Safety of Sabin Inactivated Poliovirus Vaccine in Adults, Children and Infants and Lot Consistency Immunogenicity, and Safety of the msIPV in 2 Months Old Infants

Study Overview
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Brief Summary
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This study includes two parts.A clinical trial with a open-label to evaluate the safety of Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml/dose)(hereinafter referred to as msIPV)manufactured by Sinovac Biotech Co., Ltd. in adults, children and infants in partⅠ and a blinded,randomized and controlled clinical trial to evaluate the lot consistency immunogenicity, and safety of the msIPV in 2 months old infants in partⅡ.

Detailed Description
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This study includes two stages.A clinical trial with a open-label to evaluate the safety of Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml/dose)(hereinafter referred to as msIPV) in adults, children and infants in stageⅠ and a blinded,randomized and controlled clinical trial to evaluate the lot consistency immunogenicity, and safety of the msIPV in 2 months old infants in stageⅡ. A total of 1572 subjects including 24 adults aged 18-49 years,24 children aged 4 years,1524 infants aged 2 months will be enrolled. StagesⅠ:72 healthy subjects, including 24 adults,24 children and 24 infants will be enrolled. 24 adults and 24 children will receive one dose of vaccine and 24 infants will receive 4 doses of vaccine according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. StagesⅡ:1500 infants aged 2 months will be randomly divided into 5 groups(Experimental Vaccine-lot 1, Experimental Vaccine-lot 2, Experimental Vaccine-lot 3,IPV control group and single-person sIPV control group) according to the ratio of 1:1:1:1:1. Subjects in 3 experimental groups will receive 5-person sIPV produced by Sinovac for three lots,subjects in IPV control group will receive IPV produced by Pasteur, and subjects in single-person sIPV control group will receive single-person sIPV produced by Sinovac.All subjects will received 4 doses of experimental or control vaccine according to the primary immunization schedule of 0,1,2 months, one dose of booster at 18 months of age.

Official Title
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A Clinical Trial With a Open-label Phase to Evaluate the Safety of 5-person Sabin Inactivated Poliovirus Vaccine (Vero Cell)（ msIPV） in Adults, Children and Infants, and a Blinded,Randomized and Controlled Phase to Evaluate the Lot Consistency Immunogenicity, and Safety of the msIPV in 2 Months Old Infants

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: Experimental vaccine
* Biological: IPV control vaccine
* Biological: single-person sIPV control vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for adult subjects : Healthy adults aged 18-49 days; Proven legal identification; The subject can understand and voluntarily sign the informed consent form. Inclusion criteria for children subjects : Healthy children aged 4 years old; Subjects who have completed primary immunization with 3 doses of sIPV vaccine; Proven legal identification and vaccination certificate; The subject and/or guardian can understand and voluntarily sign the informed consent form. Inclusion criteria for infant subjects: Healthy infants aged 2 months (60 89 days) Proven legal identification and vaccination certificate; The subject and/or guardian can understand and voluntarily sign the informed consent form. Exclusion Criteria: Exclusion criteria for adult subjects: Women aged 18 to 49 years, positive urine pregnancy test, pregnant women, breastfeeding women, or planning to become pregnant within 3 months; Previous history of vaccination of sIPV vaccine; Allergy history, history of asthma, including allergy history to vaccine or vaccine components, serious adverse reactions to the vaccine, such as urticaria, dyspnea, angioneurotic edema or stomachache, etc; Congenital malformation or developmental disorder, genetic defect, serious malnutrition, etc.; Autoimmune disease or immunodeficiency/immunosuppression; Thyroid disease or thyroidectomy history, absence of spleen, functional absence of spleen, and any conditions resulting in absence of spleen or splenectomy; Serious chronic diseases, serious cardiovascular diseases, hypertension that cannot be controlled by drugs (systolic blood pressure > 140mmHg, diastolic blood pressure > 90mmHg), diabetes, liver and kidney diseases, malignant tumors, etc; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Medical diagnosis of coagulation abnormalities (such as coagulation factor deficiency, coagulation disorders, platelet abnormalities) or marked bruising or coagulation disorders; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids(excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months; History of alcohol or drug abuse; Receipt of blood products within in the past 3 months; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Receipt of inactivated or subunit vaccines in the past 7 days; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial. Exclusion criteria for children subjects: Have received 4 doses of sIPV vaccine; History of polio; Allergy history, history of asthma, including allergy history to vaccine or vaccine components, serious adverse reactions to the vaccine, such as urticaria, dyspnea, angioneurotic edema or stomachache, etc; Congenital malformation or developmental disorder, genetic defect, serious malnutrition, etc.; Autoimmune disease or immunodeficiency/immunosuppression; Thyroid disease or thyroidectomy history, absence of spleen, functional absence of spleen, and any conditions resulting in absence of spleen or splenectomy; Suffering from serious cardiovascular diseases, diabetes, liver and kidney diseases, malignant tumors, etc; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Medical diagnosis of coagulation abnormalities (such as coagulation factor deficiency, coagulation disorders, platelet abnormalities) or marked bruising or coagulation disorders; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids(excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months; History of alcohol or drug abuse; Receipt of blood products within in the past 3 months; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Receipt of inactivated or subunit vaccines in the past 7 days; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial. Exclusion criteria for infant subjects: Previous history of vaccination of sIPV vaccine; History of polio; Allergy history, history of asthma, including allergy history to vaccine or vaccine components, serious adverse reactions to the vaccine, such as urticaria, dyspnea, angioneurotic edema or stomachache, etc; Preterm birth babies (delivered before 37 weeks gestation), low birth weight (girls with birth weight <2300g, boy with birth weight<2500 g); History of dystocia, asphyxia and nervous system damage at birth; Congenital malformation or developmental disorder, genetic defect, serious malnutrition, etc.; Autoimmune disease or immunodeficiency/immunosuppression; Thyroid disease or thyroidectomy history, absence of spleen, functional absence of spleen, and any conditions resulting in absence of spleen or splenectomy; -Suffering from serious cardiovascular diseases, diabetes, liver and kidney diseases, malignant tumors, etc; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Medical diagnosis of coagulation abnormalities (such as coagulation factor deficiency, coagulation disorders, platelet abnormalities) or marked bruising or coagulation disorders; Have received immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids(excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy); Receipt of blood products ; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Receipt of inactivated or subunit vaccines in the past 7 days; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial.

