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.
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: * Absence of safety concerns upon the safety data reviews occurring at least 8 days after receipt of the first dose of 107.5 CCID50 nOPV1 or 107.5 CCID50 nOPV3 by the first 60 IPV-vaccinated infants enrolled in each of the Phase 2 monovalent trials CVIA 093 and CVIA 101, respectively (the first 45 nOPV:15 mOPV participants randomized per dose pair). * Favorable immunogenicity data (homotypic anti-polio serum neutralizing antibody titers) from the Phase 2 monovalent nOPV1 study (CVIA 093) in IPV-vaccinated infants, and the Phase 2 monovalent nOPV3 study (CVIA 101) in young children. Stage 2 will consist of dose exploration in neonates (Cohort 3). In Cohort 3, Groups 7-14, 2100 neonates will be randomly allocated in a 3:3:3:3:3:3:2:1 ratio, respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
2,400
Live attenuated novel poliomyelitis virus type 1 at two different dosages, containing middle-dose (MD) 10\^6.0, or high-dose (HD) 10\^6.5 CCID₅₀/dose
Live attenuated novel poliomyelitis virus type 2 administered at low-dose (LD) 10\^5.3 and HD 10\^5.6 CCID₅₀/dose.
Live attenuated novel poliomyelitis virus type 3 at two different dosages, containing MD 10\^6.0, or HD 10\^6.5 CCID₅₀/dose.
Live attenuated poliomyelitis viruses types 1 and 3 (Sabin strains). Each dose (2 drops = 0.1 mL) contains not less than 10\^6.0 infective units of type 1 and 10\^5.8 of type 3.
International Centre for Diarrhoeal Disease Research
Dhaka, Bangladesh
NOT_YET_RECRUITINGInternational Centre for Diarrhoeal Disease Research
Dhaka, Bangladesh
RECRUITINGNumber of Participants with Serious Adverse Events (SAEs)
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.
Time frame: From the time of first study vaccination through the end of the study (197 days)
Number of Participants with Solicited Adverse Events (AEs) for 7 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.
Time frame: 7 days (day of vaccination and 6 following days) after each vaccination
Number of Participants with Unsolicited AEs for 28 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.
Time frame: 28 days (day of vaccination and 27 following days) after each vaccination
Neonates: Seroconversion Rate of Types 1, 2, and 3 Anti-polio Serum Neutralizing Antibodies 28 Days After Last Vaccination
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.
Time frame: Baseline and 28 days following the last vaccination (week 18)
Neonates: Seroconversion Rate of Types 1, 2, and 1 & 2 Combined Anti-polio Serum Neutralizing Antibodies 28 Days After Last Vaccination
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.
Time frame: Baseline and 28 days following the last vaccination (week 18)
Neonates: Type-specific and Multitypic Seroconversion Rate of Anti-polio Serum Neutralizing Antibodies
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. Multitypic seroconversion refers to seroconversion to multiple types simultaneously, including types 1 \& 2, types 1 \& 3, types 2 \& 3, and types 1 \& 2 \& 3.
Time frame: Baseline and weeks 6, 10, 14, and 18
Adults and Young Children: Type-specific and Multitypic Seroconversion Rate of Anti-polio Serum Neutralizing Antibodies 4 Weeks After Each Vaccination
For previously vaccinated cohorts, seroconversion will be defined as either a minimum 4-fold rise in titer relative to the baseline value among those initially seropositive, or post-vaccination seropositivity among those seronegative at baseline. This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and Weeks 4 and 8
All Cohorts: Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibody Titers Following Last Dose
This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and 4 weeks following the last vaccination (week 8 in adults and young children and week 18 in neonates)
Adults and Young Children: Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibody Titers Following First Dose
This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and week 4
All Cohorts: Geometric Mean Titer (GMT) of Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibodies Following Last Dose
This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and 4 weeks following the last vaccination (week 8 in adults and young children and week 18 in neonates)
Adults and Young Children: Geometric Mean Titer (GMT) of Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibodies Following First Dose
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This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and Week 4
All Cohorts: Type-specific and Multitypic Seroprotection Rate Following Last Dose
Seroprotection is defined as types 1, 2 and 3 anti-polio serum neutralizing antibody reciprocal titer ≥ 8. This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: 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
Seroprotection is defined as types 1, 2 and 3 anti-polio serum neutralizing antibody reciprocal titer ≥ 8. This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and week 4
Adults and Young Children: Geometric Mean Fold Rise (GMFR) in Neutralizing Antibody Titer Relative to Previous Dose
This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and weeks 4 and 8
Neonates: Geometric Mean Fold Rise (GMFR) in Neutralizing Antibody Titer Relative to the Expected Level of Maternal Antibody and Each Pre-dose Value
This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Time frame: Baseline and weeks 6, 10, 14, and 18
Neonates: Percentage of Participants Shedding Types 1, 2 and/or 3 Poliovirus Post-vaccination
Stool samples will be analyzed using polymerase chain reaction (PCR) to detect poliovirus types 1, 2, and 3.
Time frame: From birth through 18 weeks