13vPnC Multidose Vial Safety, Tolerability and Immunogenicity Study in Healthy Infants.

Study Overview
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Brief Summary
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This study will compare the immune responses of the infants who have been given 13vPnC in the mutidose vial formulation to the immune reponses of the infants who have been given 13vPnC in the single-dose syringe formulation. It will also evaluate the safety of 13-valent pneumococcal conjugate vaccine (13vPnC) in all infants who are vaccinated.

Official Title
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A Phase 3, Randomized, Open-label Trial To Evaluate The Safety, Tolerability And Immunogenicity Of 13-valent Pneumococcal Conjugate Vaccine Formulated In Multidose Vials Given With Routine Pediatric Vaccinations In Healthy Infants

Conditions
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Pneumococcal Vaccines

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 42 to 70 days at enrollment. Determined by medical history, physical examination, and clinical judgment to be eligible for the study Weight of 3.5 kg or greater at the time of enrollment Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal vaccine. A previous anaphylactic reaction to any vaccine or vaccine-related component. Contraindication to vaccination with pneumococcal conjugate vaccine. Receipt of blood products or gamma-globulin since birth

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multidose Vial Group<br>Subjects will receive three doses of 13-valent pneumococcal conjugate vaccine in the multidose vial formulation. Each dose is 0.5 mL | Biological: 13-valent pneumococcal conjugate vaccine<br>* Subjects will receive three doses (0.5 mL each) of 13-valent pneumococcal conjugate vaccine (multidose vial formulation) in the anterolateral thigh muscle of the left leg. Dose 1 is administered between 42 and 70 days of age, dose 2 is administered 28 to 42 days after dose 1, dose 3 is administered 28 to 42 days after dose 2.<br>|
| Active Comparator: Single-Dose Syringe Group<br>Subjects will receive three doses of 13-valent pneumococcal conjugate vaccine in the single-dose syringe formulation. Each dose is 0.5 mL | Biological: 13-valent pneumococcal conjugate vaccine<br>* Subjects will receive three doses (0.5 mL each) of 13-valent pneumococcal conjugate vaccine (single-dose syringe formulation) in the anterolateral thigh muscle of the left leg. Dose 1 is administered between 42 and 70 days of age, dose 2 is administered 28 to 42 days after dose 1, dose 3 is administered 28 to 42 days after dose 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Concentration Greater Than or Equal To (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series for Each Vaccine Group | Percentage of participants achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. Exact 2-sided confidence interval (Clopper and Pearson) based on the observed proportion of participants. Here n= participants with valid and determinate IgG concentration to the given serotype. | 1 month after the infant series | 
| Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series for Each Vaccine Group | Antibody GMC for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95% CI were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. CIs were back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the concentrations. Here n= participants with valid and determinate IgG concentration to the given serotype. | 1 month after the infant series | 
| Number of Participants Reporting Local Reaction Within 5 Days After Dose 1 in MDV and SDS Group | Local reactions were reported within 5 days (day 2 to day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (greater than [>] 7.0 cm). Participants may be represented in more than 1 category. | Within 5 days after Dose 1(Day 2 to Day 6) of the infant series | 
| Number of Participants Reporting Local Reaction Within 5 Days After Dose 2 in MDV and SDS Group | Local reactions were reported within 5 days (day 2 to day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (greater than [>] 7.0 cm). Participants may be represented in more than 1 category. | Within 5 days after Dose 2 (Day 2 to Day 6) of the infant series | 
| Number of Participants Reporting Local Reaction Within 5 Days After Dose 3 in MDV and SDS Group | Local reactions were reported within 5 days (day 2 to day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (greater than [>] 7.0 cm). Participants may be represented in more than 1 category. | Within 5 days after Dose 3 (Day 2 to Day 6) of the infant series | 
| Number of Participants Reporting Systemic Events Within 5 Days After Dose 1 in MDV and SDS Group | Systemic events (any fever greater than or equal to [>=] 38.0 degrees Celsius [C], decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Participants may be represented in more than 1 category. | Within 5 days after Dose 1 (Day 2 to Day 6) of infant series | 
| Number of Participants Reporting Systemic Events Within 5 Days After Dose 2 in MDV and SDS Group | Systemic events (any fever greater than or equal to [>=] 38.0 degrees Celsius [C], decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Participants may be represented in more than 1 category. | Within 5 days after Dose 2 (Day 2 to Day 6) of infant series | 
| Number of Participants Reporting Systemic Events Within 5 Days After Dose 3 in MDV and SDS Group | Systemic events (any fever greater than or equal to [>=] 38.0 degrees Celsius [C], decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Participants may be represented in more than 1 category. | Within 5 days after Dose 3 (Day 2 to Day 6) of infant series | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Infant Series | An AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 to 42 days after last dose that were absent before treatment or that worsened relative to pretreatment state | Dose 1 up to 28 to 42 days after dose 3 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Prior to Dose 1 | An AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse events were also reported in participants who provided consent but were not randomized in this study. The data of these participants has been reported under 'Screened Only' arm. | Informed consent up to Dose 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Serotype-Specific Opsonophagocytic Activity (OPA) Titer >= Lower Limit of Quantitation (LLOQ) 1 Month After Infant Series | Percentage of participants achieving OPA Titer >= lower limit of quantitation (LLOQ) along with 95% CI for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Exact 2-sided confidence interval (Clopper and Pearson) based on the observed proportion of participants. Here n= Number of participants with an antibody titer ≥ LLOQ for the given serotype. | 1 month after the infant series | 
| Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After the Infant Series | Antibody geometric mean titers as measured by OPA assay for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. GMTs were calculated using all participants with available data for the specified blood draw. CIs were back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. Here n= participants evaluable =specified category. | 1 month after the infant series | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevenar 13, 13vPnC, Healthy Subjects