Phase III Clinical Trial of a Candidate PCV13 in Healthy People Aged 6 Weeks and Above (PICTPCV13i)

Study Overview
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Brief Summary
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Streptococcus pneumoniae is a major cause of morbidity and mortality in children worldwide, resulting in up to 1 million pediatric deaths every year.Since the licensure of PCV7 and PCV13,the reported overall decline in invasive pneumococcal disease in hospitalized children younger than 5 years several years is approximately 60% in Western countries.This is a single center,blind, randomized, positive-controlled clinical trial.The purpose of this study is to preliminary evaluate the safety of PCV13i vaccine in subjects at age of 7 months and above,and to investigate the safety and immunogenicity of PCV13i vaccine at age of 2 and 3 months,compared to PCV13.

Official Title
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A Randomized,Blind, Positive-controlled Phase III Clinical Trial to Evaluate the Safety and Immunogencity of 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT） in Healthy People Aged 6 Weeks and Above

Conditions
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Pneumococcal Infections, Streptococcal Infections, Bacterial Infections

Intervention / Treatment
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* Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）
* Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects of 2 months (minimum 6 weeks), 3 months , 7 months and above; Willing to provide proof of identity; Without vaccination history of pneumococcal vaccine; None-pregnancy or do not plan to pregnancy recently;; Volunteers of 18 years old and above who have the ability to understand clinical studie progress and sign informed consent; Volunteers of 8-17 years old and their guardians who willing sign informed consent; Able to understand and sign the informed consent by their guardians or trustees for the volunteers of 8 years old and below; Able and willing comply with the requirements of the protocol Exclusion Criteria: Volunteers whose axillary body temperature was >37.0# before vaccination Volunteers who suffered from Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc; Volunteers who has a history of epilepsy, convulsions or psychosis; Allergic person; Any prior administration of blood products in last 3 month; Any prior administration of other research medicines in last 1 month; Plans to participate in or is participating in any other drug clinical study; Any prior administration of attenuated live vaccine in last 14 days; Any prior administration of subunit or inactivated vaccines in last 7 days; Had fever before vaccination, Volunteers with temperature >37.0°C on axillary setting; According to the investigator's judgement, the subjects have any other factors that make them unfit to enroll the clinical trial

Ages Eligible for Study
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Minimum Age: 6 Weeks

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: 1A<br>Subjects received four doses of PCV13i at 2 months of age (At least 6 weeks old) | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular<br>* Other names: PCV13i;|
| Active Comparator: 1B<br>Subjects received four doses of PCV13 at 2 months of age (At least 6 weeks old) | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* 0.5mL,Intramuscular<br>* Other names: Prevnar;|
| Experimental: 2A<br>Subjects received four doses of PCV13i at 3 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular<br>* Other names: PCV13i;|
| Experimental: 3A<br>Subject received three doses of PCV13i at 7 to 11 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular<br>* Other names: PCV13i;|
| Active Comparator: 3B<br>Subject received three doses of PCV13 at 7 to 11 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* 0.5mL,Intramuscular<br>* Other names: Prevnar;|
| Experimental: 4A<br>Subjects received two doses of PCV13i at 12 to 23 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular<br>* Other names: PCV13i;|
| Active Comparator: 4B<br>Subjects received two doses of PCV13 at 12 to 23 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* 0.5mL,Intramuscular<br>* Other names: Prevnar;|
| Active Comparator: 5A<br>Subjects received one dose of PCV13i at 2 to 5 years old. | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular<br>* Other names: PCV13i;|
| Active Comparator: 5B<br>Subjects received one dose of PCV13 at 2 to 5 years old. | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* 0.5mL,Intramuscular<br>* Other names: Prevnar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of PCV13i in preventing pneumococcal infections | Occurance of adverse reactions in all subjects | Within 7 days post each vaccination | 
| Safety of PCV13i in preventing pneumococcal infections | Occurance of adverse reactions in all subjects | Within 30 days post each vaccination | 
| Immunogenicity of PCV13i in subjects of 2 months (at least 6 weeks) old (Arm 1A-1B) | Serotype-specific seropositivity rates of Immunoglobulin G GMC concentrations above 0.35ug/ml | 30 days post three doses | 
| Immunogenicity of PCV13i in subjects of 7 to 11 months old (Arm 4A-4B) | Serotype-specific seropositivity rates of Immunoglobulin G GMC concentrations above 0.35ug/ml | 30 days post three doses | 
| Immunogenicity of PCV13i in subjects of 12 months to 5 years old (Arm 5A, 5B, 6A, 6B) | Serotype-specific seropositivity rates of Immunoglobulin G GMC concentrations above 0.35ug/ml | 30 days post last dose of vaccination | 
| Immunogenicity of PCV13i in subjects of age 50 years old and above (Arm 6A, 6B, 7A, 7B) | Serotype-specific seropositivity rates of Immunoglobulin G GMC concentrations above 0.35ug/ml | 30 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immuogenicity in terms of GMT in subjects of 2 months (at least 6 weeks) old (Arm 1A-1B) | GMT of serotype-specific OPA antibody with the titer of ≥1:8 ratio | 30 days post three doses | 
| Immunogenicity in terms of IgG concentration in subjects of 2 months (at least 6 weeks) old (Arm 1A-1B) | Serotype-specific Immunoglobulin G with a concentration of ≥1.0μg/ml | 30 days post three doses | 
| Safety of PCV13i in terms of in subjects of 2 months (at least 6 weeks) old (Arm 1A-1B) | Occurance of SAE in subjects of this age group | 6 months post one to three doses of vaccination | 
| Immuogenicity in terms of GMT in subjects of 7 to 11 months old (Arm 3A-3B) | GMT of serotype-specific OPA antibody with the titer of ≥1:8 ratio | 30 days post two doses | 
| Immuogenicity in terms of GMT in subjects of 12 months to 5 years old (Arm 4A, 4B, 5A, 5B) | GMT of serotype-specific OPA antibody with the titer of ≥1:8 ratio | 30 days post last dose of vaccination | 
| Immunogenicity in terms of IgG concentration in subjects of 7 to 11 months old (Arm 3A-3B) | Serotype-specific Immunoglobulin G with a concentration of ≥1.0μg/ml | 30 days post two doses | 
| Immunogenicity in terms of IgG concentration in subjects of 12 months to 5 years old (Arm 4A, 4B, 5A, 5B) | Serotype-specific Immunoglobulin G with a concentration of ≥1.0μg/ml | 30 days post last dose of vaccination | 
| Safety of PCV13i in terms of SAE in subjects of 7 to 11 months old (Arm 3A-3B) | Occurance of SAE in subjects of this age group | 6 months post two doses | 
| Safety of PCV13i in terms of SAE in subjects of 12 months to 5 years old (Arm 4A, 4B, 5A, 5B) | Occurance of SAE in subjects of this age group | 6 months post last dose of vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCV13, 13 valent Pneumococcal conjugate vaccine, Pneumococcal Infections, Safety, Immunogenicity