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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- PATH
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Systemic Adverse Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- — 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Bioject Intradermal (ID) Pen
Intradermal administration of BCG vaccine via the Bioject ID Pen.
干预措施: Bioject ID Pen (Device)
Needle and syringe
Intradermal administration of BCG vaccine via needle and syringe.
干预措施: Needle and syringe (Device)
结局指标
主要结局
Systemic Adverse Events
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
未报告次要终点