A Phase III Clinical Trial of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants

Study Overview
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Brief Summary
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In order to evaluate immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine produced by Beijing Minhai Biotechnology Co., Ltd., a randomized, double-blind, parallel-controlled phase III clinical trial is planned to conduct in healthy infants aged 2 months in China.

Detailed Description
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There will be two arms. 1200 healthy infants aged 2 months will be randomly assigned (1:1) to receive an experimental vaccine or a comparator vaccine in Month 0,2 and 4 (primary vaccination). All of them will receive a fourth dose as booster vaccination in Month 10.

Official Title
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A Randomized, Double-blind, Parallel-Controlled Phase III Clinical Trial of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants

Conditions
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Pneumonia

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine
* Biological: Prevnar 13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 42-77 days old on the day of inclusion Subjects' legal guardians are able to understand and sign the informed consent Subjects' legal guardians can and will comply with the requirements of the protocol Subjects with temperature <=37.0°C on axillary setting Exclusion Criteria for First Vaccination: Preterm infants or low birth weight infants Any administration history of pneumococcal polysaccharide vaccine or pneumococcal conjugate vaccine A medical history of culture-confirmed invasive disease caused by Streptococcus pneumonia Subject who has allergic history or serious adverse reaction history after vaccination such as allergies, hives, difficulty in breathing, angioedema or abdominal pain Subject with congenital malformation, developmental disorder, genetic defects or severe malnutrition Subject with epilepsy, a history of seizures or convulsions, or a family history of mental illness Known or suspected immune deficiency or immune suppression Diagnosed coagulation abnormalities (such as clotting factor deficiency, coagulation disorders, platelet disorder) or significant bruising or blood clotting disorder Had immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (not including allergic rhinitis corticosteroid spray treatment, acute uncomplicated dermatitis surfaces corticosteroid therapy) in the past 6 months Any prior administration of blood products in last 3 months Any prior administration of any attenuated live vaccine in last 14 days Any prior administration of subunit or inactivated vaccines in last 7 days Any acute infection or serious infection needing systemic antibiotics or antiviral treatment in last 7 days Any fever with temperature >=38.0°C on axillary setting in last 3 days Any other factors judged by investigator, that may interfere subject's compliance with the protocol Exclusion Criteria for Second/Third and Booster Vaccination: If one of the following (1) to (3) adverse events (AE) occurs, further vaccination is prohibited, but other study steps can be continued according to the judgment of the investigators; If one of the following (4) to (5) adverse events occurs, the investigator shall determine whether to continue the following vaccination. In the event of one of the following adverse events (6) to (7), vaccination may be postponed within the time window specified in the protocol. （1）The subjects have suffered from severe adverse events caused by the previous vaccination. （2）The subjects suffered from severe allergic reactions or hypersensitivity after the previous vaccination. （3）Known or suspected autoimmune diseases or immunodeficiency diseases，including HIV infection. （4）The occurrence of acute or emerging chronic diseases at the time of vaccination. （5）Other reactions (including severe pain, severe swelling, severe restriction of movement, persistent high fever, severe headache, or other systemic or local reactions) judged by the investigators. （6）Acute illness (acute illness refers to moderate or severe illness with or without fever) at the time of vaccination. （7）The axillary temperature >37.0℃ at the time of vaccination.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 77 Days

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: 13-valent pneumococcal conjugate vaccine<br>Single 0.5 ml dose will be given via intramuscular injection in Month 0,2,4 and 10 | Biological: 13-valent pneumococcal conjugate vaccine<br>* 0.5ml vaccine produced by Beijing Minhai Biotechnology Co., Ltd.,three doses with 2 month interval, a booster dose 10 months after the first dose<br>|
| Active Comparator: Prevnar 13<br>Single 0.5 ml dose will be given via intramuscular injection in Month 0,2,4 and 10 | Biological: Prevnar 13<br>* 0.5ml vaccine produced by Wyeth,three doses with 2 month interval, a booster dose 10 months after the first dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 0.35 ug/mL 30 days after primary vaccination | Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 0.35 ug/mL 30 days after primary vaccination | 30 days after primary vaccination | 
| Geometric mean concentration (GMC) of serotype-specific pneumococcal IgG antibody 30 days after primary vaccination | Geometric mean concentration (GMC) of serotype-specific pneumococcal IgG antibody 30 days after primary vaccination | 30 days after primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 1.0 ug/mL 30 days after primary vaccination | Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 1.0 ug/mL 30 days after primary vaccination | 30 days after primary vaccination | 
| Geometric mean fold increase (GMI) of serotype-specific pneumococcal IgG antibody 30 days after primary vaccination | Geometric mean fold increase (GMI) of serotype-specific pneumococcal IgG antibody 30 days after primary vaccination | 30 days after primary vaccination | 
| Proportion of subjects with serotype-specific geometric mean titer measured by OPA ≥1:8 30 days after primary vaccination | Proportion of subjects with serotype-specific geometric mean titer measured by OPA ≥1:8 30 days after primary vaccination | 30 days after primary vaccination | 
| Geometric mean titer (GMT) of serotype-specific pneumococcal IgG antibody measured by OPA 30 days after primary vaccination | Geometric mean titer (GMT) of serotype-specific pneumococcal IgG antibody measured by OPA 30 days after primary vaccination | 30 days after primary vaccination | 
| Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 0.35 ug/mL 30 days after booster vaccination | Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 0.35 ug/mL 30 days after booster vaccination | 30 days after booster vaccination | 
| Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 1.0 ug/mL 30 days after booster vaccination | Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 1.0 ug/mL 30 days after booster vaccination | 30 days after booster vaccination | 
| Geometric mean concentration (GMC) of serotype-specific pneumococcal IgG antibody 30 days after booster vaccination | Geometric mean concentration (GMC) of serotype-specific pneumococcal IgG antibody 30 days after booster vaccination | 30 days after booster vaccination | 
| Proportion of subjects with serotype-specific geometric mean titer measured by OPA ≥1:8 30 days after booster vaccination | Proportion of subjects with serotype-specific geometric mean titer measured by OPA ≥1:8 30 days after booster vaccination | 30 days after booster vaccination | 
| Geometric mean titer (GMT) of serotype-specific pneumococcal IgG antibody measured by OPA 30 days after booster vaccination | Geometric mean titer (GMT) of serotype-specific pneumococcal IgG antibody measured by OPA 30 days after booster vaccination | 30 days after booster vaccination | 
| Incidence of adverse reactions (including systemic and local adverse reaction) 30 days after each dose of vaccination | Incidence of adverse reactions (including systemic and local adverse reaction) 30 days after each dose of vaccination | 30 days after each dose of vaccination | 
| Incidence of severe adverse event (SAE) within 6 months after the first doseof vaccination | Incidence of severe adverse event (SAE) within 6 months after the first doseof vaccination | 6 months after the first doseof vaccination | 
| Incidence of severe adverse event (SAE) 30 days after booster vaccination | Incidence of severe adverse event (SAE) 30 days after booster vaccination | 30 days after booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal conjugate vaccine, immunogenicity, safety