Back to resultsComparative Study of Bacille Calmette Guerin (BCG) Delivery Via Disposable Syringe Jet Injector and Needle & Syringe
Primary Purpose
Tuberculosis
Status
Completed
Phase
Not Applicable
Locations
South Africa
Study Type
Interventional
Intervention
Bioject ID Pen
Needle and syringe
Sponsored by
About this trial
This is an interventional prevention trial for Tuberculosis focused on measuring disposable syringe jet injector (DSJI), DSJI, BCG, tuberculosis, intradermal delivery, South Africa
Eligibility Criteria
Adult stage
Inclusion criteria:
- Male or female, age 18 to 50 years.
- Written informed consent, including permission for access to medical records and an HIV test.
- Available for study follow up and display a willingness and capacity to comply to study procedures.
- In good general health, as assessed by medical history and a focused physical examination.
- HIV test (rapid test, ELISA [enzyme-linked immunosorbent assay], or PCR [polymerase chain reaction]) negative.
- Quantiferon®-TB Gold (Cellestis) test for latent TB infection negative within 2 weeks of enrolment.
- BCG vaccination at birth as confirmed by history or the presence of a BCG scar.
- In the case of female participants, a negative urine or serum pregnancy test at enrolment, and not pregnant or lactating. Evidence of contraception is not required since BCG is not contra-indicated in pregnancy.
Exclusion criteria:
- A history or evidence of a significant or chronic medical condition or disease.
- Skin condition, bruising or birth mark at the intended injection site.
- History of previous active tuberculosis (TB) disease or current active TB disease.
- History of a household contact with active TB disease who has received less than 2 months treatment.
Neonate Stage
Inclusion criteria:
- Male or female neonates within 48 hours of birth.
- Written informed consent, including permission to access medical records and results of antenatal HIV tests.
- Infant participants and their caregivers available for study follow-up and display the willingness and capacity to comply with study procedures.
- Neonates must be in good general health as assessed by medical history during pregnancy and delivery, and focused physical examination.
- Birth weight more than or equal to 2500 grams.
- Apgar score at 5 minutes more than or equal to 7.
- A maternal HIV test result (rapid test, ELISA or PCR) taken during pregnancy must be available, documented and negative.
Exclusion criteria:
- Participant must not have received BCG vaccination prior to enrolment.
- Significant antenatal or intrapartum complications that may affect the health of the neonate.
- Skin condition, bruising or birth mark at the intended injection site.
- Maternal HIV test (rapid test, ELISA or PCR) not performed antenatally, HIV test results not available, or HIV test result known positive.
- Maternal history of current active TB, or other household contact with known active TB disease who has received less than 2 months of treatment.
Sites / Locations
- SATVI, University of Cape Town
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Bioject Intradermal (ID) Pen
Needle and syringe
Arm Description
Intradermal administration of BCG vaccine via the Bioject ID Pen.
Intradermal administration of BCG vaccine via needle and syringe.
Outcomes
Primary Outcome Measures
Injection Site Adverse Events (Following Injection)
Injection site adverse events including redness, swelling, induration, tenderness, ulceration, fluctuation , drainage, laceration, bruising, and scarring will be monitored for up to fourteen weeks following vaccination.
Systemic Adverse Events
Systemic adverse events, solicited and unsolicited, including symptoms of lethargy, disrupted feeding patterns, fever, lymphadenopathy, rash, or any other physical abnormalities will be monitored for up to fourteen weeks following vaccination.
Short Term Whole Blood Intracellular Cytokine Staining Assay for BCG-specific CD4 (Cluster of Differentiation 4) T-cells
BCG-specific immunogenicity was tested in infants only, since they are the target study population and BCG immunogenicity in adults is known to be different from that in infants.
Utilizing a whole-blood intracellular cytokine staining (ICS) assay, we analyzed cytokine co-expression patterns by BCG-specific CD4 and CD8 T-cells. Briefly, 0.5 ml heparinized whole blood was incubated for 12 hours with BCG, no antigen or phytohemagglutinin (PHA) in the presence of anti-CD28 and anti-CD49d, with the last 5 hours including Brefeldin A prior to treating with BD FACS™ Lysing Solution and cryopreservation. Cells were batch-thawed, permeabilized with BD Perm/Wash™ buffer, and stained with fluorescent antibodies. At least 120,000 CD3+CD4+ T-cells were acquired for the no-antigen and BCG samples on a BD™ LSR II flow cytometer.
Short Term Whole Blood Intracellular Cytokine Staining Assay for BCG-specific CD4 T-cells
BCG-specific immunogenicity was tested in infants only, since they are the target study population and BCG immunogenicity in adults is known to be different from that in infants.
