A Phase 1/2, Randomized, Observer-Blind, Active-Controlled, Age De-escalation, Dose Combination Ranging Study to Assess the Safety and Immunogenicity of Co-administered Novel Live Attenuated Trivalent Oral Poliomyelitis Vaccine in Healthy Adults, Young Children, and Neonates and Co-administered Novel Live Attenuated Monovalent Oral Poliomyelitis Vaccines 1 and 2 in Neonates in Bangladesh
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 2,400
- 试验地点
- 1
- 主要终点
- Number of Participants with Serious Adverse Events (SAEs)
研究概览
简要总结
The main objectives of this study are to :
- evaluate the safety and tolerability of trivalent novel oral poliovirus vaccines (tnOPV) in healthy adults, young children, and neonates, relative to those receiving control vaccines;
- evaluate the safety and tolerability of combined novel oral poliovirus vaccine type 1 (nOPV1) + novel oral poliovirus vaccine type 2 (nOPV2) in neonates, relative to those receiving the bivalent (types 1 and 3) oral poliovirus vaccine (bOPV) control.
- compare type-specific cumulative seroconversion rates of poliovirus neutralizing antibody (NAb) titers, among all tnOPV dose combinations, following 4 vaccinations in healthy neonates;
- evaluate the type-specific cumulative seroconversion rate of poliovirus NAb titers among healthy neonates following 4 doses of combined nOPV1+nOPV2.
详细描述
This trial will use co-administered novel monovalent types 1, 2, and 3 vaccines to simulate administration of a potential trivalent vaccine and compare to the active control bOPV (bivalent Sabin types 1 and 3) and will be conducted at a single clinical center.
The study population will include healthy adults (≥18 to ≤45 years old) who have previously completed their full routine polio immunization series, healthy young children (≥1 to <5 years old) who have completed their full routine polio immunization series and healthy neonates (day of birth+3 days), who have not received any polio vaccination.
Enrollment in this study will be staggered into two stages and three age-descending cohorts.
Stage 1 will consist of an age-descension/dose escalation approach from adults to young children (Cohorts 1 and 2). Enrollment will begin with Cohort 1, in which 100 adults will be randomly allocated in a 1:1 ratio to Groups 1 and 2. Following a Protocol Safety Review Team (PSRT) review of the study Day 8 safety data (i.e. safety data reported up to 7 days post-vaccination #1, collected at Visit 2) of the adults in Cohort 1, and the absence of any safety concerns, 200 young children in Cohort 2 will be randomly allocated in a 1:1:1:1 ratio to Groups 3, 4, 5, and 6, respectively.
After the completion of enrollment of Cohort 2, the study will move into Stage 2. In addition to a PSRT review of Day 8 safety data of the young children in Cohort 2, there are two triggers of data from other studies to initiate the enrollment into Cohort 3:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 0 Days 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3
Adults will receive nOPV1 (10^6.5 Cell Culture Infectious Dose 50% [CCID₅₀]) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3
Adults will receive nOPV1 (10^6.5 Cell Culture Infectious Dose 50% [CCID₅₀]) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3
Adults will receive nOPV1 (10^6.5 Cell Culture Infectious Dose 50% [CCID₅₀]) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Adults:bOPV
Adults will receive bivalent OPV (types 1 and 3) on Day 1 and Day 29. Each dose (2 drops = 0.1 mL) contains >10^6.0 infective units of type 1 and >10^5.8 of type 3.
干预措施: Bivalent Oral Poliomyelitis Vaccine (bOPV) (Biological)
Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3
Children aged ≥ 1 to < 5 years old will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Young Children: Low-dose (LD) nOPV2
Children aged ≥ 1 to < 5 years old will receive nOPV2 (10^5.3 CCID₅₀) on Day 1 and Day 29.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Young Children: bOPV
Children aged ≥ 1 to < 5 years old will receive bivalent OPV (types 1 and 3) on Day 1 and Day 29. Each dose (2 drops = 0.1 mL) contains > 10^6.0 infective units of type 1 and > 10^5.8 of type 3.
干预措施: Bivalent Oral Poliomyelitis Vaccine (bOPV) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) plus nOPV3 (10^6.0 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3
Newborns will receive nOPV1 (10^6.5 CCID₅₀) plus nOPV2 (10^5.6 CCID₅₀) plus nOPV3 (10^6.5 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 3 (nOPV3) (Biological)
Neonates: bOPV
Newborns will receive bivalent OPV (types 1 and 3) at birth, week 6, week 10 and week 14 of life. Each dose (2 drops = 0.1 mL) contains >10^6.0 infective units of type 1 and >10^5.8 of type 3.
