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Clinical Study to Evaluate Safety and Immunogenicity of Bacillus Calmette-Guerin (BCG) Delivery Via Novel Micronjet600 Device Compared to Those Via Conventional Needle

Primary Purpose

Tuberculosis, BCG Vaccination

Status
Completed
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
BCG vaccination with MicronJet600
BCG vaccination with conventional needle
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, BCG vaccination

Eligibility Criteria

19 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 1) Subjects who voluntarily consented, after listening enough explanation for this study and the characteristics of medical devices and BCG vaccines.
  • 2) Adults from 19 to 35 years
  • 3) Tuberculin Skin Test negative
  • 4) QFT-GIT(QuantiFERON-TB Gold In-Tube) Test negative
  • 5) BMI from 19 to 35
  • 6) A person who is determined to be suitable for the clinical trial as a result of the screening test.

(Even if the physical, laboratory, imaging, or electrocardiogram results are out of the normal range, the subject may participate if he or she has provided a clear basis for participation at the discretion of the investigator.)

Exclusion Criteria:

  • 1) A person with a history of tuberculosis based on the medical history and chest radiograph, or who is suspected or confirmed to have a tuberculosis infection.
  • 2) A person who has active fever except for mild acute upper respiratory infection or localized skin infection other than the site to be treated, or who has a fever of 38 °C or more within 1 week before application of the medical devices for the clinical trial.
  • 3) A person who has not passed more than four weeks after the cure of virus infection (measles, mumps, chickenpox, and influenza).
  • 4) A case that the subject has skin abrasions, open wounds, wounds, or scars on the site where the medical devices for the clinical trial.
  • 5) A person who is unable to evaluate the local adverse effect because of tattoo, etc. on the site where the medical device for clinical trial is to be applied.
  • 6) Patients with clinically significant arrhythmia difficult to participate in the clinical trial.
  • 7) Patients with severe cardiac insufficiency (NYHA III and IV), a history of CABG(Coronary Artery Bypass Graft), and patients with cardiovascular diseases who are considered to be difficult to participate in the clinical trial.
  • 8) A person with a known history of diabetes or a person whose diabetes was confirmed by a test.
  • 9) Patients with hepatitis C or hepatitis B (in the case of hepatitis virus, healthy carriers may be participated at the discretion of the investigator) or positive for the serum test for human immunodeficiency virus (HIV).
  • 10) Patients with severe immunosuppressive disease: congenital immunodeficiency such as severe combined immunodeficiency (SCID); leukemia; lymphoma, etc.
  • 11) Patients with chronic renal insufficiency
  • 12) A history of malignant tumors within 3 years excluding thyroid cancer (papillary, follicular, medullary types corresponding to Stage I or II), basal cell or squamous cell carcinoma on the skin, CIN(cervical intraepithelial neoplasia) and CIS(Carcinoma in situ) of the cervix, and intraepithelial carcinoma in other sites.
  • 13) A case that a person has hypersensitivity or anamnesis for constitutivity constituting BCG.
  • 14) Subjects who have not passed the predetermined period after receiving medication or treatment before the subjects participate in the clinical trial. (Refer to section 5.2.3.2)
  • 15) Patients receiving concomitant medications (Refer to section 5.2.3.3)
  • 16) A person who is unable to participate in the clinical trial period (about 6 months).
  • 17) Patients scheduled for major surgery during the clinical trial.
  • 18) A person who has a history of alcohol and other substance abuse for 6 months before screening.
  • 19) Pregnant women or lactating women who are not willing to stop breastfeeding.
  • 20) If the following are not applicable, (That is, you can only participate if):

    1. Women(female?) in the menopause (non-therapy-induced amenorrhea for more than 12 months)
    2. Infertility due to surgery (without ovaries and/or uterus)
    3. If the female subject have sexual intercourse with only one male partner who has been confirmed to have no semen after fertilization
    4. Female subjects who have agreed to abstinence during the clinical trial period

