A Randomized, Double-blind, Dose-escalation Clinical Trial of the Safety, Reactogenicity and Immunogenicity of MTBVAC Compared to BCG Vaccine SSI, in Newborns Living in a Tuberculosis Endemic Region With a Safety Arm in Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Safety and reactogenicity in infants and adults: includes injection site and systemic and regional adverse events, solicited and unsolicited. A diary card will be for solicited local, regional, and systemic adverse event data.
研究概览
简要总结
Randomized, controlled, double blind clinical trial in 2 stages (adult stage, infant stage). The first stage includes 18 HIV uninfected, QFT negative, BCG vaccinated, adult participants, randomized 1:1 to receive BCG Vaccine SSI or MTBVAC at equivalent dose (5x10E05 CFU/0.1mL) (n=9 in each group). Upon favourable safety review by the DSMB for all 18 adults up to day 28 after study vaccination, the second stage will commence in thirty-six (36) HIV unexposed, BCG naïve, newborn infants, randomized 1:3 to receive BCG Vaccine SSI or MTBVAC at one of three different dose levels ( (n=9 in each group).
详细描述
Adult Stage:
Eighteen (18) adult participants will be recruited and randomized equally into 1 of 2 study groups (n=9 per group): MTBVAC highest dose group (approx. 5x10E05 CFU/0.1mL) or BCG SSI standard human dose (approx. 5x10E05 CFU/0.1mL).
Safety assessments will be conducted at D0, D7, D14, D28, D56, D90, and D180 post study vaccination. A diary card will be used to collect solicited local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data will be collected at each study visit. Non-serious adverse events will be collected through D28. Serious adverse events will be collected during the entire study period.
Infant Stage:
Thirty-six (36) infant participants will be recruited, randomized and allocated into 4 groups of 9 participants: BCG (single dose level 2.5 x 10E05 CFU/0.05 mL); or MTBVAC at three different dose levels (lowest 2.5x10E03 CFU/0.05mL, middle 2.5x10E04 CFU/0.05mL, highest 2.5x10E05 CFU/0.05mL).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 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, or PCR) negative
- •Quantiferon®-TB Gold (Cellestis) test for latent TB infection negative within 3 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, not lactating, and willingness to use an acceptable method of contraception to avoid pregnancy for the duration of the study
- •Infant Stage:
- •Inclusion Criteria:
- •Male or female neonates within 96 hours of birth.
- •Written informed parental 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 antenatal history, delivery records, 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.
- •Estimated gestational age more than or equal to 38 weeks
排除标准
- •Adult stage Exclusion criteria
- •A history or evidence of an acute or chronic medical or surgical condition likely to affect the safety, reactogenicity, or immunogenicity of the investigational vaccine
- •Skin condition, bruising or birth mark at the intended injection site.
- •History or evidence of previous or current active TB disease
- •History of a household contact with active TB disease who has received less than 2 months treatment
- •Infant Stage Exclusion criteria:
- •Infant must not have received routine BCG vaccination prior to enrolment.
- •Antenatal, intrapartum, or postnatal medical or surgical condition that may affect the safety, reactogenicity, or immunogenicity of the investigational vaccine.
- •Maternal HIV test (rapid test, ELISA or PCR) not performed antenatally, HIV test results not available, or HIV test result known positive.
- •Maternal or other household contact with newly diagnosed or incompletely treated active TB disease.
研究组 & 干预措施
BCG Control Group
Intervention: commercially available BCG live vaccine
干预措施: BCG (Biological)
MTBVAC Group 2
Intervention: MTBVAC live vaccine (middle dose)
干预措施: MTBVAC (Biological)
MTBVAC Group 1
Intervention: MTBVAC live vaccine (low dose)
干预措施: MTBVAC (Biological)
MTBVAC Group 3
Intervention: MTBVAC live vaccine (high dose)
干预措施: MTBVAC (Biological)
结局指标
主要结局
Safety and reactogenicity in infants and adults: includes injection site and systemic and regional adverse events, solicited and unsolicited. A diary card will be for solicited local, regional, and systemic adverse event data.
时间窗: Six (6) months post-study vaccination
次要结局
- Primary immunogenicity analysis (in infants only): Measure of frequencies and co-expression patterns of CD4 and CD8 T cells expressing specific cytokines in whole blood.(Six (6) months post-study vaccination)