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Phase III Clinical Study of Efficacy and Safety of Vaccae™ to Prevent Tuberculosis

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Vaccae
placebo
Sponsored by
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring TB Infection, Lesion Degree, Bacteriology Indicators, Cavity, Humoral Immunity, Cellular Immunologic Response

Eligibility Criteria

15 Years - 65 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Aged from 15 to 65 years old, all genders.
  • Skin test of Tuberculin Pure Protein Derivative (TB-PPD) is strongly positive ( the average diameter of PPD skin test induration is greater than or equal to 15mm,and（or）local blisters, necrosis).
  • Agreed to participate in the test and sign the informed consent.
  • Subjects agreed to participate in the experiments and voluntarily signed the informed consent. (guardians of 15-17- year-old subjects should agree, meanwhile).
  • The subjects should comply with the requirements of the clinical trial protocol and be Followed.
  • Have not participated in any other clinical trial for nearly three months.
  • Women of childbearing age from 15 to 49 years should agree with urine pregnancy tests and take effective birth control measures in two years after the medication.
  • Axillary temperature is normal.

Exclusion Criteria:

The first injection drug exclusion criteria :

  • 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.
  • Known allergy to experiment drugs
  • People with history of specific diagnosis of TB, extrapulmonary tuberculosis or have been cured
  • 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
  • Oral corticosteroids
  • Patients who have been using oral corticosteroids for more than 1 week, or hormone medication in vitro for a long time
  • Acute febrile illness and infection
  • Pregnant or lactating women, or women who have birth plan in following 2 years
  • Any other cases that may influence the test evaluation

The second-sixth injection drug exclusion criteria :

  • Subjects whose compliance is poor, and can not take medicine on time or according to the amount
  • Patients who are using medicine and food that can influence the result
  • Pregnant subjects during the test
  • Patients who are reluctant to continue and require exit

Sites / Locations

  • Jin Chengjiang Center for Diseases Control and Prevention, Hechi, Guangxi
  • Liucheng County Diseases Control and Prevention, Liuzhou, Guangxi
  • Liuzhou Center for Diseases Control and Prevention, Liuzhou, Guangxi
  • Rongshui County Diseases Control and Prevention, Liuzhou, Guangxi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vaccae

Placebo

Arm Description

Experiment group:One vial of Vaccae diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well, once every 2 weeks, 6 times totally.

Placebo group:One vial of placebo diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well, once every 2 weeks, 6 times totally

Outcomes

Primary Outcome Measures

The whole TB incidence after injection of Vaccae
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease

Secondary Outcome Measures

Lesion degree (Bacteriology indicators, cavity) of patients
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease
Systemic and local reactions and adverse events
within 30 days after last dosing
The relation between skin test results and paroxysm of TB-PPD
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease

Full Information

First Posted
November 4, 2013
Last Updated
May 30, 2018
Sponsor
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Collaborators
Guangxi Center for Disease Control and Prevention, Liuzhou Center for Disease Control and Prevention,China, Rongshui County Disease Control and Prevention,China, Liucheng County Disease Control and Prevention,China, Jin Chengjiang Center for Disease Control and Prevention,China, National Institutes for Food and Drug Control, China, Air Force Military Medical University, China, Simoon Record Pharma Information Consulting Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01979900
Brief Title
Phase III Clinical Study of Efficacy and Safety of Vaccae™ to Prevent Tuberculosis
Official Title
Phase III Clinical Study of Efficacy and Safety of Mycobacterium Vaccae to Prevent Tuberculosis in High Risk Groups of Tuberculosis Infection
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
November 26, 2017 (Actual)
Study Completion Date
November 26, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Collaborators
Guangxi Center for Disease Control and Prevention, Liuzhou Center for Disease Control and Prevention,China, Rongshui County Disease Control and Prevention,China, Liucheng County Disease Control and Prevention,China, Jin Chengjiang Center for Disease Control and Prevention,China, National Institutes for Food and Drug Control, China, Air Force Military Medical University, China, Simoon Record Pharma Information Consulting Co., Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Mycobacterium Vaccae for Injection (Trade Name "Vaccae") is a kind of bio-products developed by Anhui Zhifei Longcom Biopharmaceutical Co.,Ltd.,and got "The New Drug Certificate "in 1999. Vaccae has been approved for adjuvant therapy of tuberculosis(TB), and is also the only recommended drug in TB immunotherapy by WHO. It was approved for production and sale by Anhui Zhifei Longcom Biopharmaceutical Co.,Ltd. in 2001, and got favourable comment in therapy of tuberculosis. The purpose of this study is to add new indications for Vaccae, mainly to prevent Tuberculosis for high risk groups of Tuberculosis Infection . In December 2012, China Food and Drug Administration approved of the plan "Phase III Clinical Study of Efficacy and Safety of Mycobacterium Vaccae to Prevent Tuberculosis in high risk groups of Tuberculosis Infection". In the test, 10,000 cases whose skin tests of PPD are strongly positive are enrolled. Using random, double-blind, and placebo-controlled methods, the study is carried out to evaluate the efficacy and safety of Vaccae in preventing Tuberculosis. Meanwhile, in this test, TB incidence and degree of pathological changes of experimental group are lower than that of control group, and no drug-related SAEs are reported in treatment groups.
Detailed Description
The Main Purpose of the Study: - Evaluation of efficacy of Vaccae to prevent Tuberculosis in high risk groups of Tuberculosis Infection. The Secondary Purpose of the Study: Evaluation of Lesion Degree ( Bacteriology Indicators, Cavity) of patients and its relationship with Skin Test results of TB-PPD after Injection of Vaccae into the high risk groups. Evaluation of Changes in Humoral Immunity and Cellular Immunologic Response Before and After Injection of Vaccae Test Hypothesis: In the test, TB incidence and degree of pathological changes of experimental group are lower than that of control group, and no drug-related SAEs are reported in treatment groups Blinding and Random: Using random, double-blind, and placebo-controlled methods, evaluation of the efficacy and safety of Vaccae. Using block randomization method, a random sequence was generated by the statistics personnel in Fourth Military Medical University Clinical Evaluation Center using SAS9.1.3 statistical software The Unblinding includes the first time of Unblinding and the second time of Unblinding. The first time of Unblinding only distinguish groups , and the second time of Unblinding will uncover the final Blind Codes. The Blind Codes of the design produce at one time, and unblinding will be carried out respectively at the first year and the second year after the beginning of the experiment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
TB Infection, Lesion Degree, Bacteriology Indicators, Cavity, Humoral Immunity, Cellular Immunologic Response

