Human Challenge With Live-attenuated Rotavirus to Assess Next-generation Rotavirus Vaccines in Africa
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 720
- 试验地点
- 1
- 主要终点
- Vaccine Shedding
研究概览
简要总结
Despite the widespread introduction of vaccines against Rotavirus, Rotavirus continues to be a cause of significant morbidity and mortality in the developing world. This study will assess protection against rotavirus infection and investigate immune correlates of protection following vaccination with a novel trivalent VP8 subunit rotavirus vaccine used alone or in combination with oral rotavirus vaccine.
详细描述
This is a randomized, open-label clinical trial of Rotarix and trivalent VP8 subunit vaccine given alone or in combined schedules to 720 infants in Zambia at 6, 10 and 14 weeks followed by challenge at 18 weeks used to assess mucosal immunity.
Potential participants will be identified through antenatal and child health monitoring clinics in selected facilities in Lusaka Zambia. Interested parents will be invited to the clinical research site for informed consent procedures and assessment of eligibility. Children meeting the eligibility criteria with written informed consent for participation will be randomized to one of the four available study arms using simple randomization in block sizes of 8. Blood, stool, and saliva samples will be collected prior to completing vaccination according to randomization arm. All parents/guardians will be provided with post immunisation diary cards to document any reactions following vaccination. Trained study staff will contact parents and guardians of enrolled participants weekly to enquire on the child's health and assist with documentation of solicited reactions following vaccinations.
Enrolled children will be followed up for at least five months following enrollment. Follow up vaccinations will be provided each month until all children have completed all assigned study vaccinations. Upon completion of study vaccination, participants will be challenged with oral rotavirus vaccine, Rotarix TM to assess mucosal immunity.
Primary outcome:
The primary objective of the study will be to detect a reduction in the proportion of children shedding vaccine rotavirus in stool at any timepoint 5-9 days after challenge, among children immunized with P2-VP8 subunit vaccine alone or in combination with Rotarix, compared with infants receiving Rotarix alone. The primary outcomes will be prevalence of rotavirus (Rotarix) shedding at any timepoint in samples collected 5,7 and 9 days after challenge.
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
- None
入排标准
- 年龄范围
- 6 Weeks 至 10 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy infants as established by medical history and physical examination.
- •Infants will be 6-10 weeks old at time of enrollment
- •parents plan to remain in the area for the duration of the study.
- •Parent/guardian understands the study procedures and willing to provide informed consent to participate in the study
排除标准
- •Acutely unwell
- •Infant or infant's mother has syndromic or documented evidence of being immunocompromised (independent of HIV status)
- •Known allergy to any vaccine component
- •Previously received rotavirus vaccine
- •Received immunosuppressive medication
- •Major congenital or genetic abnormality
- •Any 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.
- •Participant's parents not available or willing to accept active follow-up by the study staff
研究组 & 干预措施
P2 VP8 only
Parenteral P2-VP8 subunit vaccine will be administered at 6, 10 and 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 & 9 days later.
干预措施: Trivalent P2-VP8 (Biological)
Rotarix + 1 dose P2-VP8
Rotarix will be administered at 6 and 10 weeks of age, followed by parenteral P2-VP8 subunit vaccine at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 & 9 days later.
干预措施: Rotarix (Biological)
Rotarix + 1 dose P2-VP8
Rotarix will be administered at 6 and 10 weeks of age, followed by parenteral P2-VP8 subunit vaccine at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 & 9 days later.
干预措施: Trivalent P2-VP8 (Biological)
Rotarix + 3 doses P2-VP8
Rotarix and parenteral P2-VP8 subunit vaccine will be coadministered at 6 and 10 weeks of age, with an additional dose of P2-VP8 subunit vaccine administered at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 & 9 days later.
干预措施: Rotarix (Biological)
Rotarix + 3 doses P2-VP8
Rotarix and parenteral P2-VP8 subunit vaccine will be coadministered at 6 and 10 weeks of age, with an additional dose of P2-VP8 subunit vaccine administered at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 & 9 days later.
干预措施: Trivalent P2-VP8 (Biological)
结局指标
主要结局
Vaccine Shedding
时间窗: 5-9 days after Challenge
to detect a reduction in the proportion of children shedding vaccine rotavirus in stool at any timepoint 5 -9 days after challenge, among children immunized with P2-VP8 subunit vaccine alone or in combination with Rotarix, compared with infants receiving Rotarix alone. We estimate that approximately 50% (range 30-70%) of children previously vaccinated with 2 doses of Rotarix will shed Rotarix detected by Polymerase Chain Reaction (PCR) at any timepoint 5-9 days after challenge
次要结局
- Seroconversion following vaccination(14 and 18 weeks of age)
- Immune boosting(7 days after 3rd clinic visit)