Study of a Novel Type 3 Oral Poliomyelitis Vaccine in Panama

Phase 2

Recruiting

• Conditions: Poliomyelitis
• Interventions: Biological: Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3); Biological: Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)

• Registration Number: NCT05654467
• 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 3 vaccine, nOPV3, as compared to Sabin monovalent type 3 vaccine controls (mOPV3), in healthy young children (192 subjects), infants (860 subjects), and neonates (480 subjects).

Detailed Description

This multicentered, 12-arm phase 2 study will be the first pediatric evaluation of nOPV3 in healthy young children, infants, and newborns. This trial will be initiated once results in the adult phase 1 study of nOPV3 indicate that there are no safety concerns, and that the vaccine elicits demonstrable immunogenicity. Additionally, prior to enrolling into cohort 2, the adult phase 1 data must show no concerning signals of reversion of attenuating sites from a subset of Next Generation Sequencing.

This study is intended to provide critical data on safety, immunogenicity, and genetic stability, as well as to demonstrate the vaccine's ability to reduce fecal shedding following a challenge with the Sabin type 3 strain.

Enrollment in this pediatric study will be staggered into three age-descending cohorts of 6 treatment groups of escalated target dose levels for the nOPV3 vaccine: cohort 1 composed of 192 healthy young children 1 to \<5 years of age who have completed their full routine polio immunization series; cohort 2 composed of 860 healthy infants 6 weeks of age not previously vaccinated (OPV/IPV) who will be primed with a dose of inactivated poliomyelitis vaccine (IPV) prior to OPV3 vaccination \[a subset, of the infants (n=360) will also receive the challenge virus\]; and cohort 3, composed of 480 healthy poliomyelitis unvaccinated neonates (day of birth +3 days).

Progression into the next cohort and groups within cohorts will depend on safety evaluations of the prior Phase 1 adult trial and Day 8 safety evaluation of the previous groups in prior cohorts in the study.

Study Timeline

• Study First Submitted: 2022-12-07
• Study First Submitted QC: 2022-12-14
• Study First Posted: 2022-12-16
• Study Start: 2023-12-05
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-27
• Last Update Posted: 2024-02-28
• Primary Completion: 2025-11-20
• Study Completion: 2025-11-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1532

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Groups 2, 4 and 6: Young Children, mOPV3	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	48 young children aged 1 to \<5 years will receive 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 1 and Day 29
Group 1: Young Children, nOPV3 10^5.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29
Group 3: Young Children, nOPV3 10^6.0 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 1 and Day 29
Group 13: Neonates, nOPV3 10^5.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29.
Group 9: Infants, nOPV3 10^5.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 9: Infants, nOPV3 10^5.5 CCID50	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 15: Neonates, nOPV3 10^6.0 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^6.0 CCID50 on Day 1 and Day 29.
Group 5: Young Children, nOPV3 10^6.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	48 young children aged 1 to \<5 years will receive 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 1 and Day 29
Group 7: Infants, nOPV3 10^5.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Groups 8, 10 and 12: Infants, mOPV3	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 7: Infants, nOPV3 10^5.5 CCID50	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	240 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^5.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 11: Infants, nOPV3 10^6.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	140 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 11: Infants, nOPV3 10^6.5 CCID50	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	140 infants aged 6 weeks (+6 days) will receive 1 dose of IPV on Day 1, then 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 29 and Day 57, and a challenge dose of mOPV on Day 113.
Group 17: Neonates, nOPV3 10^6.5 CCID50	Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine (nOPV3)	120 neonates (day of birth + 3 days) will receive 2 doses of nOPV3 at a dose level of 10\^6.5 CCID50 on Day 1 and Day 29.
Groups 14, 16 and 18: Neonates, mOPV	Sabin Monovalent Oral Poliomyelitis Vaccine Type 3 (mOPV3)	120 neonates (day of birth + 3 days) will receive 2 doses of mOPV3 at a dose level of ≥ 10\^5.8 CCID50 on Day 1 and Day 29

Primary Outcome Measures

Name	Time	Method
Frequency of serious adverse events (SAEs)	Up to last visit for last subject, around 18 months	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 PIs 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. 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.
Frequency of solicited adverse events (AEs) for 7 days (day of vaccination and 6 following days) after each vaccination	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
Post-vaccination frequency of seroconversion of type 3 anti-polio serum neutralizing antibody (NAb) in infants.	28 days post second vaccination	For previously vaccinated cohorts, seroconversion will be defined as a minimum 4-fold rise in titer relative to the baseline value among those initially seropositive.
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.

Secondary Outcome Measures

Name	Time	Method
Seroprotection rate, defined as type 3 anti-polio serum NAb reciprocal titer ≥ 8	Baseline and 28 days post vaccination (Day 1, Day 29 and Day 57 for young children and neonates; Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV3, compared to that of mOPV3, following one or two doses in healthy young children, infants, and neonates.
Type 3 anti-polio serum NAb Geometric Mean Titer (GMT)	Baseline and 28 days post vaccination (Day 1, Day 29 and Day 57 for young children and neonates;Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV3, compared to that of mOPV3, following one or two doses in healthy young children, 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 postvaccination (Day 1, Day 29 and Day 57 for young children and neonates; Day 29, Day57 and Day 85 for infants)	Elicited by nOPV3, compared to that of mOPV3, in healthy young children, infants,and neonates.
Post-vaccination frequency of seroconversion of type 3 anti-polio serum NAb	Baseline and 28 days post vaccination (Day 1 and Day 29 for neonates; Day 29,Day 57 and Day 85 for infants; Day 1, Day 29 and Day 57 young children)	For previously vaccinated cohorts, seroconversion will be defined as a minimum 4-fold rise in titer relative to the baseline value among those initially seropositive and for unvaccinated neonates, seroconversion will be defined as a minimum 4-fold higher antibody titer relative to the expected level of maternal antibody.
Median type 3 anti-polio serum NAb titers	Baseline and 28 days post vaccination (Day 1, Day 29 and Day 57 for young children and neonates; Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV3, compared to that of mOPV3, following one or two doses in healthy young children, 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 1 through to Day 29 for neonates)	Within 28 days of an initial nOPV dose and compared to that of mOPV3
Post-vaccination GMT ratios of type 3 anti-polio serum NAb, adjusted for baseline immunity	Baseline and 28 days post vaccination (Day 1, Day 29 and Day 57 for young children and neonates; Day 29, Day 57 and Day 85 for infants)	Elicited by nOPV3, compared to that of mOPV3, following one or two doses in healthy young children, infants, and neonates.
Proportion of participants shedding type 3 poliovirus at any and at each post-vaccination stool collection, as assessed by polymerase chain reaction (PCR) in infants	Baseline through to 28 days post initial vaccination (Day 29 through to Day 57 for infants)	After the initial dose of nOPV3, compared to mOPV3
Proportion of participants shedding type 3 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, for infants)	In participants negative for type 3 poliovirus in their last pre-challenge stool sample

Trial Locations

Locations (3)

Cevaxin - 24 de Diciembre; 🇵🇦 Panama City, Panama

Cevaxin - Chorrera; 🇵🇦 Panama City, Panama

Cevaxin-- Avenida Mexico; 🇵🇦 Panama City, Panama