Age-descending, Randomized, Placebo-controlled Phase 2 Trial in Three Sites in Sub-Saharan Africa to Assess the Safety and Immunogenicity of a Parenteral Trivalent Salmonella (S. Enteritidis/S. Typhimurium/S. Typhi Vi) Conjugate Vaccine (TSCV) Versus Placebo
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 800
- 试验地点
- 2
- 主要终点
- Safety and reactogenicity of Full-strength and Half-strength TSCV
研究概览
简要总结
This is an age-descending, randomized, placebo-controlled trial that will evaluate the safety and immunogenicity of a Trivalent Salmonella conjugate vaccine (TSCV). The trial will proceed from adults, to children, to toddlers, and then to infants.
详细描述
This is an age-descending, randomized, placebo-controlled trial that will evaluate the safety and immunogenicity of a Trivalent Salmonella conjugate vaccine (TSCV). The trial will proceed from adults, to children, to toddlers, and then to infants.
In Step 1A-D of the trial, participants will be randomized to receive a single dose of TSCV (Full-strength or Half-strength), Typbar-TCV, or placebo, first in adults, then in children 5 to 9 years of age, then children 24 to 59 months of age, and then 16 to 23 months of age.
Participants will be followed for 6 months. After a Data Safety Monitoring Board (DSMB) review of the safety data, the trial will proceed to Step 2A and 2B whereupon 12- to 16-month-old toddlers and infants 8- to 11-months of age will be similarly and simultaneously randomized. Participants will be followed for 6 months.
After another DSMB safety review, Step 3 will commence with simultaneous enrollment of 12- to 14-week-old and 16- to 18-week-old infants who will each receive a single dose of TSCV, TCV or placebo. Participants will be followed for 6 months.
After a third DSMB safety review and selection of the preferred TSCV formulation (Full-strength versus Half-strength) for further clinical development (a decision taken by the Sponsor, Manufacturer, and funder, while taking into consideration the recommendation of the DSMB), Step 4 will evaluate a two-dose regimen. Infants 12 to 18 weeks of age will be randomized to receive either two doses of TSCV (at Full-strength or Half-strength, based on results from Steps 1-3) or placebo followed by Typbar-TCV. The priming dose will be administered at enrollment and the booster at ~9, ~12, or ~15-17 months of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Weeks 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy individuals, female or male
- •Age (all age ranges are inclusive)
- •Step 1A: Adults 20-35 years of age
- •Step 1B: Children, 5-9 years of age
- •Step 1 C: Pre-school children, 24-59 mos. of age
- •Step 1D: Older toddlers, 16-23 months of age
- •Step 2A: Young toddlers, 12-16 months of age
- •Step 2B: Older infants, 8-11 months of age
- •Step 3: Young infants,12-14 weeks of age OR 16-18 weeks of age
- •Step 4: Young infants, 12-18 weeks of age
- •For potential pediatric participants, the parents must live within the catchment area of the clinical study facility at the time of the study vaccinations and must intend to continue to reside in the area for the duration of the study
- •Adult subjects and parents/ guardians of pediatric subjects must have provided informed consent
- •Infant and toddler subjects in Steps 2, 3, and 4 must have received their scheduled EPI vaccines at least 14 days prior to receiving a study product.
排除标准
- •A history of documented hypersensitivity to any component of the Trivalent Salmonella Conjugate Vaccine or of Typbar-TCV™
- •A history of previous vaccination with any licensed or experimental typhoid vaccine A known history of diabetes, tuberculosis, malignancy, chronic kidney disease, cardiac disease, liver disease, progressive neurological disorder, poorly controlled seizure disorder, or a terminal illness based on participant interview and review of screening laboratory results.
- •Severe malnutrition: i.e., weight-for-length Z-score of less than -
- •Receipt of any other investigational intervention in the last 6 months
- •Known HIV infection or other forms of immunocompromise
- •Receipt of systemic immunosuppressive medication including systemic corticosteroids
- •For Step 1A, for females of child-bearing potential, a positive pregnancy test at the time of enrollment.
- •For Step 1B, any female child who has experienced menarche.
- •Acute illness with or without fever (temperature >38.0oC) is a temporary exclusion criterion. Enrollment may be postponed until 3 days after the illness has resolved.
- •Positive malaria test is a temporary exclusion criterion. Participant may be enrolled 3 days after completing treatment.
- •Any condition determined by the investigators to be likely to interfere with evaluation of the vaccine, to be a significant health risk to the participant, or to make it unlikely that the participant would complete the study
研究组 & 干预措施
TSCV (Half-strength)
Half-strength GMP formulation of TSCV
干预措施: TSCV (Half-strength) (Drug)
TSCV (Full-strength)
Full-strength GMP formulation of Trivalent Salmonella Conjugate Vaccine (TSCV)
干预措施: TSCV (Full-strength) (Drug)
Typbar-TCV
Licensed Monovalent Typbar-TCV
干预措施: Typbar-TCV (Drug)
Placebo
PBS
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and reactogenicity of Full-strength and Half-strength TSCV
时间窗: Through Day 366 of follow-up post vaccination
The proportion of participants who experience Serious Adverse Events through their participation in the study.
Safety and reactogenicity after primary dose of TSCV and after booster dose of TSCV or Typbar-TCV™ [At each booster age group (9, 12, or 15-17 mo. of age)]
时间窗: Until the end of the participant study period - 6 months to 1 year post vaccination
The proportion of participants who experience Serious Adverse Events through their participation in the study.
Non-inferiority analysis: immunogenicity of Full-strength vs. Half-strength TSCV
时间窗: Through day 29 post vaccination
Serum IgG anti-COPS antibodies (to both S. Enteritidis and S. Typhimurium antigens)
Immunogenicity of two-dose regimen of TSCV [At each booster age group (9, 12 or 15-17 months of age)]
时间窗: At day 29 post booster vaccination
The rates of seroconversion of serum IgG anti-COPS at each booster age group
Safety and reactogenicity of Full-strength and Half-strength TSCV
时间窗: first 30 minutes after parenteral immunization
The proportion of participants in each product group and within each age group who develop adverse events (AEs) in the first 30 minutes after parenteral immunization
Safety and reactogenicity of Full-strength and Half-strength TSCV
时间窗: over 7 days post-vaccination.
The proportion of participants in each product group and within each age group who develop adverse events (AEs) in the 7 days post-vaccination.
Safety and reactogenicity of Full-strength and Half-strength TSCV
时间窗: through Day 29 of follow-up post-vaccination
The proportion of participants who experience AEs through Day 29 of follow-up post-vaccination.
Safety and reactogenicity after primary dose of TSCV and after booster dose of TSCV or Typbar-TCV™ [At each booster age group (9, 12, or 15-17 mo. of age)]
时间窗: over 7 days post-vaccination.
The proportion of participants in each product group who develop adverse events (AEs) in 7 days post-vaccination.
Safety and reactogenicity after primary dose of TSCV and after booster dose of TSCV or Typbar-TCV™ [At each booster age group (9, 12, or 15-17 mo. of age)]
时间窗: through Day 29 of follow-up after each vaccination.
The proportion of participants who experience AEs through Day 29 of follow-up after each vaccination.
次要结局
未报告次要终点
研究者
Milagritos Tapia
Professor
University of Maryland, Baltimore