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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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety group in adults<br>24 adults will receive one dose of 5-person sIPV vaccine to evaluate the safety of msIPV vaccine. | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Experimental: Safety group in children<br>24 children will receive one dose of 5-person sIPV vaccine to evaluate the safety of msIPV vaccine. | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Experimental: Safety group in infants<br>24 infants will receive 4 doses of vaccine according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months to evaluate the safety of msIPV vaccine . | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Experimental: Experimental Vaccine-lot 1<br>300 infants will receive 4 doses of 5-person sIPV vaccine of commercial scale lot 1 according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Experimental: Experimental Vaccine-lot 2<br>300 infants will receive 4 doses of 5-person sIPV vaccine of commercial scale lot 2 according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Experimental: Experimental Vaccine-lot 3<br>300 infants will receive 4 doses of 5-person sIPV vaccine of commercial scale lot 3 according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. | Biological: Experimental vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (2.5ml)-investigational vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen (per 0.5ml): type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 2.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate,2 - phenoxyethanol for per injection.<br>* Other names: msIPV;|
| Active Comparator: IPV control group<br>300 infants will receive 4 doses of IPV vaccine produced by Pasteur according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. | Biological: IPV control vaccine<br>* Inactivated Poliovirus Vaccine - control vaccine produced by Sanofi. Inactivated poliovirus antigens: Mahoney strain for type 1 (40DU), MEF-1 strain for type 2 (8DU), Saukett strains for type 3 (32DU) in 0.5 ml mixture of 2- phenoxyethanol,ethanol,formaldehyde,hanks199 medium (containing amino acids, mineral salts, vitamins, glucose, polysorbate 80 and water for injection),hydrochloric acid or sodium hydroxide (for pH value adjustment),trace amounts of antibiotics (neomycin, streptomycin and polymyxin B)for per injection.<br>|
| Active Comparator: single-person sIPV control group<br>300 infants will receive 4 doses of single-dose sIPV vaccine produced by Pasteur according to the primary immunization schedule of 0,1,2 months and booster immunization schedule of 18 months. | Biological: single-person sIPV control vaccine<br>* Sabin Inactivated Poliovirus Vaccine (Vero cell) (0.5ml) -control vaccine produced by Sinovac Biotech Co., Ltd. Inactivated Sabin poliovirus antigen: type 1 (15DU), type 2 (45DU), and type 3 (45DU)in 0.5 ml mixture of medium 199,glycine,formaldehyde,sodium chloride,potassium chloride,calcium chloride,magnesium sulfate,disodium phosphate,sodium dihydrogen phosphate for per injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-incidence of adverse reactions | Incidence of adverse reactions within 30 days after each dose | Within 30 days after each dose | 
| Immunogenicity index-Geometric mean titers (GMT) | GMT 30 days after primary immunization in msIPV vaccination group | 30 days after primary immunization | 
| Immunogenicity index- seroconversion rate of neutralizing antibody | Seroconversion rate of neutralizing antibody 30 days after primary immunization in combined experiment group and IPV control group | 30 days after primary immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-incidence of adverse reactions | Incidence of adverse reactions within 7 days after each dose | Within 7 days after each dose | 
| Safety index-the incidence of adverse reactions | Incidence of SAE during the period of safety monitoring | During the period of safety monitoring | 
| Immunogenicity index- Neutralizing antibody positive rate and GMI | Neutralizing antibody positive rate and GMI and percentage of subjects with antibody ≥1:64 30 days after primary immunization | 30 days after primary immunization | 
| Immunogenicity index- Neutralizing antibody positive rate | Neutralizing antibody positive rate, percentage of subjects with antibody ≥1:64 and GMT before booster dose | Before booster dose | 
| Immunogenicity index-Neutralizing antibody positive rate,GMT and GMI | Neutralizing antibody positive rate, percentage of subjects with antibody ≥1:64, GMT and GMI 30 days after booster dose | 30 days after booster dose |