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 Prevenar (7vPnC), when given concomitantly with routine paediatric vaccines in the United Kingdom.

Official Title
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A Phase 3, Randomized, Active-Controlled, Double-Blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Pediatric Vaccinations in the United Kingdom

Conditions
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Vaccines, Pneumococcal

Intervention / Treatment
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* Biological: 13-valent Pneumococcal Conjugate Vaccine
* Biological: 7vPnC
* Biological: Pediacel
* Biological: NeisVac-C
* Biological: Menitorix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2 months (42 to 98 days) at the time of enrollment. Available for entire study period and whose parent(s)/legal guardian(s) could be reached by telephone. Healthy infant, as determined by medical history, physical examination, and judgment of the investigator. Parent(s)/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 meningococcal vaccines. A previous anaphylactic reaction to any vaccine or vaccine-related component. Contraindication to vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, pneumococcal conjugate, or meningococcal conjugate 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, Neisseria meningitidis, or Hib. 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. This 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: 42 Days
Maximum Age: 98 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 vaccine | Biological: 13-valent Pneumococcal Conjugate Vaccine<br>* Single 0.5 mL dose given at 2, 3, 4, and 12 months of age<br>Biological: Pediacel<br>* concommitant vaccine, both at arm 1 and at arm 2, at 2 months, 3 months and 4 months of age<br>Biological: NeisVac-C<br>* concomittant vaccine, both at arm 1 and at arm 2, at 2 months and 4 months of age<br>Biological: Menitorix<br>* concomitant vaccine, both at arm 1 and at arm 2, at 12 months of age<br>|
| Active Comparator: 2<br>7-valent pneumococcal vaccine | Biological: 7vPnC<br>* Single 0.5 mL dose given at 2, 3, 4 and 12 months of age<br>Biological: Pediacel<br>* concommitant vaccine, both at arm 1 and at arm 2, at 2 months, 3 months and 4 months of age<br>Biological: NeisVac-C<br>* concomittant vaccine, both at arm 1 and at arm 2, at 2 months and 4 months of age<br>Biological: Menitorix<br>* concomitant vaccine, both at arm 1 and at arm 2, at 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 a Meningococcal C Serum Bactericidal Assay (SBA) Titer ≥1:8 and Predefined Antibody Levels for Pertussis and Haemophilus Influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series. | Percentage of participants achieving a meningococcal C SBA serum antibody titer ≥1:8 and predefined antibody threshold levels with the corresponding 95% CI for concomitant antigens polyribosylribitol phosphate (PRP) in haemophilus influenzae type b [Hib](≥0.15 μg/mL or ≥ 1.0 μg/mL), pertussis toxoid [PT], filamentous haemagglutinin, pertactin [FHA], and pertactin (PRN) (≥5 Elisa Units EU/mL) and fimbrial agglutinogens [FIM] (≥2.2 EU/mL) are presented. | One month after infant series dose 2 (5 months of age) | 
| Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series |  | one month after infant series dose 2 (5 months of age) | 
| Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series |  | one month after infant series dose 2 (5 months of age) | 
| Geometric Mean Antibody Concentration of Pertusis Filamentous Haemagglutinin (FHA), Pertussis Toxoid (PT), Pertactin (PRN), and Fimbrial Agglutinogens (FIM) as Measured by ELISA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series |  | one month after infant series dose 2 (5 months of age) | 
| Percentage of Participants in the 13vPnC Group Achieving a Serotype-specific IgG Antibody Concentration ≥0.35 µg/mL Measured 1 Month After the 2-dose Infant Series, Before and After the Toddler Dose | Percentages of participants achieving WHO predefined antibody threshold ≥0.35μg/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 infant series dose 2 (5 months of age), before and after toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration in 13vPnC Group After the 2-dose Infant Series, Before and After the Toddler Dose. | Antibody concentration/geometric mean concentration (GMC) as measured by 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 with corresponding 2-sided 95% CI. | one month after infant series dose 2 (5 months of age) and before and after toddler dose (12 months of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an SBA Titer ≥1:8 for Meningococcal C in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose. |  | one month after the toddler dose (13 months of age) | 
| Percentage of Participants Achieving a Predefined Antibody Level for Haemophilus Influenzae Type b in the 13vPnC Group Relative to the 7vPnC Group After the Toddler Dose. |  | one month after toddler dose (13 months of age) | 
| Geometric Mean Antibody Concentration for Haemophilus Influenzae Type b PRP in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose. |  | one month after toddler dose (13 months of age) | 
| Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose |  | one month after toddler dose (13 months of age) |