Study Evaluating 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants

Study Overview
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Brief Summary
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The purpose of this study will be to evaluate the safety, tolerability and immunogenicity of 13-valent pneumococcal conjugate vaccine in healthy infants given with routine pediatric vaccinations in Canada. Immune responses induced by the infant series (NeisVac-C® and Pentacel®)and toddler dose(NeisVac-C®)of routine pediatric vaccines when administered with 13-valent pneumococcal conjugate vaccine will be studied for noninferiority to the immune responses when administered with 7-valent pneumococcal conjugate vaccine. Safety profile and immunogenicity of 13-valent pneumococcal conjugate vaccine will also be evaluated.

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 in Healthy Infants Given With Routine Pediatric Vaccinations in Canada

Conditions
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Vaccines, Pneumococcal Conjugate Vaccine

Intervention / Treatment
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* Biological: 13-valent Pneumococcal Conjugate Vaccine
* Biological: 7-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 2-month old infants (42 to 98 days) Available for the duration of the study and reachable by telephone Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal, Hib conjugate, diphtheria, tetanus, pertussis, polio, or meningococcal vaccine Previous anaphylactic reaction to any vaccine or vaccine-related component. Bleeding disorder, immune deficiency or suppression, or significant chronic or congenital disease Receipt of blood products or gamma globulin

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 98 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: 13-valent Pneumococcal Conjugate Vaccine<br>* 13-valent pneumococcal conjugate vaccine administered at 2-, 4-, 6-, and 12 months of age.<br>|
| Active Comparator: 2<br> | Biological: 7-valent pneumococcal conjugate vaccine<br>* 7-valent pneumococcal conjugate vaccine administered at 2-, 4-, 6-, and 12 months of age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Predefined Antibody Level ≥1:8 for Meningococcal C Serum Bactericidal Assay (SBA) in the 13vPnC Group Relative to 7vPnC Group After 2 Doses of NeisVac-C® in the Infant Series | Percentage of subjects achieving predefined antibody threshold ≥1:8 along with the corresponding 95 percent (%) confidence interval (CI) for concomitant antigen meningococcal C SBA are presented. Non-inferiority was declared if the lower limit of the 2-sided 95% CI for the difference between the 2 treatment groups > -10%. | 1 month after 2 doses of NeisVac-C® in the infant series (7 months of age) | 
| Geometric Mean Titer (GMT) of Meningococcal C Antigen in the 13vPnC Group Relative to 7vPnC Group After 2 Doses of NeisVac-C® in the Infant Series | Antibody geometric mean titer of meningococcal C antigen are presented. GMT and corresponding 2-sided 95% CI were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed using the Student t distribution. In addition, the 2-sided 95% confidence interval on the ratio of the geometric means for 13vPnC relative to 7vPnC was constructed by back transformation of the Student t distribution for the mean difference of the measures on the logarithmic scale. | 1 month after 2 doses of NeisVac-C® in the infant series (7 months of age) | 
| Percentage of Subjects Achieving Predefined Antibody Level to Pertussis Antigens in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series | Percentage of subjects achieving predefined antibody threshold ≥5 enzyme-linked immunosorbent assay (ELISA) units per mL (EU/mL) along with the corresponding 95 % CI for concomitant antigens pertussis (pertussis toxoid [PT], filamentous hemagglutinin [FHA], and pertactin [PRN]) and ≥ 2.2 EU/mL fimbrial agglutinogens (FIM) are presented. Non-inferiority was declared if the lower limit of the 2-sided 95% CI for the difference between the 2 treatment groups > -10%. | 1 month after the 3-dose infant series (7 months of age) | 
| Geometric Mean Concentration (GMC) of Pertussis Antigens in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series | Antibody geometric mean concentration of pertussis antigens (PT, FHA, PRN, and FIM) as measured by EU/mL are presented. GMC and corresponding 2-sided 95% CI were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed using the Student t distribution. In addition, the 2-sided 95% confidence intervals on the ratio of the GMCs for 13vPnC relative to 7vPnC were constructed by back transformation of the Student t distribution for the mean difference of the measures on the logarithmic scale. | 1 month after the 3-dose Infant Series (7 months of age) | 
| Percentage of Subjects Achieving Predefined Antibody Level ≥0.15 Micrograms Per mL (μg/mL) for Polyribosylribitol Phosphate (PRP) in Hib in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series | Percentage of subjects achieving predefined antibody threshold ≥0.15 μg/mL along with the corresponding 95 percent (%) confidence interval (CI) for concomitant antigen PRP in Hib are presented. Non-inferiority was declared if the lower limit of the 2-sided 95% CI for the difference between the 2 treatment groups > -10%. | 1 month after the 3-dose infant series (7 months of age) | 
| Geometric Mean Concentration (GMC) of PRP in Hib in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series | Antibody geometric mean concentration of PRP in Hib as measured by µg/mL are presented. GMC and corresponding 2-sided 95% CI were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed using the Student t distribution. In addition, the 2-sided 95% confidence interval on the ratio of the GMCs for 13vPnC relative to 7vPnC was constructed by back transformation of the Student t distribution for the mean difference of the measures on the logarithmic scale. | 1 month after the 3-dose infant series (7 months of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Predefined Antibody Level ≥1:8 for Meningococcal C SBA in the 13vPnC Group Relative to 7vPnC Group After the Toddler Dose of NeisVac-C® | Percentage of subjects achieving predefined antibody threshold ≥1:8 along with the corresponding 95% CI for concomitant antigen meningococcal C SBA are presented. Non-inferiority was declared if the lower limit of the 2-sided 95% CI for the difference between the 2 treatment groups > -10%. | 1 month after the toddler dose of NeisVac-C® (13 months of age) | 
| Geometric Mean Titer (GMT) of Meningococcal C Antigen in the 13vPnC Group Relative to 7vPnC Group After the Toddler Dose | Antibody geometric mean titer of meningococcal C antigen are presented. GMT and corresponding 2-sided 95% CI were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed using the Student t distribution. In addition, the 2-sided 95% confidence interval on the ratio of the GMs for 13vPnC relative to 7vPnC was constructed by back transformation of the Student t distribution for the mean difference of the measures on the logarithmic scale. | 1 month after the toddler dose (13 months of age) | 
| Percentage of Subjects Achieving Predefined Antibody Level ≥1.0 μg/mL for PRP in Hib in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series | Percentage of subjects achieving predefined antibody threshold ≥1.0 μg/mL along with the corresponding 95% CI for concomitant antigen PRP in Hib are presented. Non-inferiority was declared if the lower limit of the 2-sided 95% CI for the difference between the 2 treatment groups > -10%. | 1 month after the 3-dose infant series (7 months of age) |