Safety and Immunogenicity of a New Inactivated Poliovirus Vaccine in Infants

Study Overview
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Brief Summary
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A new inactivated polio vaccine based on attenuated poliovirus strains was developed to transfer the technology to manufacturers in low- and middle-income countries. This vaccine was produced in different dosages and in different formulations. In healthy adults the safety of the highest dose was comparable to that of the existing inactivated polio vaccine. The purpose of this trial is to determine the safety of the different dosages and formulations of the vaccine in infants. The second goal of this study is to analyse the immune response after three doses in infants.

Detailed Description
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The goal of this study is to assess the safety and immunogenicity of Sabin-IPV and adjuvanted Sabin-IPV produced with the production process set up for technology transfer by the National Institute for Public Health and the Environment (RIVM, formerly the Netherlands Vaccine Institute (NVI). The primary objective is to evaluate safety (local and systemic reactions) of intramuscular injection with Sabin-IPV and adjuvanted Sabin-IPV in healthy infants. The secondary objective is to evaluate immunogenicity of three doses Sabin-IPV and adjuvanted Sabin-IPV in infants.

Official Title
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Double Blind Dose - Escalation, Randomized, Controlled, Phase I-II Trial to Evaluate Safety and Immunogenicity of Three Doses of Sabin-IPV and Adjuvanted Sabin-IPV in Healthy Infants

Conditions
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Poliomyelitis

Intervention / Treatment
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* Drug: IPV
* Drug: Low dose Sabin-IPV
* Drug: Low dose adjuvanted Sabin-IPV
* Drug: Middle dose Sabin-IPV
* Drug: Middle dose adjuvanted Sabin-IPV
* Drug: High dose Sabin-IPV
* Drug: High dose adjuvanted Sabin-IPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 8 weeks (56-63 days) at the time of first vaccination Infants in good general health, eligible to be vaccinated according to the Polish national vaccination program. The same health criteria apply as used in well-baby clinics when a child receives a vaccination, e.g. also children with a small increase in temperature (< 38.5° C) or with a common cold (runny nose etc) are seen as children with normal health. The parent(s)/legally representative(s) have to be willing and able to allow their child to participate in the trial according to the described procedures Presence of a signed informed consent in which the parent(s)/legally representative(s) have given written informed consent after receiving oral and written information (signature from one parent in case of single-parent family). Exclusion Criteria: Any IPV or OPV dose Known or suspected allergy against any of the vaccine components History of unusual or severe reactions to any previous vaccination administration of plasma (including immunoglobulins) or blood products prior and during the study Any vaccination less than 14 days before or after each vaccination with the IMP History of any neurological disorder including epilepsy or febrile seizures Any infectious disease at the time of screening and/or inclusion that might interfere with the results of the study Present evidence of serious disease(s) demanding immunosuppressive medical treatment, like cytostatics and prednisolones, that might interfere with the results of the study Any known or suspected primary or secondary immunodeficiency Communication problems interfering in the study realization according to the judgment of the investigator Bleeding disorders and use of anticoagulants Premature birth (<37 weeks) Participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 56 Days
Maximum Age: 63 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 5, 8, 16 D-antigen units respectively of Sabin-1,-2 and -3 per dose. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: Low dose Sabin-IPV<br> <br> |
| Experimental: Low dose adjuvanted Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 2.5, 4, 8 D-antigen units respectively of Sabin-1,-2 and -3 per dose adjuvanted with 0.5 mg aluminium hydroxide. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: Low dose adjuvanted Sabin-IPV<br> <br> |
| Experimental: Middle dose Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 10, 16, 32 D-antigen units respectively of Sabin-1,-2 and -3 per dose. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: Middle dose Sabin-IPV<br> <br> |
| Experimental: Middle dose adjuvanted Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 5, 8, 16 D-antigen units respectively of Sabin-1,-2 and -3 per dose adjuvanted with 0.5 mg aluminium hydroxide. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: Middle dose adjuvanted Sabin-IPV<br> <br> |
| Experimental: High dose Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 20, 32, 64 D-antigen units respectively of Sabin-1,-2 and -3 per dose. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: High dose Sabin-IPV<br> <br> |
| Experimental: High dose adjuvanted Sabin-IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 10, 16, 32 D-antigen units respectively of Sabin-1,-2 and -3 per dose adjuvanted with 0.5 mg aluminium hydroxide. Infants receive three vaccinations with an interval of 8 weeks between doses. | Drug: High dose adjuvanted Sabin-IPV<br> <br> |
| Active Comparator: Conventional IPV<br>Intramuscular injection of 0.5 ml of Inactivated Poliomyelitis Vaccine containing 40, 8, and 32 D-antigen units respectively of Mahoney, MEF-1 and Saukett poliovirus per dose. Infants receive three injections with an interval of 8 weeks between doses. | Drug: IPV<br> <br> * Other names: Inactivated polio vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse reactions following vaccination |  | 5 days or until adverse reactions have resolved | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of virus neutralizing titers in serum |  | 28 days after last vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sabin strains, Vaccination, Inactivated poliomyelitis vaccine, poliomyelitis