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

Phase 2

Completed

Conditions: Tuberculosis

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

Registration Number: NCT02329730

Lead Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 144

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
the healthy subjects	10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the first part of tuberculosis subjects	20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the second part of tuberculosis subjects	1μg/ml ESAT6-CFP10 and placebo	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.
the second part of tuberculosis subjects	10μg/ml ESAT6-CFP10 and placebo	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.
the healthy subjects	1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the first part of tuberculosis subjects	5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the healthy subjects	5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the first part of tuberculosis subjects	1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the healthy subjects	20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the first part of tuberculosis subjects	10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative	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.
the second part of tuberculosis subjects	5μg/ml ESAT6-CFP10 and placebo	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.
the second part of tuberculosis subjects	20μg/ml ESAT6-CFP10 and placebo	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.

Primary Outcome Measures

Name	Time	Method
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 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 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 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 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 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 Outcome Measures

Name	Time	Method
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 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 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.
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 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.