干预措施: Bivalent Oral Poliomyelitis Vaccine (bOPV) (Biological)
Neonates: MD nOPV1 + LD nOPV2
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 1 (nOPV1) (Biological)
Neonates: MD nOPV1 + LD nOPV2
Newborns will receive nOPV1 (10^6.0 CCID₅₀) plus nOPV2 (10^5.3 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
Neonates: LD nOPV2
Newborns will receive nOPV2 (10^5.3 CCID₅₀) at birth, week 6, week 10 and week 14 of life.
干预措施: Novel oral poliomyelitis vaccine type 2 (nOPV2) (Biological)
结局指标
主要结局
Number of Participants with Serious Adverse Events (SAEs)
时间窗: From the time of first study vaccination through the end of the study (197 days)
A serious adverse event is any adverse event that results in any of the following outcomes: 1. Death. 2. Is life-threatening. 3. Requires inpatient hospitalization or prolongation of existing hospitalization. 4. Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 5. Congenital abnormality or birth defect. 6. Important medical event that may not result in one of the above outcomes but may jeopardize the health of the study participant and require medical or surgical intervention to prevent one of the outcomes listed in the above definition of serious adverse event.
Number of Participants with Solicited Adverse Events (AEs) for 7 Days After Each Vaccination
时间窗: 7 days (day of vaccination and 6 following days) after each vaccination
Solicited AEs are pre-specified AEs that are common or known to be associated with vaccination that are actively monitored as potential indicators of vaccine reactogenicity.
Number of Participants with Unsolicited AEs for 28 Days After Each Vaccination.
时间窗: 28 days (day of vaccination and 27 following days) after each vaccination
Unsolicited AEs are any AEs reported spontaneously by the participant or parent, observed by the study personnel during study visits or identified during review of medical records or source documents.
Neonates: Seroconversion Rate of Types 1, 2, and 3 Anti-polio Serum Neutralizing Antibodies 28 Days After Last Vaccination
时间窗: Baseline and 28 days following the last vaccination (week 18)
For vaccine-naive neonates, seroconversion is defined as seropositive (titer ≥1:8) in those initially seronegative, or among those initially seropositive, as a minimum 4-fold higher (and seropositivity) than that which is expected due to maternal antibodies. This endpoint will be analyzed in neonates who receive nOPV types 1, 2, and 3.
Neonates: Seroconversion Rate of Types 1, 2, and 1 & 2 Combined Anti-polio Serum Neutralizing Antibodies 28 Days After Last Vaccination
时间窗: Baseline and 28 days following the last vaccination (week 18)
For vaccine-naive neonates, seroconversion is defined as seropositive (titer ≥1:8) in those initially seronegative, or among those initially seropositive, as a minimum 4-fold higher (and seropositivity) than that which is expected due to maternal antibodies. This endpoint will be analyzed in neonates who receive nOPV types 1 and 2 only.
次要结局
- Neonates: Type-specific and Multitypic Seroconversion Rate of Anti-polio Serum Neutralizing Antibodies(Baseline and weeks 6, 10, 14, and 18)
- All Cohorts: Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibody Titers Following Last Dose(Baseline and 4 weeks following the last vaccination (week 8 in adults and young children and week 18 in neonates))
- Neonates: Percentage of Participants Shedding Types 1, 2 and/or 3 Poliovirus Post-vaccination(From birth through 18 weeks)
- Adults and Young Children: Type-specific and Multitypic Seroconversion Rate of Anti-polio Serum Neutralizing Antibodies 4 Weeks After Each Vaccination(Baseline and Weeks 4 and 8)
- All Cohorts: Geometric Mean Titer (GMT) of Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibodies Following Last Dose(Baseline and 4 weeks following the last vaccination (week 8 in adults and young children and week 18 in neonates))
- Neonates: Geometric Mean Fold Rise (GMFR) in Neutralizing Antibody Titer Relative to the Expected Level of Maternal Antibody and Each Pre-dose Value(Baseline and weeks 6, 10, 14, and 18)
- Adults and Young Children: Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibody Titers Following First Dose(Baseline and week 4)
- Adults and Young Children: Geometric Mean Titer (GMT) of Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibodies Following First Dose(Baseline and Week 4)
- Adults and Young Children: Geometric Mean Fold Rise (GMFR) in Neutralizing Antibody Titer Relative to Previous Dose(Baseline and weeks 4 and 8)
- All Cohorts: Type-specific and Multitypic Seroprotection Rate Following Last Dose(Baseline and 4 weeks following the last vaccination (week 8 in adults and young children and week 18 in neonates))
- Adults and Young Children: Type-specific and Multitypic Seroprotection Rate Following First Dose(Baseline and week 4)