A Safety And Immunogenicity Study Of A 13-valent Pneumococcal Conjugate Vaccine In Japanese Subjects Aged 6 To 64 Years.

A PHASE 3, MULTICENTER, SINGLE-ARM, OPEN-LABEL STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SINGLE DOSE OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN JAPANESE SUBJECTS AGED 6 TO 64 YEARS WHO ARE CONSIDERED TO BE AT INCREASED RISK OF PNEUMOCOCCAL DISEASE AND WHO ARE NAIVE TO PNEUMOCOCCAL VACCINES

This study is to evaluate the safety, tolerability and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese subjects aged 6 to 64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: 13-valent pneumococcal conjugate vaccine

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 813-0017
    • Fukuoka Children's Hospital
  • Fukuoka, Japan, 812-0025
    • Medical Co.LTA PS Clinic
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Aichi
    • Nagoya, Aichi, Japan, 457-8511
      • Daido Clinic
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 721-8511
      • Fukuyama City Hospital
    • Fukuyama, Hiroshima, Japan, 721-0927
      • Nippon Kokan Fukuyama Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0013
      • Kawasaki Municipal Hospital
  • Nagano
    • Suzaka, Nagano, Japan, 382-8577
      • Nagano Prefectural Shinshu Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese males and females aged 6 to <65 years at enrollment.
• Subjects with an increased risk of pneumococcal disease determined by documented medical history, physical examination, and clinical judgment of the investigator.

Exclusion Criteria:

• Previous vaccination with any licensed or investigational pneumococcal vaccine, or planned receipt during study participation.
• End-stage disease including but not limited to metastatic malignancy, severe chronic obstructive pulmonary disease (COPD) requiring supplemental oxygen, or end-stage renal disease with or without dialysis.
• Graft-versus-host disease (GVHD), history of solid organ transplant within 6 months before investigational product administration or history of HSCT, or potential for solid organ transplant or HSCT during study participation.
• Receipt of cytotoxic chemotherapy or blood products within 3 months before investigational product administration or anti-B-cell antibodies within 6 months before investigational product administration through completion of study participation.
• Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.
• Documented S pneumoniae infection within the past 5 years before investigational product administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 13-valent pneumococcal conjugate vaccine	Biological: 13-valent pneumococcal conjugate vaccine; A single dose (0.5 mL) will be administered intramuscularly into the deltoid muscle at visit 1.; Other Names: 13vPnC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Pre-Specified Local Reactions Within 7 Days After Vaccination in Participants Aged Between 6 to <18 Years	Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (0.5 to 2.0 centimeter [cm]), moderate (greater than [>] 2.0 to 7.0 cm) and severe (>7.0 cm) for participants aged 6 to <12 years, and as mild (2.5 to 5.0 cm), moderate (>5.0 to 10.0 cm) and, severe (>10.0 cm) for participants aged 12 to <18 years. Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).	Day 1 up to Day 7
Percentage of Participants Reporting Pre-Specified Local Reactions Within 14 Days After Vaccination in Participants Aged Between 18 to <65 Years	Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (2.5 to 5.0 cm), moderate (>5.0 to 10.0 cm) and, severe (>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).	Day 1 up to Day 14
Percentage of Participants Reporting Systemic Events and Use of Antipyretic or Pain Medication Within 7 Days After Vaccination in Participants Aged Between 6 to <18 Years	Systemic events included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain, and were recorded by using an e-diary. Use of antipyretic or pain medication was also collected by using an e-diary. Fever was graded as 37.5 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (greater than or equals to [>=] 6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity).	Day 1 up to Day 7
Percentage of Participants Reporting Systemic Events and Use of Antipyretic or Pain Medication Within 14 Days After Vaccination in Participants Aged Between 18 to <65 Years	Systemic events included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain, and were recorded by using an e-diary. Use of antipyretic or pain medication was also collected by using an e-diary. Fever was graded as 37.5 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity).	Day 1 up to Day 14
Percentage of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect.	signing of informed consent form (Day 1) up to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at Pre-vaccination and 1 Month After Vaccination	Antibody-mediated serum OPA against each of the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) was measured centrally using a quantitative functional microcolony OPA (mcOPA) assay. Results were expressed as OPA titers. OPA titers were logarithmically transformed for analysis; geometric means calculated and expressed as geometric mean titers (GMTs). Two (2)-sided 95% CIs were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed based on the Student t distribution. OPA titer was expressed as reciprocal of highest serum dilution.	Pre-vaccination and 1 month after vaccination
Geometric Mean Fold Rises (GMFRs) in Serotype-specific OPA Titers 1 Month After Vaccination	OPA GMFRs were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. GMFRs were computed as the fold rise in titer value at 1 month after vaccination compared to baseline (pre-vaccination). The CIs for GMFRs were back transformations of a CI based on the Student t distribution for the mean difference of the log-transformed assay results before vaccination and 1 month after vaccination.	Pre-vaccination to 1 month after vaccination
Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at Pre-vaccination and 1 Month After Vaccination	Pneumococcal IgG antibody against each of the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) was measured centrally using direct binding Luminex assay. Results were expressed as IgG concentrations. IgG concentrations were logarithmically transformed for analysis; geometric means calculated and expressed as GMCs. Two (2)-sided 95% CIs were constructed by back transformation of the CI for the mean of the logarithmically transformed assay results computed based on the Student t distribution.	Pre-vaccination and 1 month after vaccination
GMFRs in Serotype-specific IgG From Before Vaccination to 1 Month After Vaccination	IgG GMFRs were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. GMFRs were computed as the fold rise in concentrations at 1 month after vaccination compared to baseline (pre-vaccination). The CIs for GMFRs were back transformations of a CI based on the Student t distribution for the mean difference of the log-transformed assay results before vaccination and 1 month after vaccination.	Pre- vaccination to 1 month after vaccination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Yamazaki Y, Ikeda M, Imada T, Furuno K, Mizukami T, de Solom R, Shoji Y, Oe M, Aizawa M, Giardina PC, Schmoele-Thoma B, Scott DA. A phase 3, multicenter, single-arm, open-label study to assess the safety, tolerability, and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese participants aged 6-64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines. Vaccine. 2021 Oct 15;39(43):6414-6421. doi: 10.1016/j.vaccine.2021.08.106. Epub 2021 Sep 23.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2018
• Primary Completion (Actual): November 16, 2018
• Study Completion (Actual): November 16, 2018

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: B1851172; 2018-003054-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes