20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study of a 3-Dose Series in Healthy Infants

Study Overview
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Brief Summary
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20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study of a 3-Dose Series in Healthy Infants

Official Title
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A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN AS A SERIES OF 2 INFANT DOSES AND 1 TODDLER DOSE IN HEALTHY 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: Male or female infants born at >36 weeks of gestation and 2 months of age 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. 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. Previous vaccination with any licensed or investigational pneumococcal vaccine, or planned receipt through study participation.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 112 Days

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<br>Pneumococcal conjugate vaccine | Biological: 20-valent pneumococcal conjugate vaccine<br>* 20-valent pneumococcal conjugate vaccine<br>|
| Active Comparator: 13-valent pneumococcal conjugate vaccine<br>Pneumococcal conjugate vaccine | Biological: 13-valent pneumococcal conjugate vaccine<br>* 13-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 Within 7 Days After Dose 1 | Local reactions included redness, swelling and, pain at the injection site, recorded by parent's/legal guardians of participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95 percent (%) confidence interval (CI) was based on Clopper and Pearson method. | Within 7 days after Dose 1 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 2 | Local reactions included redness, swelling and, pain at the injection site, recorded by parent's/legal guardians of participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. | Within 7 days after Dose 2 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 3 | Local reactions included redness, swelling and, pain at the injection site, recorded by parent's/legal guardians of participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0 to 2.0 cm), moderate (> 2.0 to 7.0 cm) and severe (>7.0 cm). Pain at injection site was graded as mild (hurt if gently touched example, whimpered, winced, protested, or withdrew), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). 95% CI was based on Clopper and Pearson method. | Within 7 days after Dose 3 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 1 | Systemic events included fever, decreased appetite, drowsiness/increased sleep and irritability, recorded by parents/legal guardians of participant's using an e-diary. Fever was defined as temperature >=38.0 degrees Celsius (C) and categorized as >=38.0 to 38.4 degrees C, >38.4 to 38.9 degrees C, >38.9 to 40.0 degrees C and >40.0-degrees 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 was graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). 95% CI was based on Clopper and Pearson method. | 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, irritability and were recorded by using an electronic diary. Fever was defined as greater than >=38.0 degrees C and categorized to >=38.0 to 38.4 degrees C, >38.4 to 38.9 degrees C, >38.9 to 40.0 degrees C and >40.0 degrees 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 (disabled, not interested in usual daily activity). Irritability was graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable; crying could not be comforted). 95% CI was based on Clopper and Pearson method. | 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, irritability and were recorded by using an electronic diary. Fever was defined as >=38.0 degrees C and categorized to >=38.0 to 38.4 degrees C, >38.4 to 38.9 degrees C, >38.9 to 40.0 degrees C and >40.0 degrees 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 (disabled, not interested in usual daily activity). Irritability was graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable; crying could not be comforted). 95% CI was based on Clopper and Pearson method. | Within 7 Days after Dose 3 | 
| Percentage of Participants With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 2 | 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. 95% CI was based on the Clopper and Pearson method. AEs reported in this outcome measure excluded local reactions and systemic events. | From Dose 1 to 1 month after Dose 2 | 
| Percentage of Participants With Adverse Events (AEs) From Dose 3 to 1 Month After Dose 3 | 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. 95% CI was based on the Clopper and Pearson method. AEs reported in this outcome measure excluded local reactions and systemic events. | From Dose 3 to 1 month after Dose 3 | 
| Percentage of Participants With Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 1 | An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. 95% CI was based on the Clopper and Pearson method. | From Dose 1 to 1 month after Dose 1 | 
| Percentage of Participants With Newly Diagnosed Chronic Medical Condition (NDCMC) From Dose 1 to 1 Month After Dose 3 | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects. 95% CI was based on the Clopper and Pearson method. | From Dose 1 to 1 month after Dose 3 | 
| Percentage of Participants With Predefined Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After Dose 2 | Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method. | 1 month after Dose 2 | 
| Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 2 | Pneumococcal serotype-specific IgG concentrations were measured for serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and 7 additional serotypes: 8, 10A, 11A, 12F, 15B, 22F, 33F. GMCs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding 2-sided 95% CIs (based on the Student's t distribution). GMRs were reported in statistical analysis section and were calculated by exponentiating the mean logarithm of the concentrations and the corresponding 2-sided 95% CIs (based on the Student's t distribution). | 1 month after Dose 2 | 
| GMC of Serotype-specific Pneumococcal IgG Antibody 1 Month After Dose 3 | Pneumococcal serotype-specific IgG concentrations were measured for serum samples for 13vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and additional serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. GMCs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding 2-sided 95% CIs (based on the Student's t distribution). | 1 month after Dose 3 | 
| Percentage of Participants With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 3 | Vaccines administered concomitantly with 20vPnC or 13vPnC, responses assessed using pre-defined levels as follows: Diphtheria and tetanus toxoids: concentration (conc.) of antibody (in international units [IU]) to diphtheria and tetanus toxoid (prespecified level >= 0.1 IU/mL); Acellular pertussis IgG conc. of pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) (prespecified level>=observed anti-pertussis antibody concentration achieved by 95% of 13vPnC recipients); Hepatitis B: conc. of hepatitis B antibody (in milli-IU per mL [mIU/mL]) (prespecified level >=10mIU/mL); Poliomyelitis: neutralizing antibody (NA) titers to poliovirus types 1, 2, and 3 (prespecified level NA titer >= 1:8); and Haemophilus influenzae type b (Hib): conc. of antibody to Hib (polyribosylribitol phosphate [PRP]) in mcg/mL (prespecified level >=0.15 mcg/mL anti-PRP). 2-sided 95% CI based on Clopper and Pearson method. Assays were performed on randomly selected subsets. | 1 month after Dose 3 | 
| GMC of Measles Virus Antibody 1 Month After Dose 3 | Pre-specified vaccine antigen (measles) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t distribution). The assays were performed on randomly selected subsets. | 1 month after Dose 3 | 
| GMC of Mumps Virus Antibody 1 Month After Dose 3 | Pre-specified vaccine antigen (mumps) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t distribution). The assays were performed on randomly selected subsets. | 1 month after Dose 3 | 
| GMC of Rubella Virus Antibody 1 Month After Dose 3 | Pre-specified vaccine antigen (rubella) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t distribution). The assays were performed on randomly selected subsets. | 1 month after Dose 3 | 
| GMC of Varicella Virus Antibody 1 Month After Dose 3 | Pre-specified vaccine antigen (varicella) was administered concomitantly with 20vPnC or 13vPnC at Dose 3 and responses measured 1 month after Dose 3. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in the analysis. GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student's t distribution). The assays were performed on randomly selected subsets. | 1 month after Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Predefined Pneumococcal IgG Antibody 1 Month After Dose 3 | Predefined IgG concentrations were as follows: for serotype 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, 33F: >=0.35 microgram per mL (mcg/mL), for serotype 5: >=0.23 mcg/mL, for serotype 6B. >=0.10 mcg/mL and for serotype 19A: >=0.12 mcg/mL. 95% CI was based on the Clopper and Pearson method. | 1 Month after Dose 3 | 
| Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 2 | OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of participants at 1 month after Dose 2. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. | 1 month after Dose 2 | 
| GMTs of Serotype-specific Opsonophagocytic Activity (OPA) 1 Month After Dose 3 | OPA titers for the 20 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F, and 33F) were determined in randomly selected subsets of participants at 1 month after Dose 3. Results were expressed as OPA titers. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs based on the Student's t distribution. OPA titers performed on randomly selected subsets. | 1 Month after Dose 3 | 
| Geometric Mean Fold Rise (GMFRs) of IgG Concentrations From Before Dose 3 to 1 Month After Dose 3 | 20vPnC serotypes included: 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 in the analysis. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student's t distribution). | 1 month after Dose 3 | 
| Percentage of Participants With Predefined Antibody Levels for Concomitant Vaccine Antigens 1 Month After Dose 2 | Pre-specified vaccines were administered concomitantly with 20vPnC or 13vPnC and responses assessed using pre-defined levels as follows: Diphtheria and tetanus toxoids: concentration (conc.) of antibody(in international units [IU]) to diphtheria and tetanus toxoid(prespecified level >= observed anti-pertussis antibody concentration achieved by 95% of 13vPnC recipients); Poliomyelitis: NA titers to poliovirus types 1, 2, and 3 (prespecified level NA titer >=1:8); and Hib: concentration of antibody to Hib (PRP) in mcg/mL (prespecified level >=0.15 mcg/mL anti-PRP). 2-sided 95% CI was based on Clopper and Pearson method. The assays were performed on randomly selected subsets. | 1 month after Dose 2 |