Trial Evaluating a 13-valent Pneumococcal Conjugate Vaccine Given With Diphtheria, Tetanus, and Acellular Pertussis Vaccine (DTaP) in Healthy Japanese Infants

Study Overview
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Brief Summary
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Subjects will be randomly assigned to 1 of 3 groups to receive the following vaccines: Group 1: 13-valent pneumococcal conjugate vaccine (13vPnC) and diphtheria, tetanus, and acellular pertussis vaccine (DTaP), Group 2: 7-valent pneumococcal conjugate vaccine (7vPnC) and DTaP, Group 3: DTaP alone. Group 3 subjects will also receive catch-up doses of Prevenar (commercial product of Prevenar in Japan) 13vPnC and 7vPnC will be blinded, and DTaP will be open-label. The main purpose of the study is to determine if the immune responses to 13vPnC are comparable to the immune responses to 7vPnC and if the immune responses to 13vPnC given with DTaP are comparable to those induced by DTaP given alone. In addition, the study aims to evaluate the side effects (safety profile) after vaccination of 13vPnC and 7vPnC when given with DTaP in healthy Japanese infants.

Official Title
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A Phase 3, Randomized, Active-controlled, Double-blind Trial Evaluating The Safety, Tolerability, And Immunogenicity Of A 13-valent Pneumococcal Conjugate Vaccine Given With Dtap Compared To Open-label Dtap In Healthy Japanese Infants

Conditions
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Healthy Subjects

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)
* Biological: diphtheria, tetanus, and acellular pertussis vaccine (DTaP)
* Biological: 7-valent pneumococcal conjugate vaccine (7vPnC)
* Biological: DTaP
* Biological: DTaP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 3 to 6 months of age at the enrollment. Available for the entire study period and whose parent/legal guardian can be reached by telephone. Healthy infant as determined by medical history, physical examination, and judgement of the investigator. Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal, diphtheria, tetanus, or pertussis vaccines. A previous anaphylactic reaction to any vaccine or vaccine-related component. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate any type of injection. History of culture-proven invasive disease caused by S pneumoniae (eg, meningitis, bacteremia, osteomyelitis, arthritis). Infant who is a direct descendant (child, grandchild) of the study site personnel.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 6 Months

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Experimental | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL per dose, 4 doses<br>Biological: diphtheria, tetanus, and acellular pertussis vaccine (DTaP)<br>* 0.5 mL per dose, 4 doses<br>|
| Active Comparator: 2<br>Active comparator | Biological: 7-valent pneumococcal conjugate vaccine (7vPnC)<br>* 0.5 mL per dose, 4 doses<br>Biological: DTaP<br>* 0.5 mL per dose, 4 doses<br>|
| Active Comparator: 3<br>Active comparator | Biological: DTaP<br>* 0.5 mL per dose, 4 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series | Percentage of participants achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest response observed among the 7 common serotypes in the group was taken as reference. | 1 month after the infant series | 
| Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 7 Common Serotypes 1 Month After the Infant Series | Antibody geometric mean concentration (GMC) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. | 1 month after the infant series | 
| Percentage of Participants Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Infant Series | Predefined antibody levels were 0.1 International Units/mL (IU/mL) for diphtheria, 0.01 IU/mL for tetanus, 5 Enzyme-linked Immunosorbent Assay (ELISA) units/mL (EU/mL) for pertussis toxoid (PT), and 5 EU/mL for filamentous hemagglutinin (FHA). | 1 month after the infant series | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 6 Additional Serotypes 1 Month After the Infant Series | Antibody GMC for 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. GMs were calculated using all participants with available data for the specified blood draw. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest GMC observed among the 7 common serotypes in the group was taken as reference. | 1 month after the infant series | 
| Percentage of Participants Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level >=0.35 mcg/mL 1 Month After the Toddler Dose | Percentage of participants achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest response observed among the 7 common serotypes in the group was taken as reference. | 1 month after the toddler dose | 
| Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose | Antibody GMC as measured by mcg/mL for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest GMC observed among the 7 common serotypes in the group was taken as reference. | 1 month after the toddler dose | 
| Percentage of Participants Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Toddler Dose | Predefined antibody level was 0.1 IU/mL for diphtheria, 0.01 IU/mL for tetanus, 5 EU/mL for PT, and 5 EU/mL for FHA. | 1 month after the toddler dose | 
| Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibodies 1 Month After the Infant Series | GMC was measured in IU/mL and corresponding 2-sided 95% CI were evaluated for diphtheria and tetanus antibodies. | 1 month after the infant series | 
| Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibodies 1 Month After the Infant Series | GMC was measured in EU/mL and corresponding 2-sided 95% CI were evaluated for PT and FHA antibodies. | 1 month after the infant series | 
| Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibody 1 Month After the Toddler Dose | GMC was measured in IU/mL and corresponding 2-sided 95% CI were evaluated for diphtheria and tetanus antibodies. | 1 month after the toddler dose | 
| Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibody 1 Month After the Toddler Dose | GMC was measured in EU/mL and corresponding 2-sided 95% CI were evaluated for PT and FHA antibodies. | 1 month after the toddler dose | 

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