Studies of the Safety and Immunogenicity of a Sabin Inactivated Poliovirus Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of sIPVs of different dosages in adults, children and infants in a phase I open-label study, and then assess its immunogenicity and safety in healthy infants between 60 and 90 days old in a phase II blind, randomized, and controlled study.

Detailed Description
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This study is a combination of phases I and II. Phase I study is open-label, and only collect safety information of the investigational sIPVs in adults, children and infants. Phase II study is double-blind, randomized, controlled study of the immunogenicity and safety of the investigational vaccines and two other commercialized inactivated poliovirus vaccines in healthy infants.

Official Title
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A Open-label Phase I Study to Evaluate Safety of a Sabin Inactivated Poliovirus Vaccine (sIPV) in Adults, Children, and Infants, and a Blinded, Randomized and Controlled Phase II to Evaluate Safety and Immunogenicity of it in Infants

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: Single-dose regimen of high dosage investigational sIPV
* Biological: Single-dose regimen of medium dosage investigational sIPV
* Biological: Three-dose regimen of high dosage investigational sIPV
* Biological: Three-dose regimen of medium dosage investigational sIPV
* Biological: Three-dose regimen of low dosage investigational sIPV
* Biological: Three-dose regimen of commercialized sIPV
* Biological: Three-dose regimen of commercialized IPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer between 60-90 days old, 6-12 years old, or 18-49 years old; Healthy volunteers who fulfill all the required conditions for receiving the investigational vaccine as established by medical history and clinical examination and determined by investigators; Proven legal identity; Participants (≥ 18 years old), or guardians of the participants (< 18 years old) should be capable of understanding the written consent form, and such form should be signed prior to enrolment; Complying with the requirement of the study protocol; Axillary temperature ≤ 37.0 °C; Exclusion Criteria: Breast feeding, pregnant, or expected to conceive in the next 60 days; History of allergy to any vaccine, or any ingredient of the vaccine, or serious adverse reaction(s) to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc; Congenital malformation, developmental disorders, genetic defects, or severe malnutrition; Autoimmune disease or immunodeficiency/immunosuppressive; serious chronic diseases, serious cardiovascular disease, hypertension or diabetes that cannot be stabilized by medication, liver or kidney disease, malignancy, etc; severe nervous system disease (epilepsy, seizures or convulsions) or mental illness; History of thyroidectomy, asplenia, functional asplenia, or any condition resulting in the absence or removal the spleen; Bleeding disorder diagnosed by a doctor (e.g., coagulation factor deficiency, coagulation disorder, or platelet disorder) , or significant bruising or coagulopathy; Long term history of alcoholism or drug abuse; Receipt of any of the following products: Any subunit or inactivated vaccine within the past 7 day; Any live attenuated vaccine within the past 14 days; Any other investigational medicine(s) within the past 30 days; Any blood product within the past 3 months; Any immunosuppressant, cytotoxic medications, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) within the past 6 month prior to study entry; Acute illness or acute exacerbation of chronic disease within the past 7 days; Axillary temperature > 37.0 °C; Infant participants with prior vaccination of poliovirus; Any other factor that, in the judgment of the investigator, suggesting the volunteer is unsuitable for this study;

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 49 Years

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I Adult Group - High dosage<br>Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0; Intervention: Single-dose regimen of high dosage investigational sIPV | Biological: Single-dose regimen of high dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Adult Group - Medium dosage<br>Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0; Intervention: Single-dose regimen of medium dosage investigational sIPV | Biological: Single-dose regimen of medium dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Child Group - High dosage<br>Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0; Intervention: Single-dose regimen of high dosage investigational sIPV | Biological: Single-dose regimen of high dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Child Group - Medium dosage<br>Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0; Intervention: Single-dose regimen of medium dosage investigational sIPV | Biological: Single-dose regimen of medium dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Infant Group - High dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of high dosage investigational sIPV | Biological: Three-dose regimen of high dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Infant Group - Medium dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of medium dosage investigational sIPV | Biological: Three-dose regimen of medium dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: Phase I Infant Group - Low dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of low dosage investigational sIPV | Biological: Three-dose regimen of low dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: PhaseⅡExperimental Group - High dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of high dosage investigational sIPV | Biological: Three-dose regimen of high dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: PhaseⅡExperimental Group - Medium dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of medium dosage investigational sIPV | Biological: Three-dose regimen of medium dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Experimental: PhaseⅡExperimental Group - Low dosage<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of low dosage investigational sIPV | Biological: Three-dose regimen of low dosage investigational sIPV<br>* The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..<br>|
| Active Comparator: PhaseⅡControl Group -commercialized sIPV<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention:Three-dose regimen of commercialized sIPV | Biological: Three-dose regimen of commercialized sIPV<br>* The control vaccine was manufactured by Chinese Academy of Medical Sciences.<br>|
| Active Comparator: PhaseⅡ Control Group -commercialized IPV<br>Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively; Intervention: Three-dose regimen of commercialized IPV | Biological: Three-dose regimen of commercialized IPV<br>* The control vaccine was manufactured by Sanofi Pasteur S.A (IMOVAX POLIO).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seroconversion rates (SCRs) of each group of the phase II trial after three-dose regimen | Subjects whose pre-immune antibody level < 1:8 and post-immune antibody level ≥ 1:8, or those whose pre-immune antibody level ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted. | 90 days | 
| The post-immune geometric mean titer (GMT) of each group of the phase II trial after three-dose regimen | GMT of each group of the phase II trial 30 days after three-dose regimen which lasts 60 days. | 90 days | 
| The geometric mean fold increase (GMI) of each group after three-dose regimen | The GMI is the increase of post-immune GMT from pre-immune GMT. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidences of solicited adverse events (AEs) of each group in both phase I and II trials | Solicited AEs occurred within 7 days after each injection will be collected. | 7 days | 
| The incidences of unsolicited adverse events (AEs) of each group in both phase I and II trials | Unsolicited AEs occurred within 30 days after each injection will be collected. | 30 days | 
| The incidences of serious adverse events (SAEs) of each group in both phase I and II trials | SAEs occurred within 30 days after each injection will be collected. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sabin strain, Inactivated poliovirus vaccine, poliomyelitis, safety, immunogenicity, infant