20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study in Healthy Japanese Infants

Study Overview
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Brief Summary
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20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study in Healthy Japanese Infants

Official Title
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A PHASE 3, RANDOMIZED, DOUBLE-BLIND, THIRD PARTY UNBLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY JAPANESE INFANTS

Conditions
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Pneumococcal Disease

Intervention / Treatment
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* Biological: 20-valent pneumococcal conjugate vaccine
* Biological: 13-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese male or female infants ≥2 months to ≤6 months at the time of consent. Healthy infants determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study. Exclusion Criteria: History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) Major known congenital malformation or serious chronic disorder. History of microbiologically proven invasive disease caused by S pneumoniae. Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20-valent pneumococcal conjugate vaccine (subcutaneous)<br>20-valent pneumococcal conjugate vaccine administered by subcutaneous injection (SC) | Biological: 20-valent pneumococcal conjugate vaccine<br>* 20-valent pneumococcal conjugate vaccine<br>|
| Active Comparator: 13-valent pneumococcal conjugate vaccine (subcutaneous)<br>13-valent pneumococcal conjugate vaccine administered by subcutaneous injection (SC) | Biological: 13-valent pneumococcal conjugate vaccine<br>* 13-valent pneumococcal conjugate vaccine<br>|
| Experimental: 20-valent pneumococcal conjugate vaccine (intramuscular)<br>20-valent pneumococcal conjugate vaccine administered by intramuscular injection (IM) | Biological: 20-valent pneumococcal conjugate vaccine<br>* 20-valent pneumococcal conjugate vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 | Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 centimeter (cm). Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm. | Within 7 Days after Dose 1 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 2 | Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm. | Within 7 Days after Dose 2 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 3 | Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm. | Within 7 Days after Dose 3 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 4 | Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm. | Within 7 Days after Dose 4 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 1 | Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature greater than or equal to (>=) 37.5 degree Celsius (C), and categorized as >=37.5 to 38.4 degree C, greater than (>)38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 1 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 2 | Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 2 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 3 | Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 3 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 4 | Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 4 | 
| Percentage of Participants With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 3 | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Day 1 of Dose 1 to 1 Month after Dose 3 | 
| Percentage of Participants With AEs From Dose 4 to 1 Month After Dose 4 | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | From Dose 4 to 1 Month after Dose 4 | 
| Percentage of Participants With Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 4 | A serious AE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. | From Dose 1 to 1 Month after Dose 4 | 
| Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Dose 1 to 1 Month After Dose 4 | An NDCMC was defined as a significant disease or medical condition, not previously identified, that is expected to be persistent or was otherwise long-lasting in its effects. | From Dose 1 to 1 Month after Dose 4 | 
| Percentage of Participants With Predefined Pneumococcal Serotype-specific Immunoglobulin G (IgG) Concentrations 1 Month After Dose 3 | Pneumococcal serotype-specific IgG Concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. The predefined levels, >=0.35 micrograms/mL for all serotypes except for serotypes 5 (>=0.23 micrograms/mL), 6B (>=0.10 micrograms/mL) and 19A (>=0.12 micrograms/mL). | 1 Month after Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration of Pneumococcal Serotype-Specific IgG Concentrations 1 Month After Dose 3 | Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. Assay results below the LLOQ were set to 0.5*LLOQ. | 1 Month after Dose 3 | 
| Geometric Mean Concentration of Pneumococcal Serotype-Specific IgG Concentrations 1 Month After Dose 4 | Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. | 1 Month after Dose 4 | 
| Geometric Mean Titer (GMTs) of Serotype Specific Opsonophagocytic Activity (OPA) at 1 Month After Dose 3, Before Dose 4 and 1 Month After Dose 4 | 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. OPA titers were determined in randomly selected subsets of sera from each vaccine group. | 1 Month after Dose 3, before Dose 4 and 1 Month after Dose 4 | 
| Percentage of Participants With Pre-defined Pneumococcal Serotype-specific IgG Concentrations at 1 Month After Dose 4 | Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The predefined levels, >=0.35 micrograms/mL for all serotypes except for serotypes 5 (>=0.23 micrograms/mL), 6B (>=0.10 micrograms/mL) and 19A (>=0.12 micrograms/mL). | 1 Month after Dose 4 | 
| Geometric Mean Fold Rise (GMFR) in Serotype-Specific IgG Concentrations From 1 Month After Dose 3 to Before Dose 4 | GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from 1 month after Dose 3 to before Dose 4 was reported from participants in Dose 3 evaluable immunogenicity population. | 1 Month after Dose 3 to before Dose 4 | 
| GMFR in Serotype-Specific IgG Concentrations From 1 Month After Dose 3 to 1 Month After Dose 4 | GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from 1 month after Dose 3 to 1 month after Dose 4 was reported from participants in both the Dose 3 and Dose 4 evaluable immunogenicity population. | From 1 Month after Dose 3 to 1 Month after Dose 4 | 
| GMFR in Serotype-Specific IgG Concentrations From Before Dose 4 to 1 Month After Dose 4 | GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from before Dose 4 to 1 month after Dose 4 was reported from participants in the Dose 4 evaluable immunogenicity population. | From before Dose 4 to 1 Month after Dose 4 |