Phase I/II Descending Age Double-blinded Randomized Placebo-controlled Dose Escalation Study to Examine the Safety Reactogenicity Tolerability & Immunogenicity of the P2-VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers & Infants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 204
- 试验地点
- 2
- 主要终点
- Number of Participants With Vaccine Induced Reactions
研究概览
简要总结
This is is a study of a parenteral rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study will examine the safety and immunogenicity of this vaccine first in healthy South African toddlers. If the safety profile is deemed appropriate, the study will continue to explore the safety and immunogenicity of the vaccine in healthy South African infants.
The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated in healthy toddlers and infants. The primary immunogenicity hypothesis is that the P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response in at least 80% of participants in at least one of the study groups.
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
- 6 Weeks 至 35 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy infants/toddlers as established by medical history and clinical examination before entering study
- •toddler cohort: > or = 2 and <3 years old at the time of enrollment
- •infant cohort: > or = 6 and <8 weeks at the time of enrollment
- •parental ability and willingness to provide informed consent
- •parental intention to remain in the area with the child during the study period.
排除标准
- •Presence of fever on the day of enrollment
- •Acute disease at the time of enrollment
- •Concurrent participation in another clinical trial throughout the entire timeframe for this study
- •Presence of malnutrition or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol
- •For infant cohort, history of premature birth (<37 weeks gestation)
- •History of congenital abdominal disorders, intussusception, or abdominal surgery
- •Known or suspected impairment of immunological function based on medical history and physical examination
- •For infant cohort only, prior receipt of rotavirus vaccine
- •A known sensitivity or allergy to any components of the study vaccine
- •History of anaphylactic reaction
- •Major congenital or genetic defect
- •Participant's parents not able, available or willing to accept active weekly follow-up by the study staff
- •Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period
- •History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study
- •Any medical condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent
- •HIV infection
- •For toddlers, to be assessed by HIV ELISA
- •For infants, to be assessed by PCR, if mother is not known to be negative (negative test result between 24 weeks gestation and screening)
研究组 & 干预措施
Cohort A P2-VP8 30 mcg
Cohort A toddlers (24-35 mo) receiving P2-VP8 Subunit Vaccine (30 mcg)
干预措施: P2-VP8 Subunit Vaccine 30 mcg (Biological)
Cohort A Placebo
Cohort A toddlers (24-35 mo)
干预措施: Placebo (Other)
Cohort A P2-VP8 60 mcg
Cohort A toddlers (24-35 mo) receiving high dose P2-VP8 Subunit Vaccine (60mcg)
干预措施: P2-VP8 Subunit Vaccine 60mcg (Biological)
Cohort B P2-VP8 10mcg
Cohort B infants receiving P2-VP8 Subunit Vaccine (10mcg)
干预措施: P2-VP8 Subunit Vaccine 10mcg (Biological)
Cohort B placebo
Cohort B infants aged 6 to < 8 weeks receiving placebo
干预措施: Placebo (Other)
Cohort B P2-VP8 30mcg
Cohort B infants aged 6 to < 8 weeks receiving P2-VP8 Subunit Vaccine (30mcg)
干预措施: P2-VP8 Subunit Vaccine 30 mcg (Biological)
Cohort B1 P2-VP8 60mcg
Cohort B1 Infants aged 6 to < 8 weeks receiving P2-VP8 Subunit Vaccine (60mcg)
干预措施: P2-VP8 Subunit Vaccine 60mcg (Biological)
Cohort A P2-VP8 10mcg
Cohort A toddlers (24-35 mo) receiving P2VP8 Subunit Vaccine (10mcg)
干预措施: P2-VP8 Subunit Vaccine 10mcg (Biological)
结局指标
主要结局
Number of Participants With Vaccine Induced Reactions
时间窗: 7 days following each dose
Maximum severity of all local reactions or systemic reactogenicity after any vaccination
Number of Participants With Serious Adverse Events
时间窗: within 28 days of a study dose and at any time
Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study
Number of Participants Reporting Any Non-Serious Adverse Event
时间窗: 6 mo following first vaccination
all adverse events will be recorded over the duration of the 6 month follow up period.
Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse.
时间窗: Baseline to day 84
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages.
Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses
时间窗: Baseline to day 84
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.
Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8])
时间窗: Baseline to Day 84
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.
次要结局
- Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo.(Rotarix vaccination on Day 84 to day 91)