP10 The healthy subjects and TB subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (TB-PPD) or the placebo of ESAT6-CFP10 only one time in the different time .Right arm inject ESAT6-CFP10 and left arm inject TB-PPD or the placebo .Two drugs must be use in the same subjects. Left arm intradermally inject with 0.1ml TB-PPD(50IU/ml) or the placebo by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermally inject with 0.1ml ESAT6-CFP10 or the placebo of ESAT6-CFP10 by a syringe(1ml). | 35 |
| 5μg/ml ESAT6-CFP10 The healthy subjects and TB subjects inject 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (TB-PPD) or the placebo of ESAT6-CFP10 only one time in the different time .Right arm inject ESAT6-CFP10 and left arm inject TB-PPD or the placebo .Two drugs must be use in the same subjects. Left arm intradermally inject with 0.1ml TB-PPD(50IU/ml) or the placebo by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermally inject with 0.1ml ESAT6-CFP10 or the placebo of ESAT6-CFP10 by a syringe(1ml). | 34 |
| 10μg/ml ESAT6-CFP10 The healthy subjects and TB subjects inject 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (TB-PPD) or the placebo of ESAT6-CFP10 only one time in the different time .Right arm inject ESAT6-CFP10 and left arm inject TB-PPD or the placebo .Two drugs must be use in the same subjects. Left arm intradermally inject with 0.1ml TB-PPD(50IU/ml) or the placebo by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermally inject with 0.1ml ESAT6-CFP10 or the placebo of ESAT6-CFP10 by a syringe(1ml). | 36 |
| 20μg/ml ESAT6-CFP10 The healthy subjects and TB subjects inject 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (TB-PPD) or the placebo of ESAT6-CFP10 only one time in the different time .Right arm inject ESAT6-CFP10 and left arm inject TB-PPD or the placebo .Two drugs must be use in the same subjects. Left arm intradermally inject with 0.1ml TB-PPD(50IU/ml) or the placebo by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermally inject with 0.1ml ESAT6-CFP10 or the placebo of ESAT6-CFP10 by a syringe(1ml). | 36 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 20μg/ml ESAT6-CFP10 | 1μg/ml ESAT6-CFP10 | 10μg/ml ESAT6-CFP10 | 5μg/ml ESAT6-CFP10 |
|---|---|---|---|---|---|
| Age, Continuous | 41.76 years STANDARD_DEVIATION 12.42 | 44.63 years STANDARD_DEVIATION 12.37 | 40.12 years STANDARD_DEVIATION 12.83 | 43.81 years STANDARD_DEVIATION 12.53 | 38.46 years STANDARD_DEVIATION 11.98 |
| height | 166.52 cm STANDARD_DEVIATION 7.67 | 165.47 cm STANDARD_DEVIATION 7.81 | 166.83 cm STANDARD_DEVIATION 7.06 | 167.44 cm STANDARD_DEVIATION 8.23 | 166.32 cm STANDARD_DEVIATION 7.59 |
| Sex: Female, Male Female | 70 Participants | 17 Participants | 17 Participants | 16 Participants | 20 Participants |
| Sex: Female, Male Male | 71 Participants | 19 Participants | 18 Participants | 20 Participants | 14 Participants |
| weight | 60.78 kg STANDARD_DEVIATION 10.12 | 59.42 kg STANDARD_DEVIATION 11.56 | 62.20 kg STANDARD_DEVIATION 9.7 | 59.33 kg STANDARD_DEVIATION 9.4 | 62.15 kg STANDARD_DEVIATION 9.83 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 14 | 6 / 14 | 1 / 14 | 1 / 14 | 4 / 14 | 4 / 14 | 2 / 14 | 3 / 14 | 0 / 8 | 3 / 8 | 4 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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 .
Time frame: 24 hours after intradermal injection
Population: The percentage of negative(negative number/total number\*100%) is the specificity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 5μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 10μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 14 participants |
| 20μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Primary
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.
Time frame: 48 hours after intradermal injection
Population: The percentage of negative(negative number/total number\*100%) is the specificity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 5μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 10μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 20μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Primary
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
Time frame: 72 hours after intradermal injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 5μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 10μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 20μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Primary
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.
Time frame: 96 hours after intradermal injection
Population: The percentage of negative(negative number/total number\*100%) is the specificity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 5μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 10μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 20μg/ml ESAT6-CFP10 | Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Primary
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.
Time frame: 24 hours after intradermal injection
Population: The percentage of positive(positive number/total number\*100%) is the sensitivity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 15 participants |
| 5μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
| 10μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 20μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
Primary
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.
Time frame: 48 hours after intradermal injection
Population: The percentage of positive(positive number/total number\*100%) is the sensitivity of ESAT6-CFP10.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 15 participants |
| 5μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 10μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 20μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | 16 participants |
Primary
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.
Time frame: 72 hours after intradermal injection
Population: The percentage of positive(positive number/total number\*100%) is the sensitivity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 15 participants |
| 5μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 10μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 20μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 16 participants |
Primary
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.
Time frame: 96 hours after intradermal injection
Population: The percentage of positive(positive number/total number\*100%) is the sensitivity of ESAT6-CFP10 .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 14 participants |
| 5μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 10μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 20μg/ml ESAT6-CFP10 | Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | 15 participants |
Secondary
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 144 hours after injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants.
Time frame: 144 hours after injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 12 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 11 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 12 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Secondary
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants.
Time frame: 72 hours after injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 12 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 13 participants |
Secondary
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number\*100%) is the specificity of IFN-γ in healthy participants.
Time frame: before injection and after signed ICF(informed consent forms)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection | 12 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection | 13 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection | 13 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection | 13 participants |
Secondary
the Number of Participants With Adverse Events
evaluate specific time point of vital signs, skin test reaction, blood routine, urine routine, liver and kidney function, electrocardiogram and adverse events as the incidence of adverse events in the participants . Skin test reaction observation time: at the end of the skin test, skin test after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours; Vital signs evaluation time: 0 minutes before the subjects were intradermal injection, intradermal injection after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours, 144 hours. Blood routine, urine routine, liver and kidney function, electrocardiogram (ecg) evaluation time: skin test before and 144 h after injection; adverse events evaluation time: participants signed a written informed consent to finish all the follow-up.
Time frame: before injection to 144 hours (plus or minus 2 hours) after injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants With Adverse Events | 16 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants With Adverse Events | 19 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants With Adverse Events | 19 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants With Adverse Events | 14 participants |
Secondary
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 144 hours before injection with drug.The percentage of positive(positive number/total number\*100%) is the sensitivity of IFN-γ in in TB participants.
Time frame: 144 hours after injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 17 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 15 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
Secondary
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 72 hours after injection with drug.The percentage of positive(positivenumber/total number\*100%) is the sensitivity of IFN-γ in in TB participants.
Time frame: 72 hours after injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 18 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 18 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | 19 participants |
Secondary
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug. The percentage of positive(positive number/total number\*100%) is the sensitivity of IFN-γ in TB Participants.
Time frame: 4 hours before injection and after signed ICF(informed consent forms)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection | 18 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection | 17 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection | 18 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection | 19 participants |