A Study to Evaluate Immunogenicity of Intramuscular Full-Dose and Intradermal Fractional Dose of IPV

Study Overview
=================
Brief Summary
-----------------
The study will assess and compare the immune response to full-dose inactivated polio vaccines (IPV) via intramuscular (IM) administration and of the fractional dose of inactivated poliovirus vaccine (f-IPV) via intradermal (ID) administration, in different schedule combinations in the Expanded Program on Immunization (EPI) primary series.

Detailed Description
-----------------
This study prioritizes comparisons involving two-dose regimens recently recommended by the World Health Organization (WHO) Strategic Advisory Group of Experts on immunization (SAGE) and Pan American Health Organization (PAHO) in response to global IPV supply shortages 21. Furthermore, the study will provide data on the comparative humoral immunogenicity of various schedules to inform polio immunization policy for the post-eradication era. The study population will include infants in Dominican Republic and Panama. Absence of wild and circulating vaccine derived polioviruses along with the lack of regular Supplementary Immunization Activities (SIAs) in the Latin America region provide an ideal epidemiologic setting to study polio vaccine immunogenicity. Infants will receive two or three doses of full-dose IPV IM or f-IPV ID, in two schedules (10, 14 and 36 weeks and 14 and 36 weeks). Immunological and safety assessments will be made after one dose, two doses and three doses. A total of 773 infants will be enrolled and distributed into 4 groups, according to a randomization scheme. During the study period, infants will be administered other concomitant vaccines according to the national schedules of the participating countries, but the effect, if any, of the concomitant administration on IPV immunogenicity will not be assessed. Optimum immunogenicity expected from the dose(s) of IPV in the post-eradication era will have to be balanced with the cost and supply constraints of IPV. This study will be critical to determine how many doses of IPV and which schedule are optimal for the post-eradication era after the global cessation of Oral Polio Vaccine (OPV) use.

Official Title
-----------------
A Phase 3, Open-label, Multicenter Randomized Trial to Evaluate Humoral Immunogenicity of Various Schedules of Intramuscular Full-Dose and Intradermal Fractional Dose of Inactivated Polio Vaccine in Latin American Infants

Conditions
-----------------
Poliomyelitis

Intervention / Treatment
-----------------
* Biological: IPV
* Biological: f-IPV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants of 6 weeks of age (-7 to + 7 days) on date of enrollment. Healthy, as assessed from medical history and physical examination by a study physician, Written informed consent obtained from parents or legal representatives who have been properly informed about the study and are able to comply with planned study procedures. Exclusion Criteria: Vaccinated with any poliovirus vaccine prior to inclusion, A household contact with OPV vaccination history in the past 4 weeks, HIV infection or pharmacologic immunosuppression, Known allergy to any component of the study vaccines (phenoxyethanol, formaldehyde), Uncontrolled coagulopathy or blood disorder contraindicating intramuscular and intradermal injections, Acute severe febrile illness on day of vaccination deemed by the Investigator(s) to be a contraindication for vaccination, Not suitable for inclusion or is unlikely to comply with the protocol in the opinion of the investigator(s).

Ages Eligible for Study
-----------------
Minimum Age: 5 Weeks
Maximum Age: 7 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>3 doses IPV IM at 10, 14 & 36 weeks of age incl. blood sampling at 10, 14, 18 & 40 weeks. | Biological: IPV<br>* Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)<br>|
| Experimental: Group B<br>2 doses IPV IM at 14 & 36 weeks of age incl. blood sampling at 14, 18, 36 & 40 weeks. | Biological: IPV<br>* Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)<br>|
| Experimental: Group C<br>3 doses f-IPV ID at 10, 14 & 36 weeks of age incl. blood sampling at 10, 14, 18 & 40 weeks. | Biological: f-IPV<br>* Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)<br>|
| Experimental: Group D<br>2 doses f-IPV ID at 14 & 36 weeks of age incl. blood sampling at 14, 18, 36 & 40 weeks. | Biological: f-IPV<br>* Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 2 Doses IPV IM | To determine if the seroconversion rate of a 2-dose intradermally administered fractional-dose inactivated poliovirus vaccine (f-IPV) regimen administered at 14 and 36 weeks of age is non-inferior to that of a 2-dose intramuscularly administered inactivated poliovirus vaccine (IPV) regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 
| Seroconversion Non-inferiority of 2 Doses IPV IM vs 3 Doses IPV IM | To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 
| Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 3 Doses f-IPV ID | To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion Superiority of 2 Doses IPV IM at Different Schedules | To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the second dose | 
| Seroconversion Superiority of 2 Dose f-IPV ID at Different Schedules | To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose f-IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the second dose | 
| Seroconversion Non-inferiority of 2 Dose f-IPV ID vs 3 Dose IPV IM | To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 
| Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 3 Doses IPV IM | To determine if the seroconversion rate of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen also administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 
| Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 2 Doses IPV IM | To determine if the seroconversion rate to a 3-dose regimen of f-IPV administered at 10, 14, and 36 weeks of age is non-inferior to that of a 2-dose IPV regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2. | To be assessed 4 weeks after the last dose | 
| Number of Participants Experiencing SAEs, IMEs and/or Severe Local Reactions | To assess the safety of each vaccine (IPV and f-IPV) as measured by the number of subjects experiencing serious adverse events (SAEs), important medical events (IMEs) and/or severe local reactions. This assessments is done in the Total Vaccinated Population (744 subjects). | 9 months |