Phase I Clinical Trial of a Candidate PCV13 in Healthy People Aged 6 Weeks and Above

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 I Clinical Trial to Preliminary 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: vaccine 1A<br>Subjects received one dose of PCV13i at 18 to 49 years old | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Experimental: vaccine 2A<br>Subjects received one dose of PCV13i at 50 years old and above | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Experimental: vaccine 3A<br>Subjects received one dose of PCV13i at 6 to 17 years old | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Experimental: vaccine 4A<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 other name:PCV13i<br>|
| Experimental: vaccine 5A<br>Subjects received two doses of PCV13i at 7 months to 2 years old | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Experimental: vaccine 6A<br>Subjects received three doses of PCV13i at 3,4,5 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Experimental: vaccine 7A<br>Subjects received three doses of PCV13i at 2,4,6 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine（CRM197,TT）<br>* 0.5mL,Intramuscular other name:PCV13i<br>|
| Active Comparator: vaccine 7B<br>Subjects received three doses of PCV13 at 2,4,6 months of age | Biological: 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine<br>* 0.5mL,Intramuscular other name:Prevnar<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety items of adverse reactions | Occurrence of adverse reactions of each subject(Arm 1A-7B) | within 7 days post each vaccination | 
| Safety items of SAE | Occurrence of SAE of each subject(Arm 1A-7B) | within 6 months post last vaccination | 
| Safety items of Hematological examination | Occurrence of abnormal changes of Hematological examination in subjects of 2 years old and above(Arm 1A-4A) | day 4 post vaccination | 
| Safety items of Urine test | Occurrence of abnormal changes of Urine test in subjects of 2 years old and above(Arm 1A-4A) | day 4 post vaccination | 
| Safety items of Blood chemistry test | Occurrence of abnormal changes of Blood chemistry test in subjects of 2 years old and above(Arm 1A-4A) | day 4 post vaccination | 
| Safety items of pressure value | Occurrence of abnormal changes of pressure valus in subjects of 18 years old and above(Arm 1A-2A) | day 4 post vaccination | 
| Safety items of heart rate | Occurrence of abnormal changes of heart rate in subjects of 18 years old and above(Arm 1A-2A) | day 4 post vaccination | 
| Safety items of adverse reactions | Occurrence of adverse reactions of each subject(Arm 1A-7B) | within 30 days post each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunogencity items of seropositivity rates by ELISA | Serotype-specific seropositivity rates of Immunoglobulin G concentrations above 0.35ug/ml in subjects aged 2 and 3 months post last vaccination(Arm 6A-7B) | day 30 post last vaccination | 
| immunogencity items of GMC by ELISA | Serotype specific IgG GMC of each the pneumococcal serotypes in subjects aged 2 and 3 months post last vaccination(Arm 6A-7B) | day 30 post last vaccination | 
| immunogencity items of GMI by ELISA | Serotype-specific GMI value pneumococcfor each of the pneunococcal serotypes in subjects aged 2 and 3 months post last vaccination(Arm 6A-7B) | day 30 post last vaccination | 
| immunogencity items of GMT | Serological response in terms of GMT for each of the pneumococcal serotypes tested by OPA in subjects aged 2 months post last vaccination(7A、7B) | day 30 post last 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