A Phase III, Double-blind, Randomized, Placebo Controlled Study to Evaluate the Mucosal Intestinal Immunity to Poliovirus Type-2 of nOPV2 at Birth Dose in Healthy IPV Vaccinated Infants
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 740
- 试验地点
- 2
- 主要终点
- Stool viral load
研究概览
简要总结
The study will compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks of age).
详细描述
To meet the urgent public health need regarding cVDPV2 outbreaks, a novel type 2 OPV (nOPV2) vaccine was developed using attenuated serotype 2 polioviruses derived from a modified Sabin 2 infectious cDNA clone generated by modifying the Sabin-2 ribonucleic acid (RNA) sequence to improve genetic stability and make the strains less prone to reversion to virulence. Clinical trials in adults, children, and infants demonstrated that nOPV2 vaccine is safe, well tolerated, and immunogenic. These include a phase 2 study of vaccine-naïve neonates in Bangladesh who received either two doses of nOPV2 or two doses of placebo at birth and 4 weeks of age concluded that the vaccine was well tolerated and immunogenic, as 90% of the infants seroconverted at 2 weeks post second dose. Overall 99% of infants had protective levels of neutralizing antibody at this time in contrast to the seroprotection rate of 56% in the placebo group.
Although immunogenic, the effect of nOPV2 on virus transmission is still unclear. This phase 3 study aims to compare the transmissible levels of poliovirus type-2 detected in stool samples collected at the time of the nOPV2 challenge (pre-challenge) and subsequent timepoints in 3 groups of newborns receiving an nOPV2 dose at birth and primed with 3 doses of IPV (6 - 10 - 14 weeks 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
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 7 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Newborn infants of maximum 1 week of age with birth weight > 2,500 g.
- •Healthy infants without obvious medical conditions like immunodeficiency diseases, severe congenital malformations, severe neurological diseases or any other disease that require high doses of corticosteroids or immunotherapies that preclude the subject from participating in the study as established by medical history and physical examination.
- •Written informed consent obtained from both parents or legal guardian(s) as per country regulations.
- •Resides in the area and parents willing to adhere to all study procedures.
排除标准
- •Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus infection in the potential participant or any member of the participant's household.
- •Household member who has receive any novel OPV 1 month before birth of this study's participant up through 1 month post-last-dose.
- •Family history of congenital or hereditary immunodeficiency.
- •Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
- •Known allergy to any component of the study vaccines or to any antibiotics that share molecular composition with a component of the study vaccines.
- •Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV)
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- •Acute severe febrile illness (≥37.5 °C) on the day of vaccination deemed by the Investigator to be a contraindication for vaccination (the child can be included at a later time if within age window and all inclusion criteria are met.).
- •Participant 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 participant.
- •Infants from multiple births or born prematurely (< 37 weeks of gestation).
研究组 & 干预措施
Placebo
Approximately 330 subjects to receive 2 doses of placebo at birth and 14 wks of age plus a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age
干预措施: nOPV2 (Biological)
nOPV2 at birth
Approximately 330 subjects to receive 1 dose of nOPV2 at birth followed by a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age.
干预措施: nOPV2 (Biological)
nOPV2 at birth and Wk 14 of age
Approximately 80 subjects to receive 2 doses of nOPV2 at birth and 14 wks of age plus a regular IPV schedule at approx. 6, 10, 14 weeks of age and an nOPV2-002 challenge at approx. 18 weeks of age.
干预措施: nOPV2 (Biological)
结局指标
主要结局
Stool viral load
时间窗: From enrollment to the end of the study at Wk 22 of age.
To assess the presence or absence of "transmissible" levels of virus in stool, with presence defined as a log10 CCID50 per gram of ≥4.3 at Visit 7 (Day 126; day of nOPV2 challenge dose administration), Visit 8 (Day 130), Visit 9 (Day 133), Visit 10 (Day 140), and Visit 11 (Day 154) in all groups.
次要结局
- PV Type 2 neutralizing activity in stool samples(From enrollment to the end of the study at 22 Wks of age.)
- PV Type 2 seroprotection rate(From enrollment till 18 Wks of age)
- PV Type 2 seroconversion rate(From enrollment till Wk 18 of age.)
- PV Type 2 neutralization titers(From enrollment till Wk 18 of age)
- SAEs and IMEs(From enrollment to the end of the study at Wk 22 of age)
- Solicited AEs(From enrollment to Wk 18 of age)
- Viral shedding(From enrollment to the end of the study at Wk 22 of age.)