Study to Evaluate a 13-valent Pneumococcal Conjugate Vaccine in Infants.

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and immunogenicity of a 13-valent pneumococcal conjugate (13vPnC) vaccine compared to 7-valent pneumococcal conjugate (Prevenar/Prevenar®, 7vPnC), when given concomitantly with Infanrix hexa at 2, 3, 4, months (infant series) and at 11-12 months of age (toddler dose) in Germany.

Official Title
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A Phase 3, Randomized, Active-Controlled, Double-blind Trial of the Safety, Tolerability, and Immunologic Non-Inferiority of a 13-valent Pneumococcal Conjugate Vaccine Compared to a 7-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Pediatric Vaccinations in Germany.

Conditions
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Vaccines, Pneumococcal

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine
* Biological: 7-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2 months (56 to 112 days) at time of enrollment. Available for entire study period and whose parent(s) or legal guardian(s) could be reached by telephone. Healthy infant, as determined by medical history, physical examination, and judgment of the investigator. Parent(s) or legal guardian(s) had to be able to complete all relevant study procedures during study participation. Exclusion criteria: Previous vaccination with licensed or investigational pneumococcal vaccine. Previous vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, or hepatitis B vaccines. A previous anaphylactic reaction to any vaccine or vaccine-related component. Contraindication to vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, or hepatitis B, or pneumococcal vaccines. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection. Known or suspected immune deficiency or suppression. History of culture-proven invasive disease caused by S pneumoniae or H influenzae type b. Major known congenital malformation or serious chronic disorder. Significant neurological disorder or history of seizure, including febrile seizure, or significant stable or evolving disorders, such as cerebral palsy, encephalopathy, hydrocephalus, or other significant disorders. Did not include resolving syndromes due to birth trauma such as Erb palsy. Receipt of blood products or gamma-globulin (including hepatitis B immunoglobulin and monoclonal antibodies; eg, Synagis®). Participation in another investigational trial. Participation in purely observational studies was acceptable. Infant who was a direct descendant (eg, child or grandchild) of the study site personnel.

Ages Eligible for Study
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Minimum Age: 56 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: 1<br>13-valent pneumococcal conjugate vaccine | Biological: 13-valent pneumococcal conjugate vaccine<br>* Single 0.5mL dose given at 2, 3, 4 and 11 to 12 months of age<br>|
| Active Comparator: 2<br>7-valent pneumococcal conjugate vaccine | Biological: 7-valent pneumococcal conjugate vaccine<br>* Single 0.5mL dose given at 2, 3, 4 and 11 to 12 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Antibody Level ≥0.35 μg/mL in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Percentage of Participants achieving World Health Organization (WHO) predefined antibody threshold ≥0.35 μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | One month after 3-dose infant series (5 months of age) | 
| Geometric Mean Antibody Concentration in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Antibody concentration/geometric mean concentration (GMC) as measured by enzyme-linked immunosorbent assay (ELISA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC ratios (13vPnC/7vPnC) and corresponding 2-sided 95% CI were evaluated. | One month after 3-dose infant series (5 months of age) | 
| Percentage of Participants Achieving Antibody Titer ≥1:8 as Measured by Opsonophagocytic Activity Assay (OPA) in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series. | Percentage of Participants achieving functional antibody titer ≥1:8 as measured by opsonophagocytic activity assay (OPA) along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | One month after 3-dose infant series (5 months of age) | 
| Geometric Mean Antibody Titer in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Antibody functionality/geometric mean titer (GMT) as measured by opsonophagocytic activity assay (OPA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | One month after 3-dose infant series (5 months of age) | 
| Percentage of Participants Achieving Predefined Antibody Levels for Haemophilus Influenzae Type b, Diphtheria Toxoid, and Hepatitis B in 13vPnC Group Relative to 7vPnC Group After the Infant Series and After the Toddler Dose | Predefined Antibody Levels for Haemophilus Influenzae Type b (0.15 µg/mL or 1.0 µg/mL), for Diphtheria Toxoid (0.01 or 0.1 International units [IU]/mL) and for Hepatitis B (≥ 10.0 mIU/mL). | One month after the infant series (5 months of age) ; one month after the toddler dose (13 months of age) | 
| Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the Infant Series and After the Toddler Dose |  | One month after the infant series (5 months of age) ; one month after the toddler dose (13 months of age) | 
| Geometric Mean Antibody Concentration of Diphtheria Toxoid in 13vPnC Group Relative to 7vPnC Group After the Infant Series and After the Toddler Dose |  | One month after the infant series (5 months of age) ; one month after the toddler dose (13 months of age) | 
| Geometric Mean Antibody Concentration of Hepatitis B in 13vPnC Group Relative to 7vPnC Group After the Infant Series and After the Toddler Dose | Antibody geometric mean concentration (GMC) as measured by mcg/mL for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | One month after the infant series (5 months of age) ; one month after the toddler dose (13 months of age) | 
| Geometric Mean Concentration in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose | Antibody concentration/geometric mean concentration as measured by ELISA with their corresponding 95% CI immediately before and after the toddler dose for 7 common pneumococcal serotypes (Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | Immediately before (12 months of age) and one month after the toddler dose (13 months of age) | 
| Percentage of Participants Reporting Pre-Specified Local Reactions | Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (Sig) (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (Mod)(2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category. | Day 1 through 4 after each dose | 
| Percentage of Participants Reporting Pre-Specified Systemic Events (Infant Series) | Systemic events (any fever ≥ 38 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category. | Day 1 through 4 after each dose | 
| Percentage of Participants Reporting Pre-Specified Systemic Events (Toddler Series) | Systemic events (any fever ≥ 38 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Participants may be represented in more than 1 category. | Day 1 through 4 after each dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, safety