Phase IIa Clinical Study of Recombinant Mycobacterium Tuberculosis Antigen ESAT6-CFP10
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 144
- 主要终点
- Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •of healthy subjects:
- •18 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
排除标准
- •of Healthy volunteers:
- •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
- •Inclusion Criteria of TB (tuberculosis)subjects:
- •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
- •Exclusion Criteria of TB volunteers:
- •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
- •Have seizures, epilepsy, brain and nervous system symptoms or signs of history;
- •Have 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
- •People in the pyrogenic stage with febrile diseases or infectious diseases (non tuberculosis)
- •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.
研究组 & 干预措施
the healthy subjects
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.
干预措施: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the healthy subjects
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.
干预措施: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the healthy subjects
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.
干预措施: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the healthy subjects
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.
干预措施: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the first part of tuberculosis subjects
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.
干预措施: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the first part of tuberculosis subjects
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.
干预措施: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the first part of tuberculosis subjects
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.
干预措施: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the first part of tuberculosis subjects
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.
干预措施: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative (Biological)
the second part of tuberculosis subjects
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.
干预措施: 1μg/ml ESAT6-CFP10 and placebo (Biological)
the second part of tuberculosis subjects
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.
干预措施: 5μg/ml ESAT6-CFP10 and placebo (Biological)
the second part of tuberculosis subjects
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.
干预措施: 10μg/ml ESAT6-CFP10 and placebo (Biological)
the second part of tuberculosis subjects
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.
干预措施: 20μg/ml ESAT6-CFP10 and placebo (Biological)
结局指标
主要结局
Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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 48 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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 Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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 48 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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 24 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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 72 Hours After Intradermal Injection With ESAT6-CFP10
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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 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)
- the Number of Participants With Adverse Events(before injection to 144 hours (plus or minus 2 hours) after injection)
- 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 144 Hours After Intradermal Injection With ESAT6-CFP10(144 hours after injection)
- 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)