Study Evaluating a 13-valent Pneumococcal Conjugate Vaccine in Infants

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

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.

Study Overview

• Status: Completed
• Conditions: Vaccines, Pneumococcal
• Intervention / Treatment: Biological: 13-valent pneumococcal conjugate vaccine; Biological: 7 valent pneumococcal conjugate vaccine

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Campania
    • Napoli, Campania, Italy, 80122
    • Napoli, Campania, Italy, 80139
  • Emilia Romagna
    • Bologna, Emilia Romagna, Italy, 40138
  • Lazio
    • Roma, Lazio, Italy, 00165
    • Roma, Lazio, Italy, 00100
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Milan, Lombardia, Italy, 20122
  • Piemonte
    • Novara, Piemonte, Italy, 28100
  • Puglia
    • Taranto, Puglia, Italy, 74100
  • Sardegna
    • Sassari, Sardegna, Italy, 07100
  • Sicilia
    • Ragusa, Sicilia, Italy, 97100
  • Sicillia
    • Palermo, Sicillia, Italy, 90100
  • Toscana
    • Firenze, Toscana, Italy, 50132

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Aged 3 months (75 to 105 days) at time of enrollment.
2. Available for entire study period and whose parent(s)/legal guardian(s) could be reached by telephone.
3. Healthy infant, as determined by medical history, physical examination, and judgment of the investigator.
4. 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.
5. Parent(s)/legal guardian(s) had to be able to complete all relevant study procedures during study participation.

Exclusion criteria:

1. Previous vaccination with licensed or investigational pneumococcal vaccine.
2. Previous vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, or hepatitis B vaccines.
3. A previous anaphylactic reaction to any vaccine or vaccine-related component.
4. Contraindication to vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, or hepatitis B, or pneumococcal vaccines.
5. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
6. Known or suspected immune deficiency or suppression.
7. History of culture-proven invasive disease caused by S pneumoniae or Hib.
8. Major known congenital malformation or serious chronic disorder.
9. 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.
10. Receipt of blood products or gamma-globulin (including hepatitis B immunoglobulin and monoclonal antibodies; eg, Synagis® [MedImmune]).
11. Participation in another investigational trial. Participation in purely observational studies was acceptable.
12. Infant who was a direct descendant (eg, child or grandchild) of the study site personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 13-valent pneumococcal conjugate vaccine	Biological: 13-valent pneumococcal conjugate vaccine; Single 0.5 mL dose of 13vPnC given at 3, 5 and 11 months of age.
Active Comparator: 2; 7-valent pneumococcal conjugate vaccine	Biological: 7 valent pneumococcal conjugate vaccine; Single 0.5 mL dose of 7vPnC given at 3, 5 and 11 months of age.

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose	Percentage of subjects 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. (This is not a geometric mean comparison as suggested by the table row heading).	one month after infant series dose 2 and after the toddler dose
Geometric Mean Antibody Titer (OPA) in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose	Antibody functionality/geometric mean titer (GMT) as measured by opsonophagocytic activity assay(OPA) for7 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 and after the toddler dose

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Rodgers GL, Esposito S, Principi N, Gutierrez-Brito M, Diez-Domingo J, Pollard AJ, Snape MD, Martinon-Torres F, Gruber WC, Patterson S, Thompson A, Gurtman A, Paradiso P, Scott DA. Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule. Vaccine. 2013 Oct 1;31(42):4765-74. doi: 10.1016/j.vaccine.2013.08.009. Epub 2013 Aug 16.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: August 17, 2006
• First Submitted That Met QC Criteria: August 18, 2006
• First Posted (Estimate): August 21, 2006

Study Record Updates

• Last Update Posted (Estimate): February 22, 2013
• Last Update Submitted That Met QC Criteria: January 17, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Vaccine; Infants
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 6096A1-500