Pakistan Short Interval mOPV1 Compared With Standard Interval mOPV1 and bOPV 1,3

Study Overview
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Brief Summary
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Globally, polio cases have decreased by over 99% since 1988. However, wild poliovirus cases continue in Pakistan. Conflict and lack of access to children due to on-going insecurity in tribal areas present special challenges in interrupting transmission rapidly. There exists limited knowledge on the effect of shorter intervals of mOPV vaccination on immunogenicity levels in young children. The aim of this study is to demonstrate the non-inferiority of shorter intervals (7 and 14 days) between doses of mOPV1 vaccine compared to the customary interval (30 days). A 4th arm will receive bivalent (bOPV) vaccine at standard intervals beginning at 6 weeks of age.

Detailed Description
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This randomized clinical trial which will be conducted in 5 low-income areas in and around Karachi (4 peri-urban, contiguous coastal villages outside Karachi, and one urban squatter settlement) where the Aga Khan University's Department of Paediatrics and Child Health has well-established demographic surveillance with all pregnancies and new births in the area captured through the system. The study participants will be enrolled from birth until 102 days. Subjects will be randomized to one of four trial arms. All children will receive tOPV at birth. At 42 days (6 weeks) of age, three study arms will receive a dose of mOPV1 whereas the fourth arm will receive a dose of bOPV1&3 as per protocol. Then 7 or 14 or 30 days later, the study participants in Arms A, B, and C will receive a second dose of mOPV1 while a second dose of bOPV 1&3 will be given to participants in Arm D at 30 days. Name and description of products: Standard trivalent oral poliovirus vaccine (tOPV), in a 10:1:6 formulation, containing at least 106 TCID50 of Sabin -strain poliovirus type 1, at least 105 TCID50 of Sabin-strain poliovirus type 2 and at least 105.8 TCID50 of Sabin-strain poliovirus type 3. Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1. The bivalent oral polio vaccine containing at least 106 CCID50 of Sabin poliovirus type 1 and 105•8 CCID50 of Sabin poliovirus type 3. Sample Size: To show non-inferiority of a 2-dose mOPV1 schedule with shorter-intervals (either 7 or 14 days) [intervention] compared to a 2-dose mOPV1 schedule administered at 30-day intervals [control], and a 2-dose bOPV13 schedule administered at a 30-day interval (control) assuming a power of 0.90 (beta) and p of 0.05 (alpha), we require a sample of 139 for each study group, for a total of 556 subjects. To compensate for drop out, attrition and insufficient sera for laboratory testing, an inflated (by   50%) sample size of 200 in each group will be used (total sample size of 800) Efficacy Endpoints: The primary endpoint is seroconversion with antibodies to poliovirus type 1 following a two-dose schedule of mOPV1 given at intervals of 7 and 14 days compared to mOPV1 and bOPV1&3 given at the standard interval of 30 days.. The secondary endpoint is seroconversion following the birth dose of tOPV. All samples will be processed at the Centers of Disease Control and Prevention CDC) Laboratories (a Global Specialized Polio Network Laboratory).

Official Title
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Comparison of Immunogenicity of Type 1 mOPV Administered at Short Intervals With Type 1 mOPV1 and Type 1 & 3 bOPV Oral Polio Vaccine Given at Standard Intervals in Pakistan:A Randomized Trial

Conditions
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Polio

Intervention / Treatment
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* Drug: mOPV1
* Drug: bOPV 1,3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants > 2.5 kg birth weight Immediate cry No neonatal IMCI danger signs Not planning to travel away during entire the study period (birth-102 days) Exclusion Criteria: High-risk newborns will be excluded, as well as newborns requiring hospitalization Birth weight below 2.5 kg Cry >2 minutes With any neonatal IMNCI danger signs Residence >30 km from study site Family is planning to be absent during the birth - 102 day study period. A diagnosis or suspicion of immunodeficiency disorder (either in the participant or in a member of the immediate family - e.g. several early infant deaths, household member on chemotherapy) will render the newborn ineligible for the study.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 24 Hours

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: mOPV1- Arm A<br>Arm A will be administered a second dose of mOPV1 seven days after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at day 79. | Drug: mOPV1<br>* Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.<br>* Other names: Monovalent type 1 oral poliovirus vaccine;|
| Experimental: mOPV1- Arm B<br>Arm B will be administered a second dose of mOPV1 fourteen days after after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at 86 days. | Drug: mOPV1<br>* Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.<br>* Other names: Monovalent type 1 oral poliovirus vaccine;|
| Experimental: mOPV1-Arm C<br>Arm C will receive the second dose of mOPV1 thirty days after the 42 day mOPV1 index dose.Second dose of tOPV2 will be given at 102 days. | Drug: mOPV1<br>* Monovalent type 1 oral poliovirus vaccine (mOPV1) containing at least106 TCID50 of Sabin- strain poliovirus type 1.<br>* Other names: Monovalent type 1 oral poliovirus vaccine;|
| Experimental: Arm D- bOPV1,3<br>Arm D will be administered a second dose of bOPV1,3 thirty days after the 42 day bOPV1,3 index dose.Second dose of tOPV2 will be given at day 102. | Drug: bOPV 1,3<br>* The bivalent vaccine containing at least 106 CCID50 of Sabin poliovirus type 1 and 105•8 CCID50 of Sabin poliovirus type 3.<br>* Other names: Bivalent Oral Polio Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion with antibodies to poliovirus type 1 following a two-dose schedule of mOPV1 given at intervals of 7 and 14 days compared to mOPV1 and bOPV1&3 given at the standard interval of 30 days. | Humoral immunity: Sera collected at birth (cord blood or peripheral blood), at 42 days, at 79 days, at 86 days, or at 102 days (depending on study arm) will be examined for the presence (detectable) or absence of neutralizing antibodies to all three poliovirus serotypes. A reciprocal titer of >8 is considered to indicate the presence of neutralizing antibodies. For participants with detectable antibodies, seroconversion is defined as a 4-fold increase over the expected decline of maternally-derived antibodies (half-life assumed to be 28 days). | Participants will be followed till 102 days after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion following the birth dose of tOPV. |  | At birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polio virus type 1,2,3, Poliovaccine-Oral, Poliovaccine, Trivalent Oral Polio vaccine, Monovalent oral polio vaccine, Bivalent Oral polio vaccine