Study of a Novel Type 1 Oral Poliomyelitis Vaccine in Bangladesh

Phase 2

Recruiting

• Conditions: Poliomyelitis

• Registration Number: NCT05644184
• Lead Sponsor: PATH

Brief Summary

The purpose of this clinical trial is to assess the safety and tolerability (primary objective), immunogenicity (primary and secondary objectives), fecal shedding of vaccine viruses (secondary objective) and the potential for neurovirulence of shed virus (secondary objective) of a novel oral polio type 1 vaccine, nOPV1, as compared to Sabin monovalent type 1 vaccine controls (mOPV1), in healthy young children (192 subjects), infants (720 subjects), and neonates (1100 subjects).

Detailed Description

This single-center trial is the first clinical assessment of nOPV1 in a pediatric population. It will be a 15-arm, randomized, observer-blind, controlled trial, with Sabin monovalent type 1 vaccine (mOPV1) serving as the control. Enrollment in this pediatric study will be staggered into three age-descending cohorts, Cohort 1 composed of 192 healthy young children 1 to less than 5 years of age who have completed their full routine polio immunization series, Cohort 2 composed of 720 healthy infants 6 weeks of age (+6 days) who will receive only one dose of inactivated poliomyelitis vaccine (IPV) on Day 1, and finally Cohort 3, composed of 1100 healthy poliomyelitis unvaccinated neonates (day of birth +3 days). Participants will receive two or three doses of either nOPV1 at dose levels of 10\^5.5 CCID50, 10\^6.0 CCID50, 10\^6.5 CCID50, 10\^7.0 CCID50 or 10\^7.5 CCID50 or the mOPV control vaccine. The second and third doses of vaccine will be given 28 days following the prior dose. In order to demonstrate the vaccine's ability to reduce fecal shedding following a challenge with the Sabin type 1 strain, the infant cohort will be challenged with mOPV 8 weeks after their last dose of nOPV. Participants will be followed until 28 weeks (young children and neonates) or 32 weeks (infants) after their Day 1 vaccination.

Study Timeline

• Study First Submitted: 2022-11-10
• Study First Submitted QC: 2022-11-30
• Study First Posted: 2022-12-09
• Study Start: 2023-03-27
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-30
• Last Update Posted: 2024-08-01
• Primary Completion: 2026-05-15
• Study Completion: 2026-05-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2012

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Frequency of serious adverse events (SAEs) from the time of first study vaccination through the end of the study	From Day 1 to end of study, up to Day 197 (young children and neonates) or Day 225 (infants)	Serious adverse event is any adverse event that results in any of the following outcomes: 1. Death; 2. Is life-threatening (life-threatening means that the study participant was, in the opinion of the site PI or PATH, at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe).; 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. 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
Frequency of solicited adverse events (AEs) for 7 days (day of vaccination and 6 following days) after each vaccination	From vaccination to 7 days post vaccination	Solicited AEs are pre-specific AEs that are common or known to be associated with vaccination that are actively monitored as potential indicators of vaccine reactogenicity. The following specific solicited AEs will be monitored for this trial: * Fever (axillary temperature ≥ 37.5°C); * Vomiting; * Diarrhea; * Irritability; * Decreased feeding or appetite; * Fatigue or decreased activity
Frequency of unsolicited AEs for 28 days (day of vaccination and 27 following days) after each vaccination	From vaccination to 28 days post vaccination	Unsolicited AEs are any AEs reported spontaneously by the participant's parent, observed by the study personnel during study visits or identified during review of medical records or source documents. In the absence of a diagnosis, abnormal physical examination findings or abnormal clinical safety laboratory test results that are assessed by the investigator to be clinically significant will be reported as an AE.
Post-vaccination frequency of seroconversion of type 1 anti-polio serum neutralizing antibody (NAb).	28 days post second vaccination	Following two doses of nOPV1, at dose levels of 10\^6.5 and 10\^7.0 CCID50/dose, compared to mOPV1, in healthy neonates.; For unvaccinated neonates, seroconversion will be defined as either a minimum 4-fold higher antibody titer relative to the expected level of maternal antibody and seropositivity (reciprocal titer ≥ 8) at the post-vaccination time point among those initially seropositive, or post-vaccination seropositivity among those initially seronegative.

Secondary Outcome Measures

Name	Time	Method
Post-vaccination frequency of seroconversion of type 1 anti-polio serum NAb.	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	To assess the seroconversion rate elicited by nOPV1 at dose levels of 10\^6.5, 10\^7.0 and 10\^7.5 CCID50/dose following one and three doses in healthy neonates compared to mOPV1.; To assess the seroconversion rate elicited by nOPV1 at dose levels of 10\^5.5, 10\^6.0 and 10\^6.5 CCID50/dose following one or two doses in healthy young children compared to mOPV1.; To assess the seroconversion rate elicited by nOPV1 at dose levels of 10\^5.5 and 10\^6.0 CCID50/dose following one or two doses in healthy infants compared to mOPV1.
Type 1 anti-polio serum NAb Geometric Mean Titer (GMT).	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates.
Seroprotection rate, defined as type 1 anti-polio serum NAb reciprocal titer ≥ 8.	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates.
Median type 1 anti-polio serum NAb titers.	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates.
Geometric mean fold rise (GMFR) in NAb titer relative to baseline for post-dose-1 and relative to post-dose-1 for post-dose-2.	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates.
Neurovirulence of shed study vaccine virus from select stool samples as measured by a transgenic mouse neurovirulence test in a subset of infants.	Baseline through to 28 days post initial vaccination (Day 29 through 57 for infants)	Within 28 days of an initial nOPV dose and compared to that of mOPV1.
Post-vaccination GMT ratios of type 1 anti-polio serum NAb, adjusted for baseline immunity.	Baseline and 28 days post vaccination (Day 1 and Day 29 for young children, Day 1, Day 29 and Day 57 for neonates and Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV1, compared to that of mOPV1, following one or two doses in healthy young children, and one, two or three doses in infants and neonates.
Proportion of participants shedding type 1 poliovirus at any and at each post-vaccination stool collection, as assessed by polymerase chain reaction (PCR) in infants and neonates.	Baseline through to 28 days post initial vaccination (Day 29 through to Day 57 for infants; Day 1 through to Day 29 for neonates)	28 days after the initial dose of nOPV1, compared to mOPV1.
Proportion of participants shedding type 1 poliovirus at any and at each post-challenge stool collection, as assessed by PCR in infants.	Day of challenge through to 28 days post challenge (Day 113 through to Day 141 or 169, for infants)	28 days after mOPV challenge compared to mOPV1

Trial Locations

Locations (1)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b); 🇧🇩 Dhaka, Bangladesh