Study to Evaluate 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 Pediatric Vaccinations in the United Kingdom

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.

Study Overview

• Status: Completed
• Conditions: Vaccines, Pneumococcal
• Intervention / Treatment: Biological: 13-valent Pneumococcal Conjugate Vaccine; Biological: Pediacel; Biological: NeisVac-C; Biological: Menitorix; Biological: 7vPnC

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Atherstone, United Kingdom, CV9 1EU
  • Bangor, United Kingdom, BT19 1NB
  • Bristol, United Kingdom, BS2 8AE
  • Co Antrim, United Kingdom, BT41 3AE
  • Coventry, United Kingdom, CV6 4DD
  • Ely, United Kingdom, CB7 4HF
  • London, United Kingdom, SW17 ORE
  • Oxford, United Kingdom, OX3 9DU
  • Plymouth, United Kingdom, PL5 3JB
  • Southampton, United Kingdom, SO16 6YD
  • Weston-Super-Mare, United Kingdom, BS22 6AJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 2 months (42 to 98 days) at the 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. 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 meningococcal vaccines.
3. A previous anaphylactic reaction to any vaccine or vaccine-related component.
4. Contraindication to vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, pneumococcal conjugate, or meningococcal conjugate 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, Neisseria meningitidis, 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. This 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®).
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 vaccine	Biological: 13-valent Pneumococcal Conjugate Vaccine; Single 0.5 mL dose given at 2, 3, 4, and 12 months of age; Biological: Pediacel; concommitant vaccine, both at arm 1 and at arm 2, at 2 months, 3 months and 4 months of age; Biological: NeisVac-C; concomittant vaccine, both at arm 1 and at arm 2, at 2 months and 4 months of age; Biological: Menitorix; concomitant vaccine, both at arm 1 and at arm 2, at 12 months of age
Active Comparator: 2; 7-valent pneumococcal vaccine	Biological: Pediacel; concommitant vaccine, both at arm 1 and at arm 2, at 2 months, 3 months and 4 months of age; Biological: NeisVac-C; concomittant vaccine, both at arm 1 and at arm 2, at 2 months and 4 months of age; Biological: Menitorix; concomitant vaccine, both at arm 1 and at arm 2, at 12 months of age; Biological: 7vPnC; Single 0.5 mL dose given at 2, 3, 4 and 12 months of age

What is the study measuring?

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	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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Pre-Specified Local Reactions	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (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 (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 ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C, decreased appetite, irritability, increased sleep, decreased sleep, use of medication (Meds) to prevent symptoms, and use of medication to treat symptoms) were collected using an electronic diary; percentage of participants with each event was evaluated.	During the 4-day period after each dose

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Trial Manager, For UK/Great Britian, ukmedinfo@wyeth.com

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.
• Snape MD, Klinger CL, Daniels ED, John TM, Layton H, Rollinson L, Pestridge S, Dymond S, Galiza E, Tansey S, Scott DA, Baker SA, Jones TR, Yu LM, Gruber WC, Emini EA, Faust SN, Finn A, Heath PT, Pollard AJ. Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial. Pediatr Infect Dis J. 2010 Dec;29(12):e80-90. doi: 10.1097/inf.0b013e3181faa6be.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 2, 2006
• First Submitted That Met QC Criteria: October 2, 2006
• First Posted (Estimate): October 4, 2006

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 6096A1-007