A Phase 4, Randomized, Open-Label Study to Assess Humoral and Intestinal Polio Immunity Following a Three-Dose Trivalent Inactivated Polio Vaccine Schedule Relative to Two Sequential Schedules of IPV/Bivalent Oral Polio Vaccines
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 570
- 试验地点
- 2
- 主要终点
- Types 1 and 3 poliovirus humoral immune response
研究概览
简要总结
The rationale for this study (IPV 002ABMG) is to evaluate and compare three doses of IPV, two doses of IPV plus one bOPV, and one dose of IPV plus two doses of bOPV in order to provide evidence for better immunization policy making in regions of the world that must switch to use of IPV/bOPV schedules in the 2014-2015 time frame. The goal is to identify the best option optimizing humoral immune responses, intestinal immunity and thereby prevent community transmission as well as preventing VAPP. Specifically, the study seeks to show that both of the sequential regimens are equivalent (not-inferior) to the 3-dose IPV regimen in the seroconversion rates to both type 1 and type 3 poliovirus such that not more than 10% of subjects fall below the 95% confidence interval observed for the 3-dose IPV alone regimen and the geometric mean titers (GMTs) are no more than 2/3 logs less than those for the 3-dose IPV regimen. In addition, the study will evaluate by a novel method (poliovirus shedding index), the adequacy of IPV vaccines in inducing intestinal immunity, specifically by reducing the shedding of poliovirus type 2 after an OPV challenge. The hypotheses of the study are:
- A 3-dose IPV/bOPV sequential schedule including 1 or 2 doses of bOPV is non-inferior in terms of types 1 and 3 seroconversion rates and GMTs to a 3-dose IPV schedule.
- Two and possibly 1 IPV dose(s) provides significant seroconversion rates and GMTs to type 2 poliovirus and sufficient priming to induce a rapid immune response in the context of an oral challenge at 7 months of age.
- Three, 2, and possibly 1 dose of IPV will induce intestinal immunity to poliovirus type 2 as measured by a combination of quantity of virus in stools and duration of shedding (shedding index).
In addition to these 3 hypotheses, the study will explore the following hypothesis:
• Co-administration of bOPV and rotavirus at 16 weeks of age (the second rotavirus dose) provides similar antirotavirus IgA seroconversion rates and GMCs compared to subjects receiving rotavirus vaccine together with IPV.
详细描述
3.0 STUDY DESIGN This is a multicenter, randomized, unblinded study. Healthy infants attending the well-child care at outpatient clinics and due for their first dose of polio vaccines will be eligible for the study. Infants 8 wks ± 7 days of age will be randomized and allocated to three treatment groups.
4.0 STUDY POPULATION The study will be conducted in up to 7 "vacunatorios" in Chile. Parents or legal guardians of healthy infants, who are receiving well-child care at designated outpatient clinics, will be approached to participate in the study.
5.0 TREATMENT OF SUBJECTS 5.1 Vaccines The vaccines to be used in this study include bOPV, mOPV2, and IPV (see Section 14.2 for package inserts).
5.1.1 Bivalent Oral Polio Vaccine (bOPV) Produced by Sanofi Pasteur, Lyon, France, bivalent OPV vaccine contains types 1 and 3 polioviruses and it is indicated for supplementary immunization activities in children from 0 to 5 years of age to prevent or contain outbreaks caused by these 2 serotypes. The vaccine contains at least 6.0 log CCID50 of LS c2ab live attenuated polio virus type 1; and at least 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. The vaccine dose is 2 drops (0.1 mL) using a multi-dose dropper vial, given directly into the mouth. The vaccine should be stored in a freezer at -20°C, and after thawing it can be stored up to 6 months at refrigerated temperatures of +2 to +8°C.
5.1.2 Monovalent Oral Polio Vaccine Type 2 (mOPV2) Monovalent OPV type 2 live attenuated poliomyelitis virus vaccine (mOPV2) is produced by Glaxo SmithKline, Rixensart, Belgium, as a sterile suspension of poliovirus serotype 2 for oral administration. Each dose (0.1 mL) contains not less than 105.0 CCID50 of the Sabin strain type 2 (P 712, Ch, 2ab). This will be the challenge OPV strain used to assess intestinal shedding and immunity. The vaccine should be stored in a freezer at -20°C, and after thawing it can be stored up to 6 months at refrigerated temperatures of +2 to +8°C.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 7 Weeks 至 9 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 8 weeks (-7 to +7 days).
- •Healthy infants of all ethnicities and both genders without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination.
- •Written informed consent obtained from 1 parent or legal guardian who, in the opinion of the investigator, is capable of understanding and complying with the protocol requirements.
排除标准
- •Previous vaccination against poliovirus.
- •Low birth weight (BW <2,500 grams).
- •Twins or multiple pregnancy infants.
- •Another family or household member who has received OPV within the past 6 months or is going to receive OPV within the following 6 months.
- •Any confirmed or suspected immunosuppressive or immunedeficient condition including human immunodeficiency virus (HIV) infection.
- •Family history of congenital or hereditary immunodeficiency.
- •Major congenital defects or serious chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
- •Known allergy to any component of the study vaccines.
- •Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- •Subject who, in the opinion of the Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject.
结局指标
主要结局
Types 1 and 3 poliovirus humoral immune response
时间窗: 12 months
Two primary endpoints will be used as the basis for evaluation of the IPV/OPVb sequential regimens compared to three doses of IPV: * Seroconversion to type 1 (type-specific titers ≥1:8 and \> 4-fold over expected levels of maternally-derived antibody) and GMTs achieved at 28 weeks. * Seroconversion to type 3 (type-specific titers ≥1:8 and \> 4-fold over expected levels of maternally-derived antibody) and GMTs achieved at 28 weeks.
次要结局
- Poliovirus Type 2 humoral and intestinal immune response and safety(12 months (18 months for intestinal immunity))
研究者
Miguel O'Ryan Gallardo
Full Professor and Associate Director for Innovation, Faculty of Medicine, University of Chile
University of Chile