A Study to Evaluate Safety and Immunogenicity of tOPV in 1 to 5 Years and at 6 Weeks of Age

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety (serious adverse events [SAEs]), and severe adverse events [AEs] (grade 3 according to CTCAE 4.03) after one dose of SABIN tOPV in 1-5 year-old children and three doses of SABIN tOPV in 6 week-old infants, and immunogenicity (seroprotection rates for all 3 serotypes) 28 days after three doses of SABIN tOPV in vaccine-naïve infants.

Detailed Description
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This will be a single center, open study in children (aged 1 to 5 years) and vaccine-naïve infants, as follows: 50 OPV-vaccinated children aged 1 to 5 years to receive 1 dose of tOPV (Group 1); 104 vaccine-naïve infants to receive 3 doses of tOPV administered 28 days apart (Group 2)

Official Title
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A Phase 4 Study to Evaluate the Safety and Immunogenicity of Trivalent Oral Polio Vaccine in Healthy Polio Vaccinated Children 1 to 5 Years of Age and in Healthy Unvaccinated Infants at 6 Weeks of Age in the Dominican Republic

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: Oral Polio Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: Group 1- Children aged 1-5 years, previously vaccinated with ≥ 3 doses of OPV. Group 2- Infants aged 6 weeks (-7 to +14 days) with no previous polio vaccinations. Healthy without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination. Written informed consent obtained from 1 or 2 parents or legal guardians as per Dominican Republic regulations. Exclusion Criteria: Previous Vaccinations: Group 1: Previous vaccination against poliovirus outside of the national immunization schedule and any vaccine in the previous 4 weeks. Group 2: Any vaccination against poliovirus Group 2: Infants with birth weight (BW) < 2,500 gm. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection. Family history of congenital or hereditary immunodeficiency. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine). Known allergy to any component of the study vaccines or to any antibiotics. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. 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 in/exclusion criteria are met). Member of the subject's household (living in the same house or apartment unit) has received OPV in the last 3 months, or is scheduled to receive OPV during the study period. 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.

Ages Eligible for Study
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Minimum Age: 5 Weeks
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Polio Vaccine<br>Opvero™ (oral) is a trivalent, live attenuated poliomyelitis virus vaccine containing at least 6.0 log 50% cell culture infective dose (CCID50) of LS c2ab strain of live attenuated polio virus type 1, 5.0 log CCID50 of P712, Ch, 2ab strain of live attenuated polio virus type 2, 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. Excipients: human albumin, HEPES buffer solution, magnesium chloride solution (containing polysorbate 80 and phenol red), hydrochloric acid or sodium hydroxide for pH adjustment. The vaccine is presented as a suspension for oral administration. One dose of vaccine (0.1 ml) is contained in two drops which are delivered from the dropper supplied with the multidose container. | Biological: Oral Polio Vaccine<br>* Opvero™ (oral) is a trivalent, live attenuated poliomyelitis virus vaccine containing at least 6.0 log 50% cell culture infective dose (CCID50) of LS c2ab strain of live attenuated polio virus type 1, 5.0 log CCID50 of P712, Ch, 2ab strain of live attenuated polio virus type 2, 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. Excipients: human albumin, HEPES buffer solution, magnesium chloride solution (containing polysorbate 80 and phenol red), hydrochloric acid or sodium hydroxide for pH adjustment. The vaccine is presented as a suspension for oral administration. One dose of vaccine (0.1 ml) is contained in two drops which are delivered from the dropper supplied with the multidose container.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAEs and AEs G3 | Number of subjects experiencing SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine 28 days after three doses of SABIN tOPV in vaccine-naïve infants in Dominican Republic. | 6 months | 
| Seroprotection Rate | Seroprotection rate of type-specific polio neutralizing antibodies at Day 84, 28 days after the third dose of SABIN tOPV in infants (Group 2). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing Antibodies 1 | Median titers of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2). | 3 months | 
| Seroconversion Rate | Seroconversion rate of type-specific neutralizing antibodies at Day 28 for Group 1, and at Day 84 for Group 2. | 3 months | 
| Neutralizing Antibodies 2 | Geometric mean antibody titers (GMT) of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2). | 3 months | 
| Seroprotection Rates | Seroprotection rates of type-specific neutralizing antibodies at Days 0 and 28 in Group 1 and at Day 0 in Group 2. | 4 weeks |