Study Evaluating 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants

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

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.

Study Overview

• Status: Completed
• Conditions: Vaccines, Pneumococcal Conjugate Vaccine
• Intervention / Treatment: Biological: 13-valent Pneumococcal Conjugate Vaccine; Biological: 7-valent pneumococcal conjugate vaccine

• Study Type: Interventional
• Enrollment (Actual): 603
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
    • Edmonton, Alberta, Canada, T5N 4A3
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3C 4J2
    • Surrey, British Columbia, Canada, V3R 8P8
    • Vancouver, British Columbia, Canada, V6H 3N1
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
    • Winnipeg, Manitoba, Canada, R3E 0W3
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
    • Montreal, Quebec, Canada, H3T 1C5
    • Quebec City, Quebec, Canada, G1E 7G9

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 μg/mL in the 13vPnC Group After the 3-dose Infant Series	Percentage of subjects achieving World Health Organization (WHO) predefined antibody threshold ≥0.35μg/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.	1 month after the 3-dose infant series (7 months of age)
Geometric Mean Concentration (GMC) for Pneumococcal IgG Antibody in 13vPnC Group After the 3-dose Infant Series	Antibody geometric mean concentration (GMC) as measured by μg/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% CI were evaluated. 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.	1 month after the 3-dose infant series (7 months of age)
Percentage of Subjects Achieving Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 μg/mL in the 13vPnC Group After the Toddler Dose	Percentage of subjects achieving WHO predefined antibody threshold ≥0.35μg/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.	1 month after the toddler dose (13 months of age)
Geometric Mean Concentration (GMC) for Pneumococcal IgG Antibody in 13vPnC Group After the Toddler Dose	Antibody geometric mean concentration (GMC) as measured by μg/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% CI were evaluated. 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.	1 month after the toddler dose (13 months of age)
Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 1 (2 Months of Age)	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category.	Within 4 days after dose (2 months of age)
Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 2 (4 Months of Age)	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category.	Within 4 days after dose (4 months of age)
Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 3 (6 Months of Age)	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category.	Within 4 days after dose (6 months of age)
Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Toddler Dose (12 Months of Age)	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category.	Within 4 days after dose (12 months of age)
Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 1 (2 Months of Age)	Systemic events (any fever ≥38 degrees Celsius [C], decreased appetite, irritability, increased sleep, and decreased sleep were reported using an electronic diary. Subjects may be represented in more than 1 category.	Within 4 days after dose (2 months of age)
Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 2 (4 Months of Age)	Systemic events (any fever ≥38 degrees Celsius [C], decreased appetite, irritability, increased sleep, and decreased sleep were reported using an electronic diary. Subjects may be represented in more than 1 category.	Within 4 days after dose (4 months of age)
Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 3 (6 Months of Age)	Systemic events (any fever ≥38 degrees Celsius [C], decreased appetite, irritability, increased sleep, and decreased sleep were reported using an electronic diary. Subjects may be represented in more than 1 category.	Within 4 days after dose (6 months of age)
Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Toddler Dose (12 Months of Age)	Systemic events (any fever ≥38 degrees Celsius [C], decreased appetite, irritability, increased sleep, and decreased sleep were reported using an electronic diary. Subjects may be represented in more than 1 category.	Within 4 days after dose (12 months of age)

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Trial Manager, For Canada, clintrialparticipation@wyeth.com

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: May 15, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): April 21, 2011
• Last Update Submitted That Met QC Criteria: April 18, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 6096A1-3008