Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

Study Overview
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Brief Summary
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In the tests, small sample of clinical study about Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 ( Recombination EC Allergen） healthy adults was carried out. 24 healthy adults were included as study objects, they were randomly divided into four groups of different Recombinant Allergen EC dose (1, 5, 10μg/mL, maximum tolerated dose 20μg/mL, 6 person/dose) for single arm intradermal injection. The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) diameter of injection sites,local reaction ( rash, pain, itching, and skin and mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection . Preliminary evaluation of safety and tolerability of Recombinant Allergen EC applied in humans, which can provide a safe dosage range for phase II clinical study.

Detailed Description
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This clinical study adopts an open, randomized study methods to carry out Recombinant EC Allergen on small sample of healthy adults. 24 healthy adults were included as study objects, they were randomly divided into four groups of different Recombinant EC Allergen dose (1, 5, 10μg/mL, maximum tolerated dose 20μg/mL, 6 person/dose) for single arm intradermal injection, and set up two people as replacement for each group (one male and one female). Intradermal injection into one third site of healthy subjects' left or right forearm palmaris with 0.1ml Recombinant EC Allergen for only one time. The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) diameter of injection sites,local reaction ( rash, pain, itching, and skin and mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection . In phaseⅠclinical study, each person can accept only one dose, After injection of the same dose of a volunteer group, be sure the next injection of a volunteer at 40 minutes interval. Different dose groups: the next dose test should be carried on in the case of no serious adverse events appear in 7days after the last one volunteer's injection in a former lower dose group. Statistical analysis is performed using SAS9.3 software, and all analytic process is routinization.

Official Title
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Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

Conditions
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Healthy

Intervention / Treatment
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* Biological: ESAT6-CFP10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged from 18 to 40 years old, age difference is not more than 10 years old within the same batch of healthy volunteers, the male to female ratio of cases is 1:1. Body mass index should be in the range of 20 to 27 Body Mass Index BMI: weight (Kg)/ height (M2); Agreed to participate in the test and sign the informed consent; Subjects should comply with the requirements of the clinical trial protocol and be followed; Subjects have no history of TB (Tuberculosis)or family history of tuberculosis; People have no pulmonary tuberculosis or extrapulmonary tuberculosis,respiratory symptom or systemic symptoms; People have no tuberculosis focus after examination by X-ray chest radiograph and sputum bacilli; Subjects have no acute or chronic disease, acute infectious diseases, dermatoses or skin allergy caused by various reasons; Physical condition: have no history of heart, liver, kidney, gastrointestinal tract, nervous system, or metabolic disturbance, etc. ECG, blood pressure, heart rate, respiratory status and lab test indexes including blood, urine, liver and kidney function, etc are all normal within 4 weeks before screening; No close contacts of tuberculosis; Subjects have not participated in other clinical drug trials or inoculated against other prophylactic and immune globulin in the nearly 3 months; Temperature is normal; Stop smoking, drinking and drinking contains caffeinated. Exclusion Criteria: Health people have close contacts of TB (Tuberculosis)patients, especially excreter in 3 weeks before selection; Suffering from any other serious disease, e.g. during cancer treatment, autoimmune disease, progressive atherosclerosis, diabetes accompanied with complications, chronic obstructive pulmonary disease (COPD) needing oxygen therapy, acute or progressive liver or kidney disease, congestive heart failure, etc.; People have history of allergy, convulsions, epilepsy, cerebropathy, neurological symptoms and signs; Patients who have impaired or abnormal immune function, e.g. patients treated with immunosuppressor or immunopotentiator, received immunoglobulin preparation or blood products or plasma extraction outside the gastrointestinal tract in 3 months, human immunodeficiency virus or related diseases; Acute febrile illness and infection; Taking part in other clinic trials; Subjects have participated in any other clinical drug trials in 3 months before our clinical tests; Allergic constitution, e.g. patients have allergic history to two or more kinds of drugs or food, or drug components; Substance abuse and alcoholics ; Pregnant or breast feeding women; Mental or physical disability; Informed leavers; Any other cases that may influence the test evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1μg/ml ESAT6-CFP10<br>The 1μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme. | Biological: ESAT6-CFP10<br>* 32 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml ESAT6-CFP10、5μg/ml ESAT6-CFP10、10μg/ml ESAT6-CFP10、20μg/ml ESAT6-CFP10.Each dose group have six healthy subjects(three male and three female) , at the same time set up two people for substitute (one male and one female) . ESAT6-CFP10 administered intradermally by the mantoux injection technique. Each receives only one dosage in right or left arm .<br>* Other names: EC;|
| Experimental: 5μg/ml ESAT6-CFP10<br>The 5μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme. | Biological: ESAT6-CFP10<br>* 32 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml ESAT6-CFP10、5μg/ml ESAT6-CFP10、10μg/ml ESAT6-CFP10、20μg/ml ESAT6-CFP10.Each dose group have six healthy subjects(three male and three female) , at the same time set up two people for substitute (one male and one female) . ESAT6-CFP10 administered intradermally by the mantoux injection technique. Each receives only one dosage in right or left arm .<br>* Other names: EC;|
| Experimental: 10μg/ml ESAT6-CFP10<br>The 10μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme. | Biological: ESAT6-CFP10<br>* 32 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml ESAT6-CFP10、5μg/ml ESAT6-CFP10、10μg/ml ESAT6-CFP10、20μg/ml ESAT6-CFP10.Each dose group have six healthy subjects(three male and three female) , at the same time set up two people for substitute (one male and one female) . ESAT6-CFP10 administered intradermally by the mantoux injection technique. Each receives only one dosage in right or left arm .<br>* Other names: EC;|
| Experimental: 20μg/ml ESAT6-CFP10<br>The 20μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme. | Biological: ESAT6-CFP10<br>* 32 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml ESAT6-CFP10、5μg/ml ESAT6-CFP10、10μg/ml ESAT6-CFP10、20μg/ml ESAT6-CFP10.Each dose group have six healthy subjects(three male and three female) , at the same time set up two people for substitute (one male and one female) . ESAT6-CFP10 administered intradermally by the mantoux injection technique. Each receives only one dosage in right or left arm .<br>* Other names: EC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) of injection sites,local reaction ( rash, pain, itching, and skin mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection . | within 7 days after the injections | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | We check the immune response( induration and/or redness) at 2h after application of ESAT6-CFP10 with vernier caliper. Using the standardized vernier caliper, measured transverse diameter and the longitudinal diameter of induration and/or redness in skin test parts if any participants appear induration and/or redness after application of ESAT6-CFP10. | within 2h after application of ESAT6-CFP10 | 
| the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | We check the immune response( induration and/or redness) at 24h after application of ESAT6-CFP10 with vernier caliper. Using the standardized vernier caliper, measured transverse diameter and the longitudinal diameter of induration and/or redness in skin test parts if any participants appear induration and/or redness after application of ESAT6-CFP10. | 24h after application of ESAT6-CFP10 | 
| the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | We check the immune response( induration and/or redness) at 48h after application of ESAT6-CFP10 with vernier caliper. Using the standardized vernier caliper, measured transverse diameter and the longitudinal diameter of induration and/or redness in skin test parts if any participants appear induration and/or redness after application of ESAT6-CFP10. | 48h after application of ESAT6-CFP10 | 
| the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | We check the immune response( induration and/or redness) at 72h after application of ESAT6-CFP10 with vernier caliper. Using the standardized vernier caliper, measured transverse diameter and the longitudinal diameter of induration and/or redness in skin test parts if any participants appear induration and/or redness after application of ESAT6-CFP10. | 72h after application of ESAT6-CFP10 | 
| the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | We check the immune response( induration and/or redness) at 96h after application of ESAT6-CFP10 with vernier caliper. Using the standardized vernier caliper, measured transverse diameter and the longitudinal diameter of induration and/or redness in skin test parts if any participants appear induration and/or redness after application of ESAT6-CFP10. | 96h after application of ESAT6-CFP10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, ESAT6, CFP10, skin test, diagnostic test