Comparison of Immunogenicity of Inactivated Poliovirus Vaccine (IPV) Administered Intramuscularly or Intradermally

Study Overview
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Brief Summary
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Polio is an acute transmissible disease caused by any of the three polio virus serotypes (types 1, 2 or 3). In Mozambique, polio vaccination is part of the immunization schedule of the expanded vaccination program. The oral vaccine (OPV) is administered at months 0,2,3, and 4 and a single dose of the inactivated poliovirus vaccine (IPV) is given intramuscularly at month 4. In 2016 shortage of IPV supply caused stock-outs and put strain on IPV use for routine immunizations as well as for poliovirus outbreak response. Therefore, assessment of new vaccine regimens using smaller doses of IPV are needed. Administration of fractionated IPV (fIPV), i.e., 1/5 (0.1mL) of the standard dose, intradermally has shown to be safe and to provide an immune response similar to the standard dose of IPV that is currently given intramuscularly. However, intradermal administration of fIPV is technically difficult and many countries are hesitant to adopt fIPV in their routine immunization schedules. Therefore, the investigators need data confirming that the use of the fIPV vaccine intramuscularly is safe and the immune response is not inferior to the use of fIPV intradermally. Study Objective: to compare the immunogenicity of fIPV administered intramuscularly or intradermally in infants at 2 and 4 months of age. Study Hypotheses: the seroconversion rate after administration of one or two doses of fIPV intramuscularly is not inferior to the fIPV intradermally. The priming effect after fIPV administered intramuscularly is not inferior to the fIPV intradermally. Study Methods: This will be a phase II non-inferiority clinical trial. 360 children will be enrolled in two study groups, with prior consent of the parents / guardians. In group I, 180 children will receive 0.1 ml of IPV intramuscularly and in group II 180 children will receive the same dose intradermally. There will not be a group control. The children will be selected at birth at pre-defined health units in Maputo city. The fractional IPV vaccine will be given to children at 2 and 4 months of age during routine vaccinations. In total there will be four study visits, of which the first two are vaccination visits. All visits will be performed at the health units. 1 ml of blood will be collected at each study visit to assess the immune response before and after vaccination. Data will be collected by trained and qualified personnel and in accordance with Good Clinical Practice standards. Adverse events following administration of the vaccine will be monitored and all serious adverse events will be reported to ethics and regulatory committees, and to World Health Organization (WHO). Evaluation of the immune response: Seroconversion rates and priming effect will be evaluated. Serum will be tested for the presence of neutralizing antibodies against poliovirus using standard neutralization assays and immunogenicity will be assessed by titration of anti-polio 2 immunoglobulin G.

Official Title
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Clinical Trial to Compare the Immunogenicity of the Inactivated Poliovirus Vaccine (IPV) Administered in Reduced Doses Intramuscularly or Intradermally in Infants at 2 and 4 Months of Age in the Maputo City

Conditions
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Polio

Intervention / Treatment
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* Biological: Inactivated poliovirus vaccine in reduced doses


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children whose parents/guardians consent to their participation; Children whose parents/guardians live in the study area and do not intend to depart during the study period. Exclusion Criteria: Children whose parents are under the legal age with exception of 16-years-old parents who are already living in marital status; Children whose parents have mental illness; Children with immunosuppression.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 2 Months

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 |
| --- | --- |
| Active Comparator: fIPV Intramuscular<br>180 children will receive 0,1 ml of inactivated poliovirus vaccine intramuscularly | Biological: Inactivated poliovirus vaccine in reduced doses<br>* contains the following excipients: 2-phenoxyethanol (2.5 mg), water for injection and diluent solution and phosphate buffer having the following composition: sodium phosphate, sodium chloride, potassium chloride, magnesium sulfate, phenol red and calcium chloride. dosage:0,1ml duration: first dose: month 2 of age; second dose: month 4 of age<br>|
| Active Comparator: fIPV Intradermal<br>180 children will receive 0,1ml of inactivated poliovirus vaccine intradermally | Biological: Inactivated poliovirus vaccine in reduced doses<br>* contains the following excipients: 2-phenoxyethanol (2.5 mg), water for injection and diluent solution and phosphate buffer having the following composition: sodium phosphate, sodium chloride, potassium chloride, magnesium sulfate, phenol red and calcium chloride. dosage:0,1ml duration: first dose: month 2 of age; second dose: month 4 of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion | Difference in seroconversion between arms as expressed by proportion of seropositive children on final blood collection. | month 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Priming | Difference in priming between arms as expressed by proportion of seropositive children on third blood collection among seronegative children at 2nd bleed | month 4+1week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Polio Virus