Utilizing a whole-blood intracellular cytokine staining (ICS) assay, we analyzed cytokine co-expression patterns by BCG-specific CD4 and CD8 T-cells. Briefly, 0.5 ml heparinized whole blood was incubated for 12 hours with BCG, no antigen or phytohemagglutinin (PHA) in the presence of anti-CD28 and anti-CD49d, with the last 5 hours including Brefeldin A prior to treating with BD FACS™ Lysing Solution and cryopreservation. Cells were batch-thawed, permeabilized with BD Perm/Wash™ buffer, and stained with fluorescent antibodies. At least 120,000 CD3+CD4+ T-cells were acquired for the no-antigen and BCG samples on a BD™ LSR II flow cytometer.
Secondary Outcome Measures
Full Information
NCT ID
NCT01742364
First Posted
November 30, 2012
Last Updated
December 15, 2016
Sponsor
PATH
Collaborators
World Health Organization, University of Cape Town
1. Study Identification
Unique Protocol Identification Number
NCT01742364
Brief Title
Comparative Study of Bacille Calmette Guerin (BCG) Delivery Via Disposable Syringe Jet Injector and Needle & Syringe
Official Title
A Randomized Clinical Trial in Adults and Newborns to Compare the Safety, Reactogenicity and Immunogenicity of BCG Administration Via a Disposable Syringe Jet Injector (DSJI) to BCG Administration Via Syringe and Needle
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
World Health Organization, University of Cape Town
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is designed to test the hypothesis that BCG administration via jet injector will produce a comparable immune response and that there will be no significant differences in safety or reactogenicity between BCG administration via jet injector and needle and syringe.
The primary objectives of this study are to...
Compare the safety and reactogenicity of BCG administered intradermally by a jet injector device in adults and infants, to BCG administered intradermally by needle and syringe;
Compare the specific T cell immunity in neonates vaccinated with BCG via the jet injector device to infants vaccinated with BCG via needle and syringe.
Detailed Description
A randomized, controlled, partially blinded clinical trial in 2 stages (adult stage, infant stage) will be applied at a single site.
The first stage will include thirty (30) adult participants. The Data Safety Monitoring Board (DSMB) will evaluate the reactogenicity and safety data for all 30 adults up to day 28 after vaccination. Pending a favourable safety review by the DSMB, the second stage in sixty-six (66) newborn participants will commence. Potential adult and infant participants will be screened prior to enrolment to apply inclusion and exclusion criteria.Note that as the adult stage was a pilot, only results of the infant study are presented here.
In each of the stages half of the study population (15 adults, 33 neonates) will receive BCG via conventional syringe and needle (standard of care administration technique), and half (15 adults, 33 neonates) will receive BCG via jet injector (investigational administration technique). A single and standard volume and dose of BCG will be administered per the package insert. Neonates will receive their BCG shortly after birth.
The occurrence of injection site reactogenicity events and systemic adverse events will be compared between study groups in both adults and neonates. In the neonate stage, BCG and M.tb specific immunogenicity will also be compared between study groups.
For the adult stage the vaccinator and participant will be unblinded to study arm allocation. For the infant stage, the vaccinator will be unblinded but the participant caregiver will be blinded. For both the adult and infant stages the follow-up team will be blinded to study arm allocation. The laboratory will be blinded to study arm allocation for the infant stage immunogenicity assays.
The trial will be conducted at the field site of the South African Tuberculosis Vaccine Initiative (SATVI) in the Cape Winelands East district of the Western Cape of South Africa. Recruitment and vaccination of neonates will take place at 1 or more of the state public healthcare antenatal clinics and birthing units in the area. Recruitment and vaccination of adults, as well as follow-up of adults and the neonates/infants will take place on the SATVI field site premises, or on the premises of the public healthcare clinic. All study procedures, including vaccination, will be performed by SATVI study staff.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
disposable syringe jet injector (DSJI), DSJI, BCG, tuberculosis, intradermal delivery, South Africa
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bioject Intradermal (ID) Pen
Arm Type
Experimental
Arm Description
Intradermal administration of BCG vaccine via the Bioject ID Pen.
Arm Title
Needle and syringe
Arm Type
Active Comparator
Arm Description
Intradermal administration of BCG vaccine via needle and syringe.
Intervention Type
Device
Intervention Name(s)
Bioject ID Pen
Other Intervention Name(s)
Disposable Syringe Jet Injector, DSJI, Jet Injector, ID Pen
Intervention Description
Participants in this arm will receive a standard dose of BCG via the Bioject ID needle-free jet injector device (investigational administration technique).
Intervention Type
Device
Intervention Name(s)
Needle and syringe
Intervention Description
Participants in this arm will receive a standard dose of BCG via syringe and needle by the Mantoux technique (standard of care administration technique).
Primary Outcome Measure Information:
Title
Injection Site Adverse Events (Following Injection)
Description
Injection site adverse events including redness, swelling, induration, tenderness, ulceration, fluctuation , drainage, laceration, bruising, and scarring will be monitored for up to fourteen weeks following vaccination.
