Study of Trivalent and Bivalent (Types 1 & 2) Novel Oral Poliomyelitis Vaccines
- Conditions
- Poliomyelitis
- Interventions
- Biological: Novel oral poliomyelitis vaccine type 1 (nOPV1)Biological: Bivalent Oral Poliomyelitis Vaccine (bOPV)Biological: Novel oral poliomyelitis vaccine type 2 (nOPV2)Biological: Novel oral poliomyelitis vaccine type 3 (nOPV3)
- Registration Number
- NCT06137664
- Lead Sponsor
- PATH
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 2400
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Neonates: LD nOPV2 Novel oral poliomyelitis vaccine type 2 (nOPV2) Newborns will receive nOPV2 (10\^5.3 CCID₅₀) at birth, week 6, week 10 and week 14 of life. Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Adults: High-dose (HD) nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Adults:bOPV Bivalent Oral Poliomyelitis Vaccine (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. Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Neonates: MD nOPV1 + LD nOPV2 Novel oral poliomyelitis vaccine type 2 (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. Young Children: Middle-dose (MD) nOPV1 + Low-dose (LD) nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Young Children: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Young Children: Low-dose (LD) nOPV2 Novel oral poliomyelitis vaccine type 2 (nOPV2) Children aged ≥ 1 to \< 5 years old will receive nOPV2 (10\^5.3 CCID₅₀) on Day 1 and Day 29. Young Children: bOPV Bivalent Oral Poliomyelitis Vaccine (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. Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Neonates: MD nOPV1 + LD nOPV2 + MD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 2 (nOPV2) 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. Neonates: MD nOPV1 + LD nOPV2 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: HD nOPV1+ LD nOPV2+ MD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: bOPV Bivalent Oral Poliomyelitis Vaccine (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. Neonates: HD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 3 (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. Neonates: MD nOPV1 + LD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 1 (nOPV1) 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. Neonates: HD nOPV1 + HD nOPV2 + HD nOPV3 Novel oral poliomyelitis vaccine type 3 (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.
- Primary Outcome Measures
Name Time Method Number of Participants with Serious Adverse Events (SAEs) 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 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. 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 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 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.
- Secondary Outcome Measures
Name Time Method Neonates: Type-specific and Multitypic Seroconversion Rate of Anti-polio Serum Neutralizing Antibodies Baseline and weeks 6, 10, 14, and 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.
Multitypic seroconversion refers to seroconversion to multiple types simultaneously, including types 1 \& 2, types 1 \& 3, types 2 \& 3, and types 1 \& 2 \& 3.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) This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
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 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.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) This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
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 This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Neonates: Percentage of Participants Shedding Types 1, 2 and/or 3 Poliovirus Post-vaccination From birth through 18 weeks Stool samples will be analyzed using polymerase chain reaction (PCR) to detect poliovirus types 1, 2, and 3.
Adults and Young Children: Types 1, 2 and 3 Anti-polio Serum Neutralizing Antibody Titers Following First Dose Baseline and week 4 This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
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 This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
Adults and Young Children: Geometric Mean Fold Rise (GMFR) in Neutralizing Antibody Titer Relative to Previous Dose Baseline and weeks 4 and 8 This endpoint will be analyzed in groups who receive nOPV types 1, 2, and 3.
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) 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.Adults and Young Children: Type-specific and Multitypic Seroprotection Rate Following First Dose Baseline and week 4 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.
Trial Locations
- Locations (1)
International Centre for Diarrhoeal Disease Research
🇧🇩Dhaka, Bangladesh