Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine in 2, 4, 6 Months of Age

Study Overview
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Brief Summary
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The trial is a phase III, non-inferiority, observer-blind, randomised, active controlled, multicentre clinical trial with 2 parallel groups: IPV-Al SSI (investigational vaccine) and IPV SSI (comparator vaccine). The vaccines will be administered at 2, 4 and 6 months of age.

Detailed Description
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In addition to the trial vaccines (IPV-Al SSI or IPV SSI), the trial subjects will receive concomitant childhood vaccinations during the trial period. The trial vaccine (IPV-Al SSI or IPV SSI) is administered in the RIGHT thigh, whereas the other injectable childhood vaccines are administered in the opposite (LEFT) thigh. At Visit 1 (inclusion, screening, blood sample, randomisation and 1st vaccination), written informed consent is obtained and the subject's eligibility is assessed according to the pre-specified in-/exclusion criteria. Information on medical history, demographics and concomitant medication are collected and a physical examination is performed and vital signs are measured. A prevaccination blood sample is taken for polio antibody determinations and the subject is randomly allocated into one of the two vaccination groups and vaccinated. A subset of 200 subjects are randomly chosen to have an extra blood sample taken at Visit 3. The subject is observed for immediate AEs 30 minutes after all vaccinations. An eDiary, thermometer and ruler are handed out to the parents for measurements of temperature and recording of injection site reactions and solicited systemic AEs. These activities are performed daily, starting on the day of the vaccination and the following 2 days and until resolved, and for recording of any other AEs as instructed by the trial staff. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary. At Visit 2 (2nd vaccination), 2 months after Visit 1, the eDiary is collected and AEs and concomitant medications are recorded. Contraindications are reviewed, the 2nd vaccination is administered, immediate reactions are observed and the eDiary is returned to the partents for recordings of AEs and concomitant medications. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary. At Visit 3 (3rd vaccination), 2 months after Visit 2, the eDiary is collected and AEs and concomitant medication are recorded. A blood sample from a subset of the subjects is taken for polio antibody determinations. Contraindications are reviewed, the 3rd vaccination is given, immediate reactions are observed and the eDiary is returned to the parents. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary. At Visit 4 (blood sample and trial completion), 1 month after Visit 3, the eDiary is collected and AEs and concomitant medications are recorded and a blood sample for polio antibody determination is taken. A safety follow-up telephone call will be conducted at 12 months of age.

Official Title
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Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine, IPV-Al SSI, in Comparison to Non-adjuvanted Full Dose IPV SSI, in Infants Vaccinated at 2, 4 and 6 Months of Age

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: IPV-Al SSI
* Biological: IPV SSI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants 2 months of age (54-75 days of age) on date of first vaccination Healthy assessed from medical history and physical examination Parent(s)/guardian(s) have been properly informed about the trial and signed informed consent form Parent(s)/guardian(s)granted access to the infant's trial related medical records Parent(s)/guardian(s)are likely to comply with trial procedures Exclusion Criteria: Vaccinated with any polio vaccine other than the trial vaccines, prior to inclusion or planned during the trial OPV vaccination or known exposure to poliovirus (wild or vaccine-derived) in household (living together) within 3 months prior to inclusion or planned during the trial Low birth weight (< 2,500 g) Known or suspected immunodeficiency (e.g. leukaemia, lymphoma) or family history of congenital or hereditary immunodeficiency. HIV infection is not an exclusion criteria Severe uncontrolled chronic (e.g. neurologic, pulmonary, gastrointestinal, hepatic, renal or endocrine) disease Known or suspected allergy to vaccine constituents (e.g. hypersensitivity to formaldehyde, aluminium or 2-phenoxyethanol) Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections or blood sampling Treatment with a product which is likely to modify the immune response (e.g. systemic corticosteroids, blood products and immunoglobulins) prior to inclusion or planned during the trial period Participating in another clinical trial Not suitable for inclusion in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 54 Days
Maximum Age: 75 Days

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPV-Al SSI<br>IPV-Al contains the reduced dose of IPV to be administered intramuscularly to the anterolateral of the right thigh. Each subject randomised to this group will receive a total of three primary injections - one at 2 months, 4 months and 6 months of age. | Biological: IPV-Al SSI<br>* Total of three primary injections of IPV-Al SSI, one at 2, 4 and 6 months of age<br>|
| Active Comparator: IPV SSI<br>IPV SSI contains the full dose of IPV to be administered intramuscularly to the anterolateral of the right thigh. Each subject randomised to this group will receive a total of three primary injections - one at 2 months, 4 months and 6 months of age. | Biological: IPV SSI<br>* Total of three primary injections of IPV SSI, one at 2, 4 and 6 months of age<br>* Other names: IPV Vaccine SSI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion for poliovirus type 1, 2 and 3 for IPV-Al compared to IPV SSI in infants |  | Change from baseline to one month after 3rd vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events following vaccinations (key secondary) |  | After primary injections at 2, 4 and 6 months of age | 
| Subjects with seroprotection against poliovirus types 1, 2 and 3 |  | One months after 3rd vaccination | 
| Subjects with poliovirus types 1, 2 and 3 post-vaccination titres >= 4-fold above estimated titre of maternal antibody |  | One months after 3rd vaccination | 
| Geometric mean titres (GMTs) and median titers for poliovirus types 1, 2 and 3 |  | One months after 3rd vaccination | 
| Reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3 |  | From baseline and one months after 3rd vaccination |