Comparative Study of Bacille Calmette Guerin (BCG) Delivery Via Disposable Syringe Jet Injector and Needle & Syringe

Not Applicable

Completed

Conditions: Tuberculosis

Interventions: Device: Bioject ID Pen
Device: Needle and syringe

Registration Number: NCT01742364

Lead Sponsor: PATH

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...

1. 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;

2. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 96

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bioject Intradermal (ID) Pen	Bioject ID Pen	Intradermal administration of BCG vaccine via the Bioject ID Pen.
Needle and syringe	Needle and syringe	Intradermal administration of BCG vaccine via needle and syringe.

Primary Outcome Measures

Name	Time	Method
Systemic Adverse Events	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 T-cells	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.
Injection Site Adverse Events (Following Injection)	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.
Short Term Whole Blood Intracellular Cytokine Staining Assay for BCG-specific CD4 (Cluster of Differentiation 4) T-cells	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.