      • If the subject is assured of abstinence throughout the clinical trial period (only if abstinence is voluntarily selected by the subject and abstinence is consistent with the general lifestyle of the subject: e.g., Priest)

        • However, intermittent abstinence (e.g., ovulation, symptothermal method, or late ovulation) or external ejaculation is not a case of consent for abstinence.
    5. In the case of a woman who is in childbearing years, a woman who decides to use an effective method of contraception during the clinical trial period:

      • Oral contraception

        • Patch for contraception

          • Intrauterine Contraceptive Device (IUD)

            • Implant for contraception

              • Injection for contraception (Time-released type)

                • Hormone device in the uterus

                  • Tubal ligation and infertility surgery
  • 21) Patient who has not passed 30 days since the date of signing the agreement of the previous clinical trial or who is currently participating in other clinical trial
  • 22) Other diseases other than those listed above that the investigator deems inappropriate

Sites / Locations

  • Department of Internal Medicine, Yonsei University College of Medicine Division of Pulmonology, Severance Hospital, Yonsei University Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

MicronJet600

Conventional needle

Arm Description

BCG vaccination with MicronJet600

BCG vaccination with conventional needle

Outcomes

Primary Outcome Measures

Adverse Events
Frequency and characteristics of adverse events after applying medical devices for clinical trials (aspect, materiality, results, etc.)
Adverse Events
Frequency and characteristics of adverse events after applying medical devices for clinical trials (aspect, materiality, results, etc.)

Secondary Outcome Measures

Average of usability VAS for medical device user
The descriptive statistics (number of subjects, mean, standard deviation, median, minimum and maximum values) for the VAS(Visual Analogue Scale) scores measured at the time of the clinical device VAS(visual analogue scale) :0(no paine)~10(wort possible, unbearable, excruciating pain). If necessary, a significance assessment will be performed through an independent t-test or Wilcoxon rank-sum test, and generalized linear model.
Spot Forming Unit (SFU) per PBMC(Peripheral Blood Mononuclear Cells)
Ex vivo IFN(Interferon) γ ELISpot analysis to measure the number of T cells that secrete cytokines by mycobacterial antigen-specific immune response
Spot Forming Unit (SFU) per PBMC
Ex vivo IFN γ ELISpot analysis to measure the number of T cells that secrete cytokines by mycobacterial antigen-specific immune response
Delta log10 CFU
Delta log 10 CFU at each time point evaluated by Ex vivo Mycobacterial Growth Inhibition Assay (MGIA). Delta log10 CFU=log(CFU count of each sample tube/CFU count of the growth control tube/incubation indays)
Delta log10 CFU
Delta log 10 CFU at each time point evaluated by Ex vivo Mycobacterial Growth Inhibition Assay (MGIA). Delta log10 CFU=log(CFU count of each sample tube/CFU count of the growth control tube/incubation indays)
Mycobacterial antigen specific T-cell
For intracellular cytokine staining (ICS) assay testing, the investigators will evaluate IFN-γ and TNF(Tumor Necrosis Factor)-α as intracellular cytokines. To assess ICS, blood samples were drawn before PPD(Purified protein derivative) administration at Visit 1. ICS assay will be performed using FACS(fluorescence activated cell sorting)(Fluorescence Activated Cell Sorting). The fraction of cells that are positive for any of cytokines measured at each point will be evaluated by total T cells, T4 and T8 subtype cells.
Mycobacterial antigen specific T-cell
For intracellular cytokine staining (ICS) assay testing, the investigators will evaluate IFN-γ and TNF-α as intracellular cytokines. To assess ICS, blood samples were drawn before PPD administration at Visit 5. ICS assay will be performed using FACS(Fluorescence Activated Cell Sorting). The fraction of cells that are positive for any of cytokines measured at each point will be evaluated by total T cells, T4 and T8 subtype cells.
PPD test result (positive or negative) after application of medical device for clinical trial
The number of test subjects who showed positive reactions at the time of evaluation (V6) will be presented for each group.
Diameter of induration (mm) or presence or absence of blister
Descriptive statistics (number of subjects, mean, standard deviation, median, minimum, and maximum values) for the diameter of the mandible measured at the time of administration of the medical device for clinical use are presented for each application group.
The diameter of the wheal
The diameter of the wheal at the injection site immediately after BCG vaccination If necessary, a significance assessment will be performed through an independent t-test or Wilcoxon rank-sum test, and generalized linear model.
Fraction of subjects eligible for each grade in the injection fluid leakage assessment at the injection site
The number of test subjects to the degree of leakage assessment observed following the application of the clinical trial medical device will be presented for each application group. If necessary, a significance assessment will be performed through a chi-square test or Fisher's exact test.
Progress of normal reaction after BCG injection
The normal reaction of the injected site observed after application of the medical device for clinical use will be indicated for each application group.
Diameter of the scar after BCG injection

Full Information

First Posted
August 5, 2019
Last Updated
December 3, 2019
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT04064554
Brief Title
Clinical Study to Evaluate Safety and Immunogenicity of Bacillus Calmette-Guerin (BCG) Delivery Via Novel Micronjet600 Device Compared to Those Via Conventional Needle
Official Title
A Prospective, Randomized, Open-label, Single-centered Clinical Study to Evaluate Safety and Immunogenicity of Bacillus Calmette-Guerin (BCG) Delivery Via Novel Micronjet600 Device Compared to Those Via Conventional Needle
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
September 11, 2019 (Actual)
Study Completion Date
September 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate safety and immunogenicity of Bacillus Calmette-Guerin (BCG) delivery via Novel Micronjet600 device compared to those via conventional needle.
Detailed Description
This study is designed as prospective, randomized, open-label, single-centered. In this study, healthy adults who meet inclusion criteria will be randomized and receive a BCG vaccine either using a conventional needle or MicronJet600 device. After vaccination, adverse events and progress will be observed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, BCG Vaccination
Keywords
Tuberculosis, BCG vaccination

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Experimental: BCG vaccination with MicronJet600 Comparator: BCG vaccination with conventional needle
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MicronJet600
Arm Type
Experimental
Arm Description
BCG vaccination with MicronJet600
Arm Title
Conventional needle
Arm Type
Active Comparator
Arm Description
BCG vaccination with conventional needle
Intervention Type
Device
Intervention Name(s)
BCG vaccination with MicronJet600
Intervention Description
BCG vaccination with MicronJet600
Intervention Type
Device
Intervention Name(s)
BCG vaccination with conventional needle
Intervention Description
BCG vaccination with conventional needle
Primary Outcome Measure Information:
Title
Adverse Events
Description
Frequency and characteristics of adverse events after applying medical devices for clinical trials (aspect, materiality, results, etc.)
Time Frame
Visit 3(day 1, after vaccination) ~ Visit 6 (from 2 or 3 day of the Visit 5(day 85±7))
Title
Adverse Events
Description
Frequency and characteristics of adverse events after applying medical devices for clinical trials (aspect, materiality, results, etc.)
Time Frame
during study period (Visit 3~Visit 6, 96 days)
Secondary Outcome Measure Information:
Title
Average of usability VAS for medical device user
Description
The descriptive statistics (number of subjects, mean, standard deviation, median, minimum and maximum values) for the VAS(Visual Analogue Scale) scores measured at the time of the clinical device VAS(visual analogue scale) :0(no paine)~10(wort possible, unbearable, excruciating pain). If necessary, a significance assessment will be performed through an independent t-test or Wilcoxon rank-sum test, and generalized linear model.
Time Frame
Visit 3 (day 1)
Title
Spot Forming Unit (SFU) per PBMC(Peripheral Blood Mononuclear Cells)
Description
Ex vivo IFN(Interferon) γ ELISpot analysis to measure the number of T cells that secrete cytokines by mycobacterial antigen-specific immune response
Time Frame
Visit 1(day -28~2)
Title
Spot Forming Unit (SFU) per PBMC
Description
Ex vivo IFN γ ELISpot analysis to measure the number of T cells that secrete cytokines by mycobacterial antigen-specific immune response
Time Frame
Visit 5(day 85±7)
Title
Delta log10 CFU
Description
Delta log 10 CFU at each time point evaluated by Ex vivo Mycobacterial Growth Inhibition Assay (MGIA). Delta log10 CFU=log(CFU count of each sample tube/CFU count of the growth control tube/incubation indays)
Time Frame
Visit 1(day -28~2)
Title
Delta log10 CFU
Description
Delta log 10 CFU at each time point evaluated by Ex vivo Mycobacterial Growth Inhibition Assay (MGIA). Delta log10 CFU=log(CFU count of each sample tube/CFU count of the growth control tube/incubation indays)
Time Frame
Visit 5(day 85±7)
Title
Mycobacterial antigen specific T-cell
Description
For intracellular cytokine staining (ICS) assay testing, the investigators will evaluate IFN-γ and TNF(Tumor Necrosis Factor)-α as intracellular cytokines. To assess ICS, blood samples were drawn before PPD(Purified protein derivative) administration at Visit 1. ICS assay will be performed using FACS(fluorescence activated cell sorting)(Fluorescence Activated Cell Sorting). The fraction of cells that are positive for any of cytokines measured at each point will be evaluated by total T cells, T4 and T8 subtype cells.
Time Frame
Visit 1(day -28~2)
Title
Mycobacterial antigen specific T-cell
Description
For intracellular cytokine staining (ICS) assay testing, the investigators will evaluate IFN-γ and TNF-α as intracellular cytokines. To assess ICS, blood samples were drawn before PPD administration at Visit 5. ICS assay will be performed using FACS(Fluorescence Activated Cell Sorting). The fraction of cells that are positive for any of cytokines measured at each point will be evaluated by total T cells, T4 and T8 subtype cells.
Time Frame
Visit 5(day 85±7)
Title
PPD test result (positive or negative) after application of medical device for clinical trial
Description
The number of test subjects who showed positive reactions at the time of evaluation (V6) will be presented for each group.
Time Frame
Visit 6 (from 2 or 3 day of the Visit 5(day 85±7))
Title
Diameter of induration (mm) or presence or absence of blister
Description
Descriptive statistics (number of subjects, mean, standard deviation, median, minimum, and maximum values) for the diameter of the mandible measured at the time of administration of the medical device for clinical use are presented for each application group.
Time Frame
Visit 6 (from 2 or 3 day of the Visit 5(day 85±7))
Title
The diameter of the wheal
Description
The diameter of the wheal at the injection site immediately after BCG vaccination If necessary, a significance assessment will be performed through an independent t-test or Wilcoxon rank-sum test, and generalized linear model.
Time Frame
Visit 3 (day 1, after vaccination)
Title
Fraction of subjects eligible for each grade in the injection fluid leakage assessment at the injection site
Description
The number of test subjects to the degree of leakage assessment observed following the application of the clinical trial medical device will be presented for each application group. If necessary, a significance assessment will be performed through a chi-square test or Fisher's exact test.
Time Frame
Visit 3 (day 1, immediately after vaccination)
Title
Progress of normal reaction after BCG injection
Description
The normal reaction of the injected site observed after application of the medical device for clinical use will be indicated for each application group.
Time Frame
Visit 3(day 1, after vaccination) ~ Visit 6 (from 2 or 3 day of the Visit 5(day 85±7))
Title
Diameter of the scar after BCG injection
Time Frame
Visit 3(day 1, after vaccination) ~ Visit 6 (from 2 or 3 day of the Visit 5(day 85±7))

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 1) Subjects who voluntarily consented, after listening enough explanation for this study and the characteristics of medical devices and BCG vaccines. 2) Adults from 19 to 35 years 3) Tuberculin Skin Test negative 4) QFT-GIT(QuantiFERON-TB Gold In-Tube) Test negative 5) BMI from 19 to 35 6) A person who is determined to be suitable for the clinical trial as a result of the screening test. (Even if the physical, laboratory, imaging, or electrocardiogram results are out of the normal range, the subject may participate if he or she has provided a clear basis for participation at the discretion of the investigator.) Exclusion Criteria: 1) A person with a history of tuberculosis based on the medical history and chest radiograph, or who is suspected or confirmed to have a tuberculosis infection. 2) A person who has active fever except for mild acute upper respiratory infection or localized skin infection other than the site to be treated, or who has a fever of 38 °C or more within 1 week before application of the medical devices for the clinical trial. 3) A person who has not passed more than four weeks after the cure of virus infection (measles, mumps, chickenpox, and influenza). 4) A case that the subject has skin abrasions, open wounds, wounds, or scars on the site where the medical devices for the clinical trial. 5) A person who is unable to evaluate the local adverse effect because of tattoo, etc. on the site where the medical device for clinical trial is to be applied. 6) Patients with clinically significant arrhythmia difficult to participate in the clinical trial. 7) Patients with severe cardiac insufficiency (NYHA III and IV), a history of CABG(Coronary Artery Bypass Graft), and patients with cardiovascular diseases who are considered to be difficult to participate in the clinical trial. 8) A person with a known history of diabetes or a person whose diabetes was confirmed by a test. 9) Patients with hepatitis C or hepatitis B (in the case of hepatitis virus, healthy carriers may be participated at the discretion of the investigator) or positive for the serum test for human immunodeficiency virus (HIV). 10) Patients with severe immunosuppressive disease: congenital immunodeficiency such as severe combined immunodeficiency (SCID); leukemia; lymphoma, etc. 11) Patients with chronic renal insufficiency 12) A history of malignant tumors within 3 years excluding thyroid cancer (papillary, follicular, medullary types corresponding to Stage I or II), basal cell or squamous cell carcinoma on the skin, CIN(cervical intraepithelial neoplasia) and CIS(Carcinoma in situ) of the cervix, and intraepithelial carcinoma in other sites. 13) A case that a person has hypersensitivity or anamnesis for constitutivity constituting BCG. 14) Subjects who have not passed the predetermined period after receiving medication or treatment before the subjects participate in the clinical trial. (Refer to section 5.2.3.2) 15) Patients receiving concomitant medications (Refer to section 5.2.3.3) 16) A person who is unable to participate in the clinical trial period (about 6 months). 17) Patients scheduled for major surgery during the clinical trial. 18) A person who has a history of alcohol and other substance abuse for 6 months before screening. 19) Pregnant women or lactating women who are not willing to stop breastfeeding. 20) If the following are not applicable, (That is, you can only participate if): Women(female?) in the menopause (non-therapy-induced amenorrhea for more than 12 months) Infertility due to surgery (without ovaries and/or uterus) If the female subject have sexual intercourse with only one male partner who has been confirmed to have no semen after fertilization Female subjects who have agreed to abstinence during the clinical trial period If the subject is assured of abstinence throughout the clinical trial period (only if abstinence is voluntarily selected by the subject and abstinence is consistent with the general lifestyle of the subject: e.g., Priest) However, intermittent abstinence (e.g., ovulation, symptothermal method, or late ovulation) or external ejaculation is not a case of consent for abstinence. In the case of a woman who is in childbearing years, a woman who decides to use an effective method of contraception during the clinical trial period: Oral contraception Patch for contraception Intrauterine Contraceptive Device (IUD) Implant for contraception Injection for contraception (Time-released type) Hormone device in the uterus Tubal ligation and infertility surgery 21) Patient who has not passed 30 days since the date of signing the agreement of the previous clinical trial or who is currently participating in other clinical trial 22) Other diseases other than those listed above that the investigator deems inappropriate
Facility Information:
Facility Name
Department of Internal Medicine, Yonsei University College of Medicine Division of Pulmonology, Severance Hospital, Yonsei University Health System
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No

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Clinical Study to Evaluate Safety and Immunogenicity of Bacillus Calmette-Guerin (BCG) Delivery Via Novel Micronjet600 Device Compared to Those Via Conventional Needle

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