A Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of Novel Oral Polio Type 2 Vaccine Candidate in Healthy Newborns in Bangladesh
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 330
- 试验地点
- 2
- 主要终点
- Safety of nOPV2 vaccine
研究概览
简要总结
Though OPV is safe and effective, it can mutate and reacquire neurovirulence in rare circumstances. This can result in vaccine-associated paralytic polio and circulating vaccine-derived polioviruses. Use of tOPV had risk of generating VAPP and seeding new type 2 circulating vaccine-derived polioviruses though wild type 2 virus was eradicated in September 2015. For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to bOPV. cVDPV2 outbreaks have occurred in sixteen countries after cassation of OPV2. Using stockpiled mOPV2 to respond to this situation risks propagating new cVDPVs. IPV induces only limited intestinal mucosal immunity not effective to interrupt fecal-oral route transmission in settings of poor hygiene and sanitation. Therefore, development of novel oral polio vaccine with enhanced genetic stability and lower risk of reversion to neurovirulence compared to current Sabin 2 strains is major priority of global polio eradication Program
Current clinical development plan outlines studies through Phase II development with nOPV2 candidate strains being tested in adult toddler and infant populations who received prior dose of OPV or IPV. No study has been conducted in truly naive newborns with no prior receipt of any polio vaccines
Hypothesis: Vaccinating healthy newborns with novel type 2 polio virus candidate vaccines is safe and can induce putatively protective immune response
Objectives
Primary Objective
Safety
To evaluate the safety and tolerability after one and two doses of nOPV2 vaccine candidates 1 given 4 weeks apart in poliovirus vaccine-naïve newborn Immunogenicity To evaluate the immune response to vaccination after one and two doses of nOPV2 vaccine candidate 1 given 4 weeks apart in poliovirus vaccine-naïve newborns
Secondary objectives
Immunogenicity
To evaluate seroprotection rate geometric mean and median titers to vaccination after one dose of nOPV2 vaccine candidate 1 in poliovirus vaccine-naïve newborns To further evaluate seroprotection rate geometric mean and median titers to vaccination after two doses of nOPV2 candidate 1 in poliovirus vaccine-naïve newborns
Viral Shedding
To assess trate of fecal viral shedding at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns To assess duration of fecal viral shedding at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns To assess extent of fecal viral at fixed time points following one and two doses of nOPV2 vaccine candidate 1 in newborns
Exploratory objective
To assess genetic stability through genetic deep sequencing assay and neurovirulence test through transgenic mice NV assays from a subset of participants stools samples
详细描述
Burden: Oral Polio Vaccine (OPV) contains attenuated (weakened) polioviruses. Though OPV is safe and effective, it can mutate and reacquire neurovirulence in rare circumstances. This can result in vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived polioviruses (cVDPVs) on rare occasions. Use of tOPV, therefore, had the risk of generating VAPP and seeding new type 2 circulating vaccine-derived polioviruses (cVDPV2), even though the wild type 2 virus was eradicated in September 2015. For this reason tOPV vaccine was withdrawn globally in April 2016 and switched to the bivalent oral poliovirus vaccine (bOPV). Circulating vaccine-derived type-2 poliovirus (cVDPV2) outbreaks have occurred in sixteen countries after cassation of OPV2. Using stockpiled mOPV2 to respond to this situation risks propagating new cVDPVs and this phenomenon has already been observed in multiple geographies following the switch. Inactivated polio vaccine (IPV) induces only limited intestinal mucosal immunity and is not effective to interrupt fecal-oral route transmission in settings of poor hygiene and sanitation. Therefore, development of novel oral polio vaccine/s with enhanced genetic stability and lower risk of reversion to neurovirulence compared to current Sabin 2 strains is a major priority of the global polio eradication Program.
Knowledge gap: The current clinical development plan outlines studies through Phase II development with the nOPV2 candidate strains being tested in adult, toddler, and infant populations who have received prior dose/s of OPV and/or IPV. No study has been conducted in truly naive newborns with no prior receipt of any polio vaccines to strengthen the clinical evidence in favour of utilizing these novel OPV strains.
Relevance: Existing Sabin type 2 polio virus vaccines can mutate in to pathogenic virus and become neurovirulent, causing VAPP and cVDVP. So novel type 2 polio virus candidate vaccines is an urgent need especially for outbreak situations. The nOPV2 strains are intended for use as safer alternatives to mOPV2 vaccines for outbreak response. Data from this proposed study result will further strengthen the clinical evidence base to deploy novel, genetically stable OPV strains to reduce the risk of generating cVDPV and VAPP. The study will generate data on novel OPV2 candidates for pre-licensure use in outbreak scenarios and for eventual full licensure and WHO Prequalification.
Hypothesis : Vaccinating healthy newborns with novel type 2 polio virus candidate vaccines (nOPV2) is safe and can induce a putatively protective immune response.
Objectives:
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 Hour 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Newborns at birth (range: 0-3 days of age).
- •Mothers that consent for participation in the full length of the study.
- •Mothers those are able to understand and comply with planned study procedures.
排除标准
- •Mother and newborns who are unable to participate in the full length of the study.
- •A diagnosis or suspicion of immunodeficiency disorder either in the newborn or in an immediate family member.
- •A diagnosis or suspicion of bleeding disorder that would contraindicate collection of blood by venipuncture.
- •Acute diarrhea, infection or illness at the time of enrollment that would require admission to a hospital.
- •Acute vomiting and intolerance to liquids within 24 hours before the enrollment visit.
- •Receipt of any polio vaccine (OPV or IPV) and Rotavirus Vaccine (RVV) before enrollment based upon documentation or mothers recall.
- •Newborns from multiple births. Newborns from multiple births will be excluded to reduce the potential for contact transmission of vaccine poliovirus to siblings. The newborn from a multiple birth who is /are not enrolled would be likely to receive routine immunization and transmit vaccine poliovirus to the enrolled infant.
- •Newborns from premature births (<37 weeks of gestation).
结局指标
主要结局
Safety of nOPV2 vaccine
时间窗: Upto 3 months
* Incidence rate of solicited systemic AEs within 7 days after each dose of vaccine * Incidence rate of unsolicited AEs during entire study period * Incidence rate of serious AEs and AESIs during entire study period
Immunogenecity of nOPV2 vaccine , will be assessed as poliovirus type-2-specific serum neutralising antibodies
时间窗: 4 weeks
Proportion of participants showing seroconversion and seroprotection will be calculated and reported
Viral shedding in participants stool will be measured and reported by proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools
时间窗: 12 weeks
Vaccine poliovirus shedding in the study participants stool will be assessed by real-time RT-PCR method.
次要结局
- Genetic assay and Neurovirulance test to assess genetic stability by demonstrating the retention of key genetic regions engineered in the vaccine candidate(4 weeks)