A Phase 2, Randomized, Observer-blind, Controlled, Age De-escalation, Dosage Escalation Study to Assess Safety and Immunogenicity of a Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine in Healthy Young Children, Infants, and Neonates in Bangladesh

PATH1 site in 1 country2,232 target enrollmentMarch 27, 2023

InterventionsNovel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)Sabin Monovalent Oral Poliomyelitis Vaccine Type 1 (mOPV1)

Overview

Phase: Phase 2
Intervention: Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine (nOPV1)
Conditions: Poliomyelitis
Sponsor: PATH
Enrollment: 2232
Locations: 1
Primary Endpoint: Frequency of serious adverse events (SAEs) from the time of first study vaccination through the end of the study
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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 (1320 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 1320 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.

Registry

clinicaltrials.gov

Start Date

March 27, 2023

End Date

May 15, 2026

Last Updated

3 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

PATH

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•for all participants:
•Healthy, as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment of the investigator
•Parent(s) or guardian(s) willing and able to provide written informed consent prior to performance of any study-specific procedure
•Resides in study area and parent understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form \[ICF\] and assessment by the investigator)
•Parent agrees for participant to receive all routine infant and childhood immunizations as per the approved protocol-adjusted schedule
•Inclusion Criteria for Cohort 1 (young children) participants only:
•Male or female child from 1 to less than 5 years of age at the time of initial study vaccination
•Based on documentation, previously received a 3 or 4 dose primary poliomyelitis immunization series containing OPV (may have also received IPV), with last dose received more than 3 months prior to initial study vaccination
•Inclusion Criteria for Cohort 2 (infants) participants only:
•Male or female infant expected to be 6 weeks of age (43rd to 49th day of life \[with day of birth being the first day of life\], inclusive+ 6-day window), at the time of initial study vaccination

Exclusion Criteria

•for all participants:
•For all participants, the presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete "age appropriate" vaccination status with respect to poliovirus vaccines at the time of study vaccine administration. For household members younger than 10 years of age, "age appropriate" vaccination is complete series of trivalent Oral Poliovirus Vaccine (tOPV) or at least three doses of bivalent (types 1 and 3) Oral Poliovirus Vaccine (bOPV) plus a booster fractional dose of IPV (fractional dose Inactivated Polio Vaccine; fIPV). Note: A vaccination series of tOPV or at least three doses of bOPV with our without a booster fractional dose of IPV will be considered sufficient.
•For all participants, having a member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous 3 months before study vaccine administration.
•Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
•Moderate or severe (grade ≥ 2) acute illness at the time of enrollment/first study vaccination - temporary exclusion. Participant with mild (grade 1) acute illnesses may be enrolled at the discretion of the investigator.
•Presence of fever on the day of enrollment/first study vaccination (axillary temperature ≥37.5˚C) - (Temporary exclusion for Cohorts 1 and 2)
•A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
•Evidence of a clinically significant congenital or genetic defect as judged by the investigator
•History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (\> 0.5mg/kg/day of prednisolone (or equivalent)). Topical and inhaler steroids are permitted (unless indicative of a significant chronic illness otherwise excluding the infant/young child)
•Any self-reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member (living under the same roof/in the same building rather than in the same compound)

Arms & Interventions

Group 1: Young Children, nOPV1 10^5.5 CCID50

48 young children aged 1 to \<5 years will receive 2 doses of nOPV1 at a dose level of 10\^5.5 CCID50 on Day 1 and Day 29