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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Biological: 13-valent pneumococcal conjugate vaccine (13vPnC); Biological: diphtheria, tetanus, and acellular pertussis vaccine (DTaP); Biological: 7-valent pneumococcal conjugate vaccine (7vPnC); Biological: DTaP

• Study Type: Interventional
• Enrollment (Actual): 551
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1394
    • National Hospital Organization Fukuoka National Hospital
  • Fukuoka, Japan, 816-0094
    • Harada Clinic
  • Kumamoto, Japan, 860-0812
    • Hattori Pediatric Clinic
  • Kumamoto, Japan, 860-0834
    • Medical Corporation Seiaikai Seguchi Pediatric Clinic
  • Kumamoto, Japan, 862-0924
    • Medical Corporation Oukakai Sakuranbo Kodomo Clinic
  • Okayama, Japan, 701-0205
    • Momotaro Clinic
  • Chiba
    • Funabashi, Chiba, Japan, 273-0035
      • Sunrise Children's Clinic
    • Isumi-city, Chiba, Japan, 299-4503
      • Sotobo Children's Clinic
  • Ehime
    • Matsuyama-city, Ehime, Japan, 790-8524
      • Matsuyama Red Cross Hospital
  • Fukuoka
    • Higashi-ku, Fukuoka-city, Fukuoka, Japan, 813-0036
      • Fukazawa Pediatric Clinic
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 720-8520
      • National Hospital Organization FUKUYAMA MEDICAL CENTER
    • Kure, Hiroshima, Japan, 737-0023
      • National Hospital Organization Kure Medical Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0023
      • Nakata pediatric clinic
    • Sapporo, Hokkaido, Japan, 006-0831
      • Watanabe Pediatric Allergy Clinic
    • Sapporo, Hokkaido, Japan, 063-0831
      • Furuta Children's Clinic
    • Sapporo, Hokkaido, Japan, 065-0024
      • Motomachi pediatric clinic
    • Sapporo, Hokkaido, Japan, 065-8611
      • Tenshi Hospital
  • Kumamoto
    • Kikuchi-gun, Kumamoto, Japan, 869-1102
      • Yoshimoto Pediatrist Clinic
  • MIE
    • Suzuka, MIE, Japan, 510-0235
      • Shiroko Clinic
    • Tsu, MIE, Japan, 514-0125
      • National Mie Hospital
    • Tsu, MIE, Japan, 514-1101
      • National hospital Organization Mie Chuou Medical Center
  • Saitama
    • Kumagaya, Saitama, Japan, 360-0018
      • Children's Enomoto Clinic
    • Kumagaya-city, Saitama, Japan, 360-0812
      • Shibuya Clinic
  • Tokyo
    • Fuchu, Tokyo, Japan, 183-0042
      • Sakiyama Children's Clinic
    • Ota-ku, Tokyo, Japan, 146-0095
      • Okawa Children and Family Clinic
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development
    • Setagaya-ku, Tokyo, Japan, 157-0066
      • Seijo Sasamoto Pediatric And Allergy Clinic
    • Tachikawa-shi, Tokyo, Japan, 190-0002
      • Miyata Pediatric Clinic
    • Tama, Tokyo, Japan, 206-0011
      • Maehara Pediatric Clinic
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-0853
      • Childrens Clinic of Kose
    • Koushu-shi, Yamanashi, Japan, 404-0046
      • Medical Corporation Bunpoukai Amemiya Clinic
    • Tsuru-shi, Yamanashi, Japan, 402-0025
      • Medical corporation Seijinkai Takei Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Pre-Specified Local Reactions: Infant Series Dose 1 (3 to 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). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.	Within 7 days after Dose 1 of the infant series
Percentage of Participants Reporting Pre-Specified Local Reactions: Infant Series Dose 2 (4 to 8 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). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.	Within 7 days after Dose 2 of the infant series
Percentage of Participants Reporting Pre-Specified Local Reactions: Infant Series Dose 3 (5 to 10 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). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.	Within 7 days after Dose 3 of the infant series
Percentage of Participants Reporting Pre-Specified Local Reactions: Toddler Dose (12 to 15 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). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.	Within 7 days after the toddler dose
Percentage of Participants Reporting Pre-Specified Systemic Events: Infant Series Dose 1 (3 to 6 Months of Age)	Systemic events (any fever >= 37.5 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category.	Within 7 days after Dose 1 of infant series
Percentage of Participants Reporting Pre-Specified Systemic Events: Infant Series Dose 2 (4 to 8 Months of Age)	Systemic events (any fever >= 37.5 degrees C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category.	Within 7 days after Dose 2 of infant series
Percentage of Participants Reporting Pre-Specified Systemic Events: Infant Series Dose 3 (5 to 10 Months of Age)	Systemic events (any fever >= 37.5 degrees C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category.	Within 7 days after Dose 3 of infant series
Percentage of Participants Reporting Pre-Specified Systemic Events: Toddler Dose (12 to 15 Months of Age)	Systemic events (any fever >= 37.5 degrees C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category.	Within 7 days after the toddler dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Togashi T, Okada K, Yamaji M, Thompson A, Gurtman A, Cutler M, Aizawa M, Gruber WC, Scott DA. Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine Given With DTaP Vaccine in Healthy Infants in Japan. Pediatr Infect Dis J. 2015 Oct;34(10):1096-104. doi: 10.1097/INF.0000000000000819.

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2010
• Primary Completion (Actual): November 30, 2011
• Study Completion (Actual): November 30, 2011

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: September 10, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: vaccine; pneumococcal conjugate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: B1851056; 6096A1-3024 (Other Identifier: Alias Study Number)