Study Evaluating a 13-valent Pneumococcal Conjugate Vaccine in Infants

Study Overview
=================
Brief Summary
-----------------
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 vaccinations in Italy.

Official Title
-----------------
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 Paediatric Vaccinations in Italy

Conditions
-----------------
Vaccines, Pneumococcal

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Aged 3 months (75 to 105 days) at 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. Born at greater than 32 weeks gestational age and greater than 2000 grams. Regardless of gestational age and birth weight, all subjects must have met inclusion criterion number 3. 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 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 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. 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® [MedImmune]). 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
-----------------
Minimum Age: 75 Days
Maximum Age: 105 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 0.5 mL dose of 13vPnC given at 3, 5 and 11 months of age.<br>|
| Active Comparator: 2<br>7-valent pneumococcal conjugate vaccine | Biological: 7 valent pneumococcal conjugate vaccine<br>* Single 0.5 mL dose of 7vPnC given at 3, 5 and 11 months of age.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Pre-Specified Local Reactions | Local reactions were collected using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Swelling and redness were scaled as Any (swelling or redness present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (>7.0 cm). Participants may be represented in more than 1 category. | During the 4-day period after each dose | 
| Percentage of Participants Reporting Pre-Specified Systemic Events | Systemic events (fever ≥ 37.5 degrees Celsius [C], fever ≥ 38 C but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C, decreased appetite, irritability, increased sleep, decreased sleep, hives, use of medication (meds) to treat symptoms, and use of medication to prevent symptoms) were reported using an electronic diary. Participants may be represented in more than 1 category. | During the 4-day period after each dose | 
| Percentage of Participants Achieving Predefined Antibody Levels for Concomitant Antigen Pertussis, Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus and Polio After the 2-Dose Infant Series and After the Toddler Dose | Percentage of Participants achieving predefined antibody threshold levels for Pertussis Toxoid (PT) ≥5 ELISA units per milliliter (EU/mL), Filamentous Haemagglutinin (FHA) ≥5 or ≥7.82 EU/mL, and Pertactin (PRN) ≥5 EU/mL, ≥10.0 Milli-International Units Per Milliliter (mIU/mL) for Hepatitis B, Haemophilus Influenzae type b (Hib) 0.15 μg/ml, 0.01 or 0.1 IU/mL for Diphtheria, 0.1 IU/mL for Tetanus, and ≥1:8 titer for Polio (Type 1, 2, and 3) with the corresponding 95% CI for antigens are presented. | One month after the infant series (6 months of age) and after the toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration (GMC) of Pertussis in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose | GMC of Pertussis (PT, FHA, PRN) were measured using an anti-Bordetella pertussis enzyme-linked immunosorbent assay (ELISA). Results were recorded in ELISA units per milliliter (EU/mL) | one month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration (GMC) for Hepatitis B in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After Toddler Dose | GMC of anti-hepatitis B surface antigen (HBsAg)using an Food and Drug Administration (FDA) approved in vitro diagnostic kit. | One month after the infant series (6 months of age) and the toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration (GMC) of Haemophilus Influenzae Type b (Hib) in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose | GMC for Hib polyribosylribitol phosphate as measured by ELISA, expressed in micrograms per milliliter (μg/mL). | one month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration (GMC) of Diptheria and Tetanus in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose | GMC of anti-diphtheria and anti-tetanus toxoids as measured by ELISA (IU/mL). | one month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age) | 
| Geometric Mean Antibody Concentration (GMC) of Polio Types 1, 2, and 3 in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose | GMC of Polio as measured using a polio in vitro plaque neutralization. | one month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age) | 
| Percentage of Participants Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Group After the 2-Dose Infant Series and Before the Toddler Dose | Percentages of Participants achieving World Health Organization (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 (6 months of age) and before the toddler dose (11 months of age) | 
| Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Group After the 2-Dose Infant Series and Before Toddler Dose | Antibody GMC 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 infant series dose 2 (6 months of age) and before the toddler dose (11 months of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Relative to the 7vPnC Group 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 the toddler dose (12 months of age) | 
| Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Relative to 7vPnC Group After the Toddler Dose | Antibody GMC 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 toddler dose (12 months of age) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Infants