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

• ClinicalTrials.gov Identifier: NCT03571607
• Recruitment Status: Completed
• First Posted: June 27, 2018
• Results First Posted: December 10, 2019
• Last Update Posted: February 18, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 20, 2018
• First Posted Date: June 27, 2018
• Results First Submitted Date: November 20, 2019
• Results First Posted Date: December 10, 2019
• Last Update Posted Date: February 18, 2020
• Actual Study Start Date: July 12, 2018
• Actual Primary Completion Date: November 16, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2019)

• Percentage of Participants Reporting Pre-Specified Local Reactions Within 7 Days After Vaccination in Participants Aged Between 6 to <18 Years [ Time Frame: Day 1 up to Day 7 ]
  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).
• Percentage of Participants Reporting Pre-Specified Local Reactions Within 14 Days After Vaccination in Participants Aged Between 18 to <65 Years [ Time Frame: Day 1 up to Day 14 ]
  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).
• 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 [ Time Frame: Day 1 up to Day 7 ]
  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).
• 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 [ Time Frame: Day 1 up to Day 14 ]
  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).
• Percentage of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: signing of informed consent form (Day 1) up to Day 43 ]
  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.

Original Primary Outcome Measures (submitted: June 20, 2018)

• Percentage of subjects reporting local reactions within 7days for subjects aged 6 to 17 years or 14 days for subjects aged 18 to 64 years after vaccination (redness, swelling, and pain at injection site). [ Time Frame: Day 1-7 for subjects aged 6 to 17 years or Day 1-14 for subjects aged 18 to 64 years ]
• Percentage of subjects reporting systemic events within 7days for subjects aged 6 to 17 years or 14 days for subjects aged 18 to 64 years after vaccination (fever, fatigue, headache, vomiting, diarrhea, muscle pain, joint pain). [ Time Frame: Day 1-7 for subjects aged 6 to 17 years or Day 1-14 for subjects aged 18 to 64 years ]
• Percentage of subjects reporting adverse events (AEs) within 1 month after vaccination. [ Time Frame: 1 month after vaccination ]
• Percentage of subjects reporting serious adverse events (SAEs) within 1 month after vaccination. [ Time Frame: 1 month after vaccination ]

Current Secondary Outcome Measures (submitted: November 20, 2019)

• Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at Pre-vaccination and 1 Month After Vaccination [ Time Frame: 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.
• Geometric Mean Fold Rises (GMFRs) in Serotype-specific OPA Titers 1 Month After Vaccination [ Time Frame: Pre-vaccination to 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.
• Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) at Pre-vaccination and 1 Month After Vaccination [ Time Frame: 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.
• GMFRs in Serotype-specific IgG From Before Vaccination to 1 Month After Vaccination [ Time Frame: Pre- 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.

Original Secondary Outcome Measures (submitted: June 20, 2018)

• Pneumococcal serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) measured 1 month after vaccination. [ Time Frame: 1 month after vaccination ]
• Pneumococcal serotype-specific OPA geometric mean fold rises (GMFRs) measured from before vaccination to 1 month after vaccination. [ Time Frame: 1 month after vaccination ]
• Pneumococcal serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) measured 1 month after vaccination. [ Time Frame: 1 month after vaccination ]
• Pneumococcal serotype-specific IgG geometric mean fold rises (GMFRs) measured from before vaccination to 1 month after vaccination. [ Time Frame: 1 month after vaccination ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety And Immunogenicity Study Of A 13-valent Pneumococcal Conjugate Vaccine In Japanese Subjects Aged 6 To 64 Years.
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Pneumococcal Infections

Intervention

Biological: 13-valent pneumococcal conjugate vaccine

A single dose (0.5 mL) will be administered intramuscularly into the deltoid muscle at visit 1.

Other Name: 13vPnC

Study Arms

Experimental: 13-valent pneumococcal conjugate vaccine

Intervention: Biological: 13-valent pneumococcal conjugate vaccine

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2019): 206
• Original Estimated Enrollment (submitted: June 20, 2018): 200
• Actual Study Completion Date: November 16, 2018
• Actual Primary Completion Date: November 16, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 64 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03571607
• Other Study ID Numbers: B1851172; 2018-003054-24 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2020