Time Frame
14 weeks
Title
Systemic Adverse Events
Description
Systemic adverse events, solicited and unsolicited, including symptoms of lethargy, disrupted feeding patterns, fever, lymphadenopathy, rash, or any other physical abnormalities will be monitored for up to fourteen weeks following vaccination.
Time Frame
14 weeks
Title
Short Term Whole Blood Intracellular Cytokine Staining Assay for BCG-specific CD4 (Cluster of Differentiation 4) T-cells
Description
BCG-specific immunogenicity was tested in infants only, since they are the target study population and BCG immunogenicity in adults is known to be different from that in infants.
Utilizing a whole-blood intracellular cytokine staining (ICS) assay, we analyzed cytokine co-expression patterns by BCG-specific CD4 and CD8 T-cells. Briefly, 0.5 ml heparinized whole blood was incubated for 12 hours with BCG, no antigen or phytohemagglutinin (PHA) in the presence of anti-CD28 and anti-CD49d, with the last 5 hours including Brefeldin A prior to treating with BD FACS™ Lysing Solution and cryopreservation. Cells were batch-thawed, permeabilized with BD Perm/Wash™ buffer, and stained with fluorescent antibodies. At least 120,000 CD3+CD4+ T-cells were acquired for the no-antigen and BCG samples on a BD™ LSR II flow cytometer.
Time Frame
10 weeks post-vaccination
Title
Short Term Whole Blood Intracellular Cytokine Staining Assay for BCG-specific CD4 T-cells
Description
BCG-specific immunogenicity was tested in infants only, since they are the target study population and BCG immunogenicity in adults is known to be different from that in infants.
Utilizing a whole-blood intracellular cytokine staining (ICS) assay, we analyzed cytokine co-expression patterns by BCG-specific CD4 and CD8 T-cells. Briefly, 0.5 ml heparinized whole blood was incubated for 12 hours with BCG, no antigen or phytohemagglutinin (PHA) in the presence of anti-CD28 and anti-CD49d, with the last 5 hours including Brefeldin A prior to treating with BD FACS™ Lysing Solution and cryopreservation. Cells were batch-thawed, permeabilized with BD Perm/Wash™ buffer, and stained with fluorescent antibodies. At least 120,000 CD3+CD4+ T-cells were acquired for the no-antigen and BCG samples on a BD™ LSR II flow cytometer.
Time Frame
14 weeks post-vaccination
Other Pre-specified Outcome Measures:
Title
Diameter of Skin Bleb
Time Frame
Immediately post-vaccination
Title
Fluid Leakage on Skin at Injection Site
Time Frame
Immediately post-vaccination
10. Eligibility
Sex
All
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Adult stage
Inclusion criteria:
Male or female, age 18 to 50 years.
Written informed consent, including permission for access to medical records and an HIV test.
Available for study follow up and display a willingness and capacity to comply to study procedures.
In good general health, as assessed by medical history and a focused physical examination.
HIV test (rapid test, ELISA [enzyme-linked immunosorbent assay], or PCR [polymerase chain reaction]) negative.
Quantiferon®-TB Gold (Cellestis) test for latent TB infection negative within 2 weeks of enrolment.
BCG vaccination at birth as confirmed by history or the presence of a BCG scar.
In the case of female participants, a negative urine or serum pregnancy test at enrolment, and not pregnant or lactating. Evidence of contraception is not required since BCG is not contra-indicated in pregnancy.
Exclusion criteria:
A history or evidence of a significant or chronic medical condition or disease.
Skin condition, bruising or birth mark at the intended injection site.
History of previous active tuberculosis (TB) disease or current active TB disease.
History of a household contact with active TB disease who has received less than 2 months treatment.
Neonate Stage
Inclusion criteria:
Male or female neonates within 48 hours of birth.
Written informed consent, including permission to access medical records and results of antenatal HIV tests.
Infant participants and their caregivers available for study follow-up and display the willingness and capacity to comply with study procedures.
Neonates must be in good general health as assessed by medical history during pregnancy and delivery, and focused physical examination.
Birth weight more than or equal to 2500 grams.
Apgar score at 5 minutes more than or equal to 7.
A maternal HIV test result (rapid test, ELISA or PCR) taken during pregnancy must be available, documented and negative.
Exclusion criteria:
Participant must not have received BCG vaccination prior to enrolment.
Significant antenatal or intrapartum complications that may affect the health of the neonate.
Skin condition, bruising or birth mark at the intended injection site.
Maternal HIV test (rapid test, ELISA or PCR) not performed antenatally, HIV test results not available, or HIV test result known positive.
Maternal history of current active TB, or other household contact with known active TB disease who has received less than 2 months of treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hennie Geldenhuys
Organizational Affiliation
South African Tuberculosis Vaccine Initiative
Official's Role
Principal Investigator
Facility Information:
Facility Name
SATVI, University of Cape Town
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
No
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Comparative Study of Bacille Calmette Guerin (BCG) Delivery Via Disposable Syringe Jet Injector and Needle & Syringe
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