TuberculosisNCT01742364
Comparative Study of Bacille Calmette Guerin (BCG) Delivery Via Disposable Syringe Jet Injector and Needle & Syringe
A study testing Bioject ID Pen and Needle and syringe in people with Tuberculosis, run by PATH at 1 site in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Bioject ID Pen and Needle and syringe
- Type of treatment
- Vaccines, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteSouth Africa
- Study dates
- Dec 2012to Dec 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
- 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
- Participant must not have received BCG vaccination prior to enrolment.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Bioject ID Pen, Needle and syringe
- Keywords
- disposable syringe jet injector (DSJI), DSJI, BCG, tuberculosis, intradermal delivery, South Africa
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bioject ID PenDevice
Also called Disposable Syringe Jet Injector, DSJI, Jet Injector, ID Pen
Participants in this arm will receive a standard dose of BCG via the Bioject ID needle-free jet injector device (investigational administration technique).
Needle and syringeDevice
Participants in this arm will receive a standard dose of BCG via syringe and needle by the Mantoux technique (standard of care administration technique).
| Study group | Role | What they receive |
|---|---|---|
| Bioject Intradermal (ID) Pen | Experimental | Intradermal administration of BCG vaccine via the Bioject ID Pen. Receives: Device: Bioject ID Pen |
| Needle and syringe | Active comparator | Intradermal administration of BCG vaccine via needle and syringe. Receives: Device: Needle and syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 weeks
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.
Measured: 14 weeks
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.
Measured: 10 weeks post-vaccination
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.
Measured: 14 weeks post-vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- World Health Organization, University of Cape Town
- Responsible party
- Sponsor
- Investigators
- Hennie Geldenhuys, Principal investigator, South African Tuberculosis Vaccine Initiative
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01742364
- Sponsor's protocol ID
- HS 645
- Status last verified
- Dec 2013
- First submitted
- 30 Nov 2012
- Last updated
- 8 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01742364
- Acronym / sponsor ID
- HS 645
- Conditions
- Tuberculosis
- Keywords
- disposable syringe jet injector (DSJI), DSJI, BCG, tuberculosis, intradermal delivery, South Africa
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- World Health Organization, University of Cape Town
- Study start
- Dec 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Posted 8 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bioject Intradermal (ID) Pen | Experimental | Device: Bioject ID PenIntradermal administration of BCG vaccine via the Bioject ID Pen. |
| Needle and syringe | Active comparator | Device: Needle and syringeIntradermal administration of BCG vaccine via needle and syringe. |
Who may qualify
- Ages
- Up to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
Key exclusion criteria (10 listed)
- Neonate Stage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bioject ID PenAlso: Disposable Syringe Jet Injector, DSJI, Jet Injector, ID PenParticipants in this arm will receive a standard dose of BCG via the Bioject ID needle-free jet injector device (investigational administration technique). | Device | Bioject Intradermal (ID) Pen |
| Needle and syringeParticipants in this arm will receive a standard dose of BCG via syringe and needle by the Mantoux technique (standard of care administration technique). | Device | Needle and syringe |
Primary outcome
Injection Site Adverse Events (Following Injection)
Time frame: 14 weeks
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
Time frame: 14 weeks
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
Time frame: 10 weeks post-vaccination
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
Time frame: 14 weeks post-vaccination
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hennie Geldenhuys principal investigator
South African Tuberculosis Vaccine Initiative
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bioject ID Pen and Needle and syringe in people with Tuberculosis, run by PATH at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Injection Site Adverse Events (Following Injection) (time frame: 14 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2017.