A Phase ⅠStudy of the Recombinant Mycobacterium Tuberculosis Vaccine Freeze-dried
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      There are four populations in Recombinant Mycobacterium tuberculosis Vaccine Freeze-dried
      (AEC/BC02) phase I clinical research. The clinical study adopt open research design.

      Population I have 25 subjects who received Tuberculin purified protein derivative(TB-PPD)
      skin test and specific gamma-interferon (γ-IFN)detection whose results are both negative
      ;Population II have 30 subjects who received Tuberculin purified protein derivative(TB-PPD)
      and ESAT6-CFP10 skin test in different arms , specific gamma-interferon (γ-IFN) detection
      whose results are all negative.We call polulation III as uninfected TB PPD positve
      population.This group screened 30 subjects whose ESAT6-CFP10 skin test and specific
      gamma-interferon (γ-IFN)detection results are both negative,but Tuberculin purified protein
      derivative(TB-PPD) skin test positive.50 subjects whose three kinds of detection results are
      all positive γ-IFN,TB-PPD and ESAT6-CFP10 ) are named as population IV.

      After filtrating, injecting of population I start firstly.After ensure the safety of the
      population I,the population II～polulation IV carry out in turn the implementation at the same
      time.
    

Detailed description: 
      Consider the safety of the inoculation,the trial is conducted in the following order:

      Population I start firstly, polulation II～population IV is sarted when population I is
      finished the entire immune and observation safety.Population II and population III should
      proceed simultaneously,and these two kinds of population finish injecting the first doses of
      placebo group after 4weeks,population IV start.

      All participants of the placebo group and adjuvant group complete the first needle
      intramuscular injection.5 subjects of Low-dose vaccine group are injected after being sure of
      the security of placebo and adjucant groups after 3 days. When these low-dose vaccine
      subjects is sure of safety in 2h,the rest of 5 subjects are injected.Each participant immune
      one type of placebo, adjuvant or vaccination every two weeks, totally six stitches. In the
      research, each subject receives only one dose of drug and cannot be subjected to experiments
      about dose escalation.

      The population Ⅰ subjects are received 6 needle times of placebo or low-dose adjuvant or
      low-dose vaccine by haunch deep intramuscular injection to provide security basis. The
      subjects should accept some physical examination during the clinical research. Vital signs
      (breathing, pulse, blood pressure, body temperature) of each volunteer before each needle
      injection and 30min; and local reaction of each volunteer at 30min after injection;routine
      blood, routine urine, liver and kidney function, and ECG before first-dose,
      third-dose,forth-dose and sixth-dose,7 days after the sixth needle injection; Female HCG is
      tested before each needle injection and 7days after the sixth dose injected; chest X-ray
      detection before the first injection and 7 days after the sixth needle injection. All
      subjects should assess the changes of immunological indexes before the first injection, the
      fourth time before injection and 7 days after the sixth needle injection. The specific
      injection orders are as follows:

      ①All the subjects of placebo group(5 cases) and low-dose adjuvant group(10 cases) will be
      injected on the same day, the adjuvant group subjects should be injected after all the
      placebo group completed and observed two hours safety;

      ② All the subjects of low-dose vaccine (10 cases) will be injected on the third day if the
      placebo group and adjuvant group subjects are observed safety.

      ③The clinical study of population Ⅱ and population Ⅲ will be carried out 3 days later if the
      low-dose vaccine group subjects of the population Ⅰ are observed safety; Each subject
      inoculates a dose of drug every two weeks, a total of six agents. In conclusion, the result
      of the Phase I Clinical Study of population I evaluate safety of different dose of
      Recombinant Mycobacterium tuberculosis Vaccine Freeze-dried(AEC/BCO2) in different
      population, but also provide a safe basis for the Phase I Clinical Study.

      The populationⅠsubjects are injected the first needle injection and observe safety after 3
      days and then conducted clinical research population Ⅱ and Ⅲ in Phase I Clinical. The study
      population Ⅱ/Ⅲ will be injected to a placebo or adjuvant or vaccination and collect any
      adverse events and serious adverse events to evaluate its safety during the period of
      clinical research.When the above two kinds of population are injected first doses of placebo
      after 4 weeks,the low-dose group of population IV proceed.High-dose group of population IV
      conduct trial after the low-dose group injected first dose of placebo later 1 week.

      The 30 subjects of study population Ⅱand 30 subjects of population III who meet the inclusion
      criteria and do not accord with standard of exclusion are divided into placebo
      group,high-dose adjuvant group and high-dose vaccine group, each group has 10
      participants.The 50 subjects of population IV are invidided into low-dose group and high-dose
      group,each group of 25 subjects.The Low-dose group consiste of 5 placebo subjects,10 adjuvant
      subjects and 10 vaccine subjects.The high-dose grouping is same as low-dose group.Every
      subject must accept some physical examination during the clinical research,and all the items
      of physical examination are as same as population I. Specific injection orders are as
      follows:

      ①Population II and population III should proceed simultaneously,and these two kinds of
      population finish injecting the first doses of placebo group after 4weeks,population IV
      start;

      ②High-dose group of population IV conduct trial after the low-dose group injected first dose
      of placebo later 1 week;

      ③Every pupolation are injected placebo and adjuvant firstly;5 subjects of Low-dose vaccine
      group are injected after being sure of the security of placebo and adjucant groups after 3
      days. When these low-dose vaccine subjects is sure of safety in 2h,the rest of 5 subjects are
      injected.

      All subjects are vaccinated once every two weeks, a total of six times vaccination.
    

Intervention name(s): Placebo; Low dose adjuvant; High dose adjuvant; Low dose vaccine; High dose vaccine
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): The placebo drug contains 20mg mannitol and 10 millimole(mM) phosphate buffer(PB).population I～population IV are coxal muscle injection of placebo.; Population I and polulation IV are coxal muscle injection of low dose adjuvant.; Population II ,Population III and Population IV are coxal muscle injection of high dose adjuvant.; Population I and population IV are coxal muscle injection of low dose vaccine.; Population II,population III and population IV are coxal muscle injection of high dose vaccine .
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Safety; Tolerance