Safety and Immunogenicity Study of a 13-valent Pneumococcal Polysaccharide Conjugate Vaccine

Study Overview
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Brief Summary
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This study is an open-label combined randomized double-blind, positive control phase Ⅰ clinical trial of the a 13-valent Pneumococcal Polysaccharide Conjugate Vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to preliminary evaluate the safety and immunogenicity of the study vaccine

Detailed Description
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This study is an open-label combined randomized double-blind, positive control phase Ⅰ clinical trial in subjects aged 2 months (minimum 6 weeks) and above. The experimental vaccine was manufactured by Sinovac Research & Development Co., Ltd. .And one of the positive control vaccine was manufactured by WALVAX Biotechnology Co., Ltd( WALVAX PCV13) ,the other manufactured by Pfizer(Pfizer PCV13).A total of 310 subjects including 20 adults aged 18-49 years,20 adolescents and children aged 6 7 years ,60 children aged 2-5 years,60 infants aged 12 23 months,60 infants aged 7  11 months,60 infants aged 2 months (minimum 6 weeks), and 30 infants aged 3 months will be enrolled.Subjects will be assigned to receive one dose , two doses ,three doses or four doses of experimental vaccine or different positive control vaccines . Subjects aged 18-49 years will receive one dose of experimental vaccine.Subjects aged 6 17 years will receive one dose of experimental vaccine.Subjects aged 2 5 years will be randomly divided into two groups in a ratio of 1:1,and each group will receive one dose of experimental vaccine or control vaccine(WALVAX PCV13）.Subjects aged 7   11 months and subjects aged 12  23 months will be randomly divided into two groups in a 1:1 ratio,the subjects aged 12   23 months will receive two doses of experimental vaccine or control vaccine on the schedule of month 0,2 .Subjects aged 7  11 months will receive 3 doses of experimental vaccine or control vaccine (WALVAX PCV13）on the immunization schedule of month 0,2,4.Subjects aged 3 months will receive 4 doses of experimental vaccine.Subjects aged 2 months will be randomly divided into 2 groups in a 1:1 ratio and each group will receive 4 doses of experimental vaccine or control vaccine (Pfizer PCV13).

Official Title
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An Open-label Combined Randomized Double-blind, Positive Control Clinical Trial in Subjects Aged 2 Months (Minimum 6 Weeks) and Above to Preliminary Evaluate the Safety and Immunogenicity of a 13-valent Pneumococcal Polysaccharide Conjugate Vaccine

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: Investigational 13-valent Pneumococcal Polysaccharide Conjugate Vaccine
* Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( WALVAX PCV13)
* Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( Pfizer PCV13)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants aged 2 months (minimum 6 weeks), healthy infants aged 3 months, healthy infants aged 7   11 months, healthy infants aged 12  23 months, healthy children aged 2  5 years, healthy adolescent and children aged 6  17 years, healthy adults aged 18  49 years； Proven legal identification and vaccination certificate (vaccination certificate is required for those aged 5 and below)； The subject and/or guardian can understand and voluntarily sign the informed consent form. Exclusion Criteria: Have received pneumococcal polysaccharide vaccine or pneumococcal polysaccharide conjugate vaccine; Have Bacterial pneumonia or invasive pneumococcal infectious disease (IPD) caused by pneumococcus confirmed by sputum culture; History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; Autoimmune disease or immunodeficiency / immunosuppression; Severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver or kidney diseases, malignant tumors, etc.; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; History of thyroidectomy, absence of spleen, functional absence of spleen, and absence of spleen or splenectomy due to any circumstance; Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation; 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.

Ages Eligible for Study
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Minimum Age: 6 Weeks
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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group of One Dose<br>110 Participants (including 20 subjects aged 18 49 years, 20 subjects aged 6 17 years , 30 subjects aged2-5 years) will receive one dose of experimental vaccine | Biological: Investigational 13-valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* The investigational vaccine was manufactured by Sinovac Research & Development Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and diphtheria CRM197 in 0·5 mL of aluminum phosphate ,sodium chloride,polysorbate 80 and succinic acid per injection.<br>|
| Experimental: Experimental Group of Two Doses<br>30 Participants aged 12 23 months will receive two doses of experimental vaccine on the schedule of month 0,2. | Biological: Investigational 13-valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* The investigational vaccine was manufactured by Sinovac Research & Development Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and diphtheria CRM197 in 0·5 mL of aluminum phosphate ,sodium chloride,polysorbate 80 and succinic acid per injection.<br>|
| Experimental: Experimental Group of Three Doses<br>30 Participants aged 7 11 months will receive two doses of experimental vaccine on the primary immunization schedule of month 0,2 and one dose of booster immunization during the participants aged 12 15 months . | Biological: Investigational 13-valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* The investigational vaccine was manufactured by Sinovac Research & Development Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and diphtheria CRM197 in 0·5 mL of aluminum phosphate ,sodium chloride,polysorbate 80 and succinic acid per injection.<br>|
| Experimental: Experimental Group of Four Doses<br>30 Participants aged 3 months will receive three doses of experimental vaccine on the primary immunization schedule of month 0,1,2 and one dose of booster immunization during the participants aged 12 15 months ; 30 Participants aged 2 months will receive three doses of experimental vaccine on the primary immunization schedule of month 0,2,4 and one dose of booster immunization during the participants aged 12 15 months | Biological: Investigational 13-valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* The investigational vaccine was manufactured by Sinovac Research & Development Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and diphtheria CRM197 in 0·5 mL of aluminum phosphate ,sodium chloride,polysorbate 80 and succinic acid per injection.<br>|
| Active Comparator: Control Group of One Dose With WALVAX PCV13<br>30 Participants aged 2-5 years will receive one dose of control vaccine (WALVAX PCV13) | Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( WALVAX PCV13)<br>* The control vaccine was manufactured by WALVAX Biotechnology Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and tetanus toxoid vector (TT) in 0·5 mL of aluminum phosphate ,disodium hydrogen phosphate and sodium dihydrogen phosphate per injection.<br>|
| Active Comparator: Control Group of Two Doses With WALVAX PCV13<br>30 Participants aged 12 23 months will receive two doses of control vaccine(WALVAX PCV13) on the schedule of month 0,2. | Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( WALVAX PCV13)<br>* The control vaccine was manufactured by WALVAX Biotechnology Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and tetanus toxoid vector (TT) in 0·5 mL of aluminum phosphate ,disodium hydrogen phosphate and sodium dihydrogen phosphate per injection.<br>|
| Active Comparator: Control Group of Three Doses With WALVAX PCV13<br>30 Participants aged 7 11 months will receive two doses of control vaccine(WALVAX PCV13) on the primary immunization schedule of month 0,2 and one dose of booster immunization during the participants aged 12 15 months . | Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( WALVAX PCV13)<br>* The control vaccine was manufactured by WALVAX Biotechnology Co., Ltd. each for purified 13 serotypes of pneumococcal polysaccharide and tetanus toxoid vector (TT) in 0·5 mL of aluminum phosphate ,disodium hydrogen phosphate and sodium dihydrogen phosphate per injection.<br>|
| Active Comparator: Control Group of Three Doses With Pfizer PCV13<br>30 Participants aged 2 months will receive three doses of control vaccine(Pfizer PCV13 on the primary immunization schedule of month 0,2,4 and one dose of booster immunization during the participants aged 12 15 months | Biological: Control 13-valent Pneumococcal Polysaccharide Conjugate Vaccine ( Pfizer PCV13)<br>* The control vaccine was manufactured by Pfizer. each for purified 13 serotypes of pneumococcal polysaccharide and tetanus toxoid vector (TT) in 0·5 mL of aluminum phosphate ,sodium chloride ,succinic acid ,polysorbate 80 and water for injection 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 0 to 30 days after each dose of experimental vaccine | Day 0-30 after each dose of experimental vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index-incidence of adverse reactions | Incidence of adverse reactions 0 to 7 days after each dose of experimental vaccine | Day 0-7 after each dose of experimental vaccine | 
| Safety index-incidence of abnormal indicators | Incidence of abnormal indicators of Blood routine, blood biochemistry and urine routine 3 days after vaccination in subjects aged 2 years and older | Day 3 after vaccination after each dose of experimental vaccine | 
| Safety index-Incidence of serious adverse events during the safety observation period | Incidence of serious adverse events during the safety observation period, including 1 month after vaccination in subject aged 6 years and older, and 6 months after primary immunization and 1 month after booster immunization in subject aged 2 months (minimum 6 weeks) to 5 years(if any) | 1 month after vaccination ,6 months after primary immunization or 1 month after booster immunization | 
| Immunogenicity index-Geometric mean concentrations (GMC) and GMI of specific IgG for each serotype | Geometric mean concentrations (GMC) and GMI of specific IgG for each serotype at 30 days after vaccination in subjects of all age groups | Day 30 after vaccination | 
| Immunogenicity index-Geometric mean titers (GMT) and GMI of serotype specific opsonophagocytic antibody OPA for each serotype | Geometric mean titers (GMT) and GMI of serotype specific opsonophagocytic antibody OPA for each serotype at 30 days after vaccination in subjects of all age groups | Day 30 after vaccination | 
| Immunogenicity index-Seropositive rates，GMCs and GMI of serum specific antibody | Seropositive rates of IgG concentration ≥0.35μg/mL, ≥1.0μg/mL, geometric mean concentration (GMCs) and GMI of serum specific antibody at 30 days after primary immunization in subjects of all age groups | Day 30 after vaccination | 
| Immunogenicity index-Proportion of OPA ≥1:8 of each serum and geometric mean titer (GMT) | Proportion of OPA ≥1:8 of each serum and geometric mean titer (GMT)in subjects of all age groups at 30 days after primary immunization | Day 30 after vaccination | 
| Immunogenicity index-Seropositive rates of IgG concentration ≥0.35μg/mL, ≥1.0μg/mL, geometric mean concentration (GMC) | Seropositive rates of IgG concentration ≥0.35μg/mL, ≥1.0μg/mL, geometric mean concentration (GMC) in subjects aged 2 months (Minimum 6 weeks), 3 months and 7   11 months at 30 days before and after booster immunization | Day 30 before and after booster immunization | 
| Immunogenicity index-Proportion of OPA ≥1:8 for each serotype and geometric mean titer (GMT) | Proportion of OPA ≥1:8 for each serotype and geometric mean titer (GMT) in subjects aged 2 months (Minimum 6 weeks), 3 months, and 7  11 months at 30 days before and after booster immunization | Day 30 before and after booster immunization |