Study Evaluating Prevnar Infant Long-term Immune Response Versus Prevnar Naive Cohort (PILOT)

Characterization of the Prevnar Infant Long-term Immune Response vs a Prevnar Naive Cohort

The purpose of this study is to assess the "late" immune response to further doses of pneumococcal conjugate vaccine more than 10 years after primary immunization with Prevnar (7vPnC) in infancy, as compared with individuals who did not receive Prevnar in infancy (the Prevnar naive cohort which received MnCC). The study will take place at a single study center. Study participants must have participated previously in a specific Wyeth Prevnar study (Study D118-P8) and must still be enrolled in the Northern California Kaiser Permanente (NCKP) health plan.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Conjugate Vaccine
• Intervention / Treatment: Biological: 13-valent Pneumococcal Conjugate Vaccine

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Hayward, California, United States, 94545
      • Pfizer Investigational Site
    • San Jose, California, United States, 95119
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Fully vaccinated per-protocol (4 doses of vaccine given at 2, 4, 6, and 12-15 months of age) subjects enrolled in the Prevnar arm of Study D118-P8, OR
• Fully vaccinated per-protocol subjects from the control arm of the same study that did not receive Prevnar after the close of Study D118-P8, or at any time following the study, AND
• Still enrolled in NCKP health plan.
• Subjects included in either group above must be in good health as determined by medical history, physical examination, and clinical judgment.

Exclusion Criteria:

• Previous receipt of pneumococcal polysaccharide vaccine.
• History of documented recurrent pneumococcal otitis media or any occurence of pneumonia within past 12 months
• History of documented invasive pneumococcal disease (defined as a positive culture of S. pneumoniae from a normally sterile body site).
• Known or suspected disease or dysfunction of the immune system, including:
• HIV infection
• Malignancy
• Receipt of immunosuppressive therapy
• Sickle cell hemoglobinopathy
• Concomitant vaccination during the study period.
• Known hypersensitivity to any component of Prevnar.
• Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study, or could preclude the evaluation of the subject's response.
• Receipt of immune globulin within the past 3 months.
• Positive pregnancy test for menarchal female subjects.
• Females who are breastfeeding.
• For control subjects, previous receipt of Prevnar at any time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Subjects received Prevnar in study D118-P8	Biological: 13-valent Pneumococcal Conjugate Vaccine; single injection, single dose, single site, 0.5 mL per dose.; Other Names: 13vPnC
Experimental: 2; Subjects received MnCC in study D118-P8	Biological: 13-valent Pneumococcal Conjugate Vaccine; single injection, single dose, single site, 0.5 mL per dose.; Other Names: 13vPnC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a Pneumococcal IgG Antibody Concentration ≥0.35 Mcg/mL for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 5)	Percentage of participants achieving predefined IgG antibody threshold ≥0.35 micrograms per milliliter (Mcg/mL) for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% confidence intervals (CIs) based on the observed percentage of participants.	Day 28 (Visit 5)
Percentage of Participants Achieving a Pneumococcal IgG Antibody Concentration ≥0.35 Mcg/mL for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 4)	Percentage of participants achieving predefined IgG antibody threshold ≥0.35 Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% CIs based on the observed percentage of participants.	Day 7 (Visit 4)
Percentage of Participants Achieving a Pneumococcal Opsonophagocytic Activity (OPA) Antibody Titer ≥LLOQ for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 5)	Percentage of participants achieving predefined OPA antibody titer ≥ serotype-specific lower limit of quantification (LLOQ) using modified microcolony assays for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% