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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |