A Phase 2, Randomized, Observer-Blind, Controlled, Age De-escalation, Dosage Escalation Study to Assess the Safety and Immunogenicity of a Novel Live Attenuated Type 3 Oral Poliomyelitis Vaccine in Healthy Young Children, Infants, and Neonates in Panama
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Poliomyelitis
- Sponsor
- PATH
- Enrollment
- 1532
- Locations
- 3
- Primary Endpoint
- Frequency of serious adverse events (SAEs)
- Status
- Recruiting
- Last Updated
- 2 years ago
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Frequency of serious adverse events (SAEs)
Time Frame: 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
Time Frame: 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.
Time Frame: 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
Time Frame: 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 Outcomes
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))