Study Evaluating 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants

• ClinicalTrials.gov Identifier: NCT00475033
• Recruitment Status: Completed
• First Posted: May 17, 2007
• Results First Posted: June 4, 2010
• Last Update Posted: April 21, 2011
• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by: Wyeth is now a wholly owned subsidiary of Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Vaccines, Pneumococcal Conjugate Vaccine	Biological: 13-valent Pneumococcal Conjugate Vaccine; Biological: 7-valent pneumococcal conjugate vaccine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 603 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: June 2007
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: May 2009

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 1 month after 2 doses of NeisVac-C® in the infant series (7 months of age) ]
   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%.
2. 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 [ Time Frame: 1 month after 2 doses of NeisVac-C® in the infant series (7 months of age) ]
   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.
3. Percentage of Subjects Achieving Predefined Antibody Level to Pertussis Antigens in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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%.
4. Geometric Mean Concentration (GMC) of Pertussis Antigens in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series [ Time Frame: 1 month after the 3-dose Infant Series (7 months of age) ]
   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.
5. 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 [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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%.
6. Geometric Mean Concentration (GMC) of PRP in Hib in the 13vPnC Group Relative to 7vPnC Group After the 3-dose Infant Series [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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.

Secondary Outcome Measures :

1. 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® [ Time Frame: 1 month after the toddler dose of NeisVac-C® (13 months of age) ]
   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%.
2. Geometric Mean Titer (GMT) of Meningococcal C Antigen in the 13vPnC Group Relative to 7vPnC Group After the Toddler Dose [ Time Frame: 1 month after the toddler dose (13 months of age) ]
   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.
3. 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 [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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%.

Other Outcome Measures:

1. Percentage of Subjects Achieving Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 μg/mL in the 13vPnC Group After the 3-dose Infant Series [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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.
2. Geometric Mean Concentration (GMC) for Pneumococcal IgG Antibody in 13vPnC Group After the 3-dose Infant Series [ Time Frame: 1 month after the 3-dose infant series (7 months of age) ]
   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.
3. Percentage of Subjects Achieving Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 μg/mL in the 13vPnC Group After the Toddler Dose [ Time Frame: 1 month after the toddler dose (13 months of age) ]
   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.
4. Geometric Mean Concentration (GMC) for Pneumococcal IgG Antibody in 13vPnC Group After the Toddler Dose [ Time Frame: 1 month after the toddler dose (13 months of age) ]
   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.
5. Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 1 (2 Months of Age) [ Time Frame: Within 4 days after dose (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.
6. Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 2 (4 Months of Age) [ Time Frame: Within 4 days after dose (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.
7. Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Infant Series Dose 3 (6 Months of Age) [ Time Frame: Within 4 days after dose (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.
8. Percentage of Subjects Reporting Pre-specified Local Reactions in the 13vPnC and 7vPnC Groups: Toddler Dose (12 Months of Age) [ Time Frame: Within 4 days after 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.
9. Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 1 (2 Months of Age) [ Time Frame: Within 4 days after dose (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.
10. Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 2 (4 Months of Age) [ Time Frame: Within 4 days after dose (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.
11. Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Infant Series Dose 3 (6 Months of Age) [ Time Frame: Within 4 days after dose (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.
12. Percentage of Subjects Reporting Pre-specified Systemic Events in the 13vPnC and 7vPnC Group: Toddler Dose (12 Months of Age) [ Time Frame: Within 4 days after 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.

Eligibility Criteria

• Ages Eligible for Study: 42 Days to 98 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Calgary, Alberta, Canada, T3B 6A8

Edmonton, Alberta, Canada, T5N 4A3

Canada, British Columbia

Coquitlam, British Columbia, Canada, V3C 4J2

Surrey, British Columbia, Canada, V3R 8P8

Vancouver, British Columbia, Canada, V6H 3N1

Canada, Manitoba

Winnipeg, Manitoba, Canada, R3A 1M3

Winnipeg, Manitoba, Canada, R3E 0W3

Canada, Nova Scotia

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Quebec

Montreal, Quebec, Canada, H3H 1P3

Montreal, Quebec, Canada, H3T 1C5

Quebec City, Quebec, Canada, G1E 7G9

Sponsors and Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor; Wyeth is now a wholly owned subsidiary of Pfizer
• Principal Investigator: Trial Manager; For Canada, clintrialparticipation@wyeth.com

More Information

• Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
• ClinicalTrials.gov Identifier: NCT00475033
• Other Study ID Numbers: 6096A1-3008
• First Posted: May 17, 2007
• Results First Posted: June 4, 2010
• Last Update Posted: April 21, 2011
• Last Verified: April 2011

Additional relevant MeSH terms:

Vaccines; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs