A Study to Evaluate the Safety and Immunogenicity of Novel Oral Polio Vaccine

April 18, 2023 updated by: Fidec Corporation

A Phase 2 Study to Evaluate the Safety and Immunogenicity of Two Novel Oral Polio Type 2 (nOPV2) Vaccine Candidates in Healthy Children Aged 1 to 5 Years and in Healthy Bivalent Oral Polio Vaccine-inactivated Polio Vaccine (bOPV-IPV) Vaccinated Infants

This will be a single center, age de-escalation, partly-blinded, randomized study.

The trial will be performed with the participation of 100 healthy children age 1-5 years who have been vaccinated with inactivated polio vaccine (IPV) and/or oral polio vaccine (OPV) in their first year of life and of 648 healthy 6 week-old infants, who will be pre-vaccinated with bOPV-IPV before being randomized to study groups. The allocation of 18-22 week-old infants to groups will be performed in a randomized manner. Following completion and Data Safety Monitoring Board (DSMB) review of follow-up for general safety data (Serioius Adverse Events -SAEs-, Important Medical Events -IMEs- and severe adverse events -AEs), a DSMB recommendation to proceed will result in randomization of the final cohort of infants. Allocation of 1 to 5 year-old children to groups will be performed in a randomized manner.

The DSMB will establish and continuously assess stopping rules for safety.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

1025

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Panamá, Panama
        • Cevaxin Vaccination Center
    • Chiriquí
      • David, Chiriquí, Panama
        • Cevaxin Vaccination Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 5 years (Child)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. For Cohort A children enrolled at 1 to 5 years of age who have previously been fully vaccinated according to MoH recommendations with OPV and/or IPV.
  2. For Cohort B infants enrolled at 6 weeks of age (-1, + 2 weeks) with birth weight >2,500 gm. To be eligible to continue into the experimental phase of the study infants must be vaccinated with 3 doses of bOPV and one dose of IPV prior to administration of the study vaccine at 18-22 weeks of age to take into account the visit windows for enrollment (age 6 weeks, -1 or + 2 weeks) and subsequent OPV vaccination windows (± 1 week). The last polio vaccine must have been administered at least 4 weeks prior to the first dose of study vaccine. Subjects in Cohort B who do not complete the three routine vaccination visits will be replaced in the study, and their parents/guardians will be encouraged to complete the primary vaccinations series.
  3. Healthy children without obvious medical conditions like immunodeficiency diseases, severe congenital malformations, severe neurological diseases or any other disease that require high doses of corticosteroids or immunotherapies that preclude the subject to be in the study as established by the medical history and physical examination.
  4. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations.

Exclusion Criteria:

  1. For all participants the presence of anyone under 10 years of age in the subject'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 18 months age appropriate vaccination is at least three (3) doses of IPV. For household members between 18 months and 10 years "age appropriate" vaccination is at least three (3) doses of IPV or tOPV plus one (1) booster dose of any antipolio vaccine.
  2. For all participants having a member of the subject's household (living in the same house or apartment unit) who is under 6 months of age at the moment of study vaccine administration.
  3. For all participants having a member of the subject's household (living in the same house or apartment unit) who has received OPV in the previous 3 months before study vaccine administration.
  4. For Cohort A: receipt of polio vaccines within the 3 months prior to the administration of the study vaccine (number of previous polio vaccine doses to be documented). Any other vaccine 4 weeks before study entry.
  5. For Cohort A: any participating children attending day care or pre-school during their participation in the study until one month after their last nOPV2 administration.
  6. For Cohort B: any receipt of polio vaccines prior to administration of the study vaccine other than 3 doses of bOPV and 1 dose of IPV.
  7. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection in the potential participant or any member of the subject's household.
  8. Family history of congenital or hereditary immunodeficiency.
  9. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
  10. Known allergy to any component of the study vaccines or to any antibiotics, that share molecular composition with the nOPV2 vaccines.
  11. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections (of IPV).
  12. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  13. Acute severe febrile illness at day of vaccination deemed by the Investigator to be a contraindication for vaccination (the child can be included at a later time if within age window and all inclusion criteria are met.).
  14. Subject who, in the opinion of the Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nOPV2 Candidate 1 (monovalent oral poliovirus type1)

Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1.

Cohort B: 6 weeks Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 1.

Cohort A: 150 IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1 or 2; two 10‸6 CCID50 (50% cell culture infective dose) doses separated by 28 days.

Cohort B: 972 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 10‸5 CCID50 dose of candidate 1 or 2.

Experimental: nOPV2 Candidate 2 (monovalent oral poliovirus type2)

Cohort A: IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 2.

Cohort B: Infants vaccinated with 3 doses of bOPV and 1 dose of IPV, followed with 1 dose of candidate 2.

Cohort A: 150 IPV and/or OPV vaccinated participants aged 1 to 5 years vaccinated with candidate 1 or 2; two 10‸6 CCID50 (50% cell culture infective dose) doses separated by 28 days.

Cohort B: 972 infants enrolled at 6 weeks of age (-7 to +14 days) vaccinated with 3 doses of bOPV at 6, 10 and 14 weeks of age and 1 dose of IPV at 14 weeks of age, followed at 18-22 weeks of age with one 10‸5 CCID50 dose of candidate 1 or 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Single Dose Seroprotection Rate
Time Frame: 2 months
Seroprotection rate of type 2 polio neutralizing antibodies at Day 28 following a single 105 or 106 CCID50 dose of nOPV2 candidates in all groups. Seroprotection rate is defined as the percentage of subjects with type 2-specific antibody titers ≥ 1:8 per group.
2 months
Serious Adverse Reactions (SARs), Severe AEs and Important Medical Reactions (IMRs) Incidence
Time Frame: 6 months
Number of subjects experiencing Serious Adverse Reactions (SAR), severe AR and IMR, i.e. SAEs, severe AEs (grade 3), or IMEs considered consistent with a causal association with study vaccines as of the informed consent signature date and throughout the study period in all groups.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seroconversion Rates Comparison
Time Frame: 2 months
Seroconversion rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study. Seroconversion is defined as a change from seronegative to seropositive, and in seropositive subjects, as an antibody titer increase of ≥ 4 fold over baseline (Day 0) titers corrected for maternal antibodies titers where applicable/age-appropriate.
2 months
Any Other SAEs, AEs and IMEs Incidence
Time Frame: 6 months
Number of participants experiencing any other SAE, any solicited AE, any unsolicited AEs and any IME as well as any clinical laboratory deviation considered consistent with causal association to study vaccine (primary objective) following one or two doses of either nOPV2 candidates.
6 months
Seroprotection Rates Comparison
Time Frame: 2 months

Seroprotection rates against type 2 of one or two 106 CCID50 doses of both nOPV2 vaccine candidates in healthy children aged 1 to 5 years and of two doses of both nOPV2 vaccine candidates at both 105 and 106 CCID50 dose levels at approximately 22 weeks of age in infants previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this immunogenicity with a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study (M2) designed and performed to serve as a control for the current study.

Seroprotection rate is defined as the percentage of subjects with type 2-specific neutralizing antibody titers ≥ 1:8 per group.

2 months
Viral Shedding
Time Frame: 2 months

Level of viral shedding in stool at fixed time points following administration of one or two doses of both nOPV2 candidates at both 105 and 106 CCID50 dose levels in infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and compare this shedding to a control sample of participants receiving the same vaccination schedule followed by one or two doses of Sabin mOPV2 in a prior study designed to serve as a control for the current study.

This is determined by measuring the median number of days taken to get stool cultures negative for poliovirus presence (TTCN stands for median time to culture negative). Kaplan-Meier methods were used to describe the time to cessation of shedding for any shedding (PCR detection).

2 months
Neurovirulence
Time Frame: 2 months

Potential for neurovirulence of virus isolated from a subset of stool samples of infants at approximately 18-22 weeks of age after having been previously vaccinated with 3 doses of bOPV and 1 dose of IPV, and following a single dose of both nOPV2 candidates at the 106 CCID50 dose level, as measured in an animal model, and compare this with a control sample (M2 study).

For each of the children / infants receiving a 106 CCID50 dose of the 2018 cohorts as well as all participants in study M2, an exploratory endpoint sample (EES) of poliovirus shed in stools following the first dose was identified, if possible, with which to perform a modified neurovirulence test in a transgenic mouse model. Data from each sample tested was summarized by group per vaccine candidate. The proportion of mice paralyzed and the odds ratio of paralysis from the single-dose assay were the primary means of comparison of neurovirulence of shed virus between each candidate and the Sabin mOPV2 control samples.

2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2018

Primary Completion (Actual)

February 19, 2020

Study Completion (Actual)

February 19, 2020

Study Registration Dates

First Submitted

May 8, 2018

First Submitted That Met QC Criteria

June 12, 2018

First Posted (Actual)

June 13, 2018

Study Record Updates

Last Update Posted (Actual)

January 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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