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

This study has been completed.
Sponsor:
Collaborators:
World Health Organization
University of Cape Town
Information provided by (Responsible Party):
PATH
ClinicalTrials.gov Identifier:
NCT01742364
First received: November 30, 2012
Last updated: December 15, 2016
Last verified: December 2013
  Purpose

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.

Condition Intervention
Tuberculosis
Device: Bioject ID Pen
Device: Needle and syringe

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by PATH:

Primary Outcome Measures:
  • 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.



Other Outcome Measures:
  • Diameter of Skin Bleb [ Time Frame: Immediately post-vaccination ]
  • Fluid Leakage on Skin at Injection Site [ Time Frame: Immediately post-vaccination ]

Enrollment: 96
Study Start Date: December 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bioject Intradermal (ID) Pen
Intradermal administration of BCG vaccine via the Bioject ID Pen.
Device: Bioject 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).
Other Names:
  • Disposable Syringe Jet Injector
  • DSJI
  • Jet Injector
  • ID Pen
Active Comparator: Needle and syringe
Intradermal administration of BCG vaccine via needle and syringe.
Device: Needle and syringe
Participants in this arm will receive a standard dose of BCG via syringe and needle by the Mantoux technique (standard of care administration technique).

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.

  Eligibility

Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Adult stage

  • Inclusion criteria:

    1. Male or female, age 18 to 50 years.
    2. Written informed consent, including permission for access to medical records and an HIV test.
    3. Available for study follow up and display a willingness and capacity to comply to study procedures.
    4. In good general health, as assessed by medical history and a focused physical examination.
    5. HIV test (rapid test, ELISA [enzyme-linked immunosorbent assay], or PCR [polymerase chain reaction]) negative.
    6. Quantiferon®-TB Gold (Cellestis) test for latent TB infection negative within 2 weeks of enrolment.
    7. BCG vaccination at birth as confirmed by history or the presence of a BCG scar.
    8. 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:

    1. A history or evidence of a significant or chronic medical condition or disease.
    2. Skin condition, bruising or birth mark at the intended injection site.
    3. History of previous active tuberculosis (TB) disease or current active TB disease.
    4. History of a household contact with active TB disease who has received less than 2 months treatment.

Neonate Stage

  • Inclusion criteria:

    1. Male or female neonates within 48 hours of birth.
    2. Written informed consent, including permission to access medical records and results of antenatal HIV tests.
    3. Infant participants and their caregivers available for study follow-up and display the willingness and capacity to comply with study procedures.
    4. Neonates must be in good general health as assessed by medical history during pregnancy and delivery, and focused physical examination.
    5. Birth weight more than or equal to 2500 grams.
    6. Apgar score at 5 minutes more than or equal to 7.
    7. A maternal HIV test result (rapid test, ELISA or PCR) taken during pregnancy must be available, documented and negative.
  • Exclusion criteria:

    1. Participant must not have received BCG vaccination prior to enrolment.
    2. Significant antenatal or intrapartum complications that may affect the health of the neonate.
    3. Skin condition, bruising or birth mark at the intended injection site.
    4. Maternal HIV test (rapid test, ELISA or PCR) not performed antenatally, HIV test results not available, or HIV test result known positive.
    5. Maternal history of current active TB, or other household contact with known active TB disease who has received less than 2 months of treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01742364

Locations
South Africa
SATVI, University of Cape Town
Cape Town, South Africa, 7925
Sponsors and Collaborators
PATH
World Health Organization
University of Cape Town
Investigators
Principal Investigator: Hennie Geldenhuys South African Tuberculosis Vaccine Initiative
  More Information

Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT01742364     History of Changes
Other Study ID Numbers: HS 645 
Study First Received: November 30, 2012
Results First Received: April 6, 2016
Last Updated: December 15, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by PATH:
disposable syringe jet injector (DSJI)
DSJI
BCG
tuberculosis
intradermal delivery
South Africa

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on February 17, 2017