Healthy
Conditions
Keywords
Safety, Tolerability, ESAT6, CFP10, skin test, diagnostic test
Brief summary
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
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.
Interventions
BIOLOGICALESAT6-CFP10
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 .
Sponsors
Shanghai Public Health Clinical Center
Air Force Military Medical University, China
Proswell Medical Corporation
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | within 7 days after the injections | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | within 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. |
| the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | 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. |
| the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | 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. |
| the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | 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. |
| the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | 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. |
Participant flow
Recruitment details
In September 4, 2013, the recruitment carried out in Shanghai Public Health Clinical Center.
Participants by arm
| Arm | Count |
|---|---|
| 1μg/ml ESAT6-CFP10 24 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、5μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、10μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、20μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10.Each dose group have six healthy subjects , at the same time set up two people for substitute (one male and one female) . | 6 |
| 5μg/ml ESAT6-CFP10 24 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、5μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、10μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、20μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10.Each dose group have six healthy subjects , at the same time set up two people for substitute (one male and one female) . | 6 |
| 10μg/ml ESAT6-CFP10 24 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、5μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、10μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、20μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10.Each dose group have six healthy subjects , at the same time set up two people for substitute (one male and one female) . | 6 |
| 20μg/ml ESAT6-CFP10 24 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、5μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、10μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10、20μg/ml Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10.Each dose group have six healthy subjects , at the same time set up two people for substitute (one male and one female) . | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | 1μg/ml ESAT6-CFP10 | 5μg/ml ESAT6-CFP10 | 10μg/ml ESAT6-CFP10 | 20μg/ml ESAT6-CFP10 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.00 years STANDARD_DEVIATION 3.93 | 25.63 years STANDARD_DEVIATION 4.13 | 30.07 years STANDARD_DEVIATION 4 | 27.68 years STANDARD_DEVIATION 3.79 | 27.10 years STANDARD_DEVIATION 3.96 |
| Body Mass Index | 22.32 kg/m^2 STANDARD_DEVIATION 2.03 | 23.07 kg/m^2 STANDARD_DEVIATION 2.05 | 22.05 kg/m^2 STANDARD_DEVIATION 1.13 | 22.88 kg/m^2 STANDARD_DEVIATION 2.11 | 22.58 kg/m^2 STANDARD_DEVIATION 1.83 |
| height | 169.17 cm STANDARD_DEVIATION 11.97 | 169.00 cm STANDARD_DEVIATION 9.67 | 163.00 cm STANDARD_DEVIATION 5.06 | 164.83 cm STANDARD_DEVIATION 11.11 | 166.50 cm STANDARD_DEVIATION 9.45 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 1 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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 .
Time frame: within 7 days after the injections
Population: ESAT6-CFP10 allergen similar to TB-PPD(Tuberculin purified protein derivative ), main ingredients are protein and can cause specific skin allergy in the injection site ( such as redness, swelling, induration, blisters), besides other local reactions, is still listed as adverse events .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | 3 cases |
| 5μg/ml ESAT6-CFP10 | the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | 1 cases |
| 10μg/ml ESAT6-CFP10 | the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | 0 cases |
| 20μg/ml ESAT6-CFP10 | the Cases of Adverse Events With Participant Injection of ESAT6-CFP10 | 0 cases |
Secondary
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.
Time frame: 24h after application of ESAT6-CFP10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | 0 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | 0 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | 0 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10 | 0 participants |
Secondary
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.
Time frame: within 2h after application of ESAT6-CFP10
Population: Induration and/or redness is our main immune response of ESAT6-CFP10.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | 0 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | 0 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | 0 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10 | 0 participants |
Secondary
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.
Time frame: 48h after application of ESAT6-CFP10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | 0 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | 0 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | 0 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10 | 0 participants |
Secondary
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.
Time frame: 72h after application of ESAT6-CFP10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | 0 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | 0 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | 0 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10 | 0 participants |
Secondary
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.
Time frame: 96h after application of ESAT6-CFP10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | 0 participants |
| 5μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | 0 participants |
| 10μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | 0 participants |
| 20μg/ml ESAT6-CFP10 | the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10 | 0 participants |