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10000 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vaccae
Arm Type
Experimental
Arm Description
Experiment group:One vial of Vaccae diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well, once every 2 weeks, 6 times totally.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo group:One vial of placebo diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well, once every 2 weeks, 6 times totally
Intervention Type
Drug
Intervention Name(s)
Vaccae
Other Intervention Name(s)
Mycobacterium vaccae for Injection
Intervention Description
One vial of Vaccae diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well, once every 2 weeks, 6 times totally.
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
Vaccae Lyophilized stabilizers
Intervention Description
One vial of placebo diluted with 1.0ml sterile water for injection, take deep coxal muscle injection after shaking well，once every 2 weeks, 6 times totally.
Primary Outcome Measure Information:
Title
The whole TB incidence after injection of Vaccae
Description
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease
Time Frame
Terminal Stage: two years after the last group of subjects enrolled
Secondary Outcome Measure Information:
Title
Lesion degree (Bacteriology indicators, cavity) of patients
Description
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease
Time Frame
two years after the last group of subjects enrolled or after observation of 76 cases of the disease
Title
Systemic and local reactions and adverse events
Description
within 30 days after last dosing
Time Frame
within 30 days after last dosing
Title
The relation between skin test results and paroxysm of TB-PPD
Description
Medium-term: one year after the last group of subjects enrolled or after observation of 38 cases of the disease, Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease
Time Frame
Terminal Stage: two years after the last group of subjects enrolled or after observation of 76 cases of the disease

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Aged from 15 to 65 years old, all genders. Skin test of Tuberculin Pure Protein Derivative (TB-PPD) is strongly positive ( the average diameter of PPD skin test induration is greater than or equal to 15mm,and（or）local blisters, necrosis). Agreed to participate in the test and sign the informed consent. Subjects agreed to participate in the experiments and voluntarily signed the informed consent. (guardians of 15-17- year-old subjects should agree, meanwhile). The subjects should comply with the requirements of the clinical trial protocol and be Followed. Have not participated in any other clinical trial for nearly three months. Women of childbearing age from 15 to 49 years should agree with urine pregnancy tests and take effective birth control measures in two years after the medication. Axillary temperature is normal. Exclusion Criteria: The first injection drug exclusion criteria : 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. Known allergy to experiment drugs People with history of specific diagnosis of TB, extrapulmonary tuberculosis or have been cured 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 Oral corticosteroids Patients who have been using oral corticosteroids for more than 1 week, or hormone medication in vitro for a long time Acute febrile illness and infection Pregnant or lactating women, or women who have birth plan in following 2 years Any other cases that may influence the test evaluation The second-sixth injection drug exclusion criteria : Subjects whose compliance is poor, and can not take medicine on time or according to the amount Patients who are using medicine and food that can influence the result Pregnant subjects during the test Patients who are reluctant to continue and require exit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guoai Si, Director
Organizational Affiliation
Jin Chengjiang Center for Diseases Control and Prevention, Hechi, Guangxi
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mingqiang Li, Director
Organizational Affiliation
Jin Chengjiang Center for Diseases Control and Prevention, Liuzhou, Guangxi
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Keshua Meng, Director
Organizational Affiliation
Rongshui County Diseases Control and Prevention, Liuzhou, Guangxi
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Debiao Qiao, Director
Organizational Affiliation
Liucheng County Diseases Control and Prevention, Liuzhou, Guangxi
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jin Chengjiang Center for Diseases Control and Prevention, Hechi, Guangxi
City
Hechi
State/Province
Guangxi
ZIP/Postal Code
547000
Country
China
Facility Name
Liucheng County Diseases Control and Prevention, Liuzhou, Guangxi
City
Liuzhou
State/Province
Guangxi
ZIP/Postal Code
545000
Country
China
Facility Name
Liuzhou Center for Diseases Control and Prevention, Liuzhou, Guangxi
City
Liuzhou
State/Province
Guangxi
ZIP/Postal Code
545000
Country
China
Facility Name
Rongshui County Diseases Control and Prevention, Liuzhou, Guangxi
City
Liuzhou
State/Province
Guangxi
ZIP/Postal Code
545000
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
17705981
Citation
Moran-Mendoza O, Marion SA, Elwood K, Patrick DM, FitzGerald JM. Tuberculin skin test size and risk of tuberculosis development: a large population-based study in contacts. Int J Tuberc Lung Dis. 2007 Sep;11(9):1014-20.
Results Reference
background
Links:
URL
https://wbca.cde.org.cn/wbca/clinmain.do?method=edit&ckmIdCode=2A2F055FEFF749918149A70D4830FE3C
Description
Center for drug evaluation, CFDA ,China

Learn more about this trial

Phase III Clinical Study of Efficacy and Safety of Vaccae™ to Prevent Tuberculosis

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