Study to Evaluate Safety and Immunogenicity of nOPV2 at Different Intervals in Infants

Study Overview
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Brief Summary
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Study to determine immunogenicity and safety following administration of 2 doses of novel oral poliovirus vaccine type 2 (nOPV2) given at different intervals of 1 week or 2 weeks or the standard 4-week interval in infants

Detailed Description
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This will be a multicenter, randomized, controlled, open-label, parallel-group Phase III study in healthy infants aged 6 to 8 weeks who have never been vaccinated against poliomyelitis. Approximately 900 infants will be included in the study and randomized with a 1:1:1 ratio to the following treatment groups: Group A: approximately 300 subjects to receive 2 doses of nOPV2 administered 1 week apart, at Day 0 and Day 7; Group B: approximately 300 subjects to receive 2 doses of nOPV2 administered 2 weeks apart, at Day 0 and Day 14; Group C (control group): approximately 300 subjects to receive 2 doses of nOPV2 administered 4 weeks apart, at Day 0 and Day 28. A total of 4 on-site visits are planned. Approximately 7 days after each administration of study vaccine, a phone call or on-site visit will be performed to monitor subjects' safety and review with the subject's parent(s)/guardian(s) any solicited AEs reported in the electronic diary card. All subjects will have a safety follow-up phone call 6 months after the last dose of study vaccine.

Official Title
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A Phase III Open-label Randomized Controlled Study to Evaluate the Safety and Immunogenicity of nOPV2 at Different Intervals of Administration in Infants

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: nOPV2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants aged 6 to 8 weeks with birth weight > 2,500 g. Healthy infants 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 from participating in the study as established by the medical history and physical examination. Written informed consent obtained from 1 or 2 parent(s) or legal guardian(s) as per country regulations. Exclusion Criteria: Infants who have received previous vaccination against poliomyelitis. Infants with anyone under 5 years of age in their household (living in the same house or apartment unit) who does not have the complete age appropriate vaccination status with respect to poliovirus vaccines at the time of study vaccine administration according to the Dominican Republic National Immunization Program (NIP). Infants having a member of their household (living in the same house or apartment unit) who is under 6 months of age at the moment of study vaccine administration. Infants having a member of their household (living in the same house or apartment unit) who has received oral poliomyelitis vaccine (OPV) in the previous 3 months before study vaccine administration. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus infection in the potential participant or any member of the subject's household. 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 vaccine or to any antibiotics that share molecular composition with the nOPV2 vaccine. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Acute severe febrile illness on the 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.). 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. Infants from multiple births or born prematurely (< 37 weeks of gestation)

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 doses, 1 week apart<br>Administration of 2 doses of nOPV2, 1 week apart | Biological: nOPV2<br>* Novel Oral Poliomyelitis Type 2 Vaccine<br>|
| Experimental: 2 doses, 2 week apart<br>Administration of 2 doses of nOPV2, 2 weeks apart | Biological: nOPV2<br>* Novel Oral Poliomyelitis Type 2 Vaccine<br>|
| Active Comparator: 2 doses, 4 week apart<br>Administration of 2 doses of nOPV2, 4 weeks apart | Biological: nOPV2<br>* Novel Oral Poliomyelitis Type 2 Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate at 1 week interval | Cumulative seroconversion rate of type 2 polio neutralizing antibodies 28 days following administration of 2 doses of nOPV2 in 1-week interval to infants 6 to 8 weeks of age | 4 weeks | 
| Seroconversion rate at 2 weeks interval | Cumulative seroconversion rate of type 2 polio neutralizing antibodies 28 days following administration of 2 doses of nOPV2 in 2-weeks intervals to infants 6 to 8 weeks of age | 4 weeks | 
| Seroconversion rate at 4 weeks interval | Cumulative seroconversion rate of type 2 polio neutralizing antibodies 28 days following administration of 2 doses of nOPV2 in 4-weeks intervals to infants 6 to 8 weeks of age | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibodies at 1 week interval | Geometric mean and median titers of type 2 polio neutralizing antibodies at Day 0 and 28 days after the second dose of nOPV2 when administered 1 week apart. | 4 weeks | 
| Neutralizing antibodies at 2 weeks interval | Geometric mean and median titers of type 2 polio neutralizing antibodies at Day 0 and 28 days after the second dose of nOPV2 when administered 2 weeks apart. | 4 weeks | 
| Neutralizing antibodies at 4 weeks interval | Geometric mean and median titers of type 2 polio neutralizing antibodies at Day 0 and 28 days after the second dose of nOPV2 when administered 4 weeks apart. | 4 weeks | 
| Serious Adverse Events (SAEs) and Important Medical Events (IMEs) | Incidence of SAEs and IMEs from the date of informed consent throughout the study period in all groups by severity and by causal association. | 6 months | 
| Solicited Adverse Events (AEs) | Incidence of mild, moderate and severe solicited AEs (fever, vomiting, abnormal crying, drowsiness, loss of appetite, diarrhea and irritability) for 7 days after each dose of study vaccine in all groups. | 1 week | 
| Unsolicited Adverse Events (AEs) | Incidence of mild, moderate and severe solicited AEs (fever, vomiting, abnormal crying, drowsiness, loss of appetite, diarrhea and irritability) for 28 days after each dose of study vaccine in all groups. | 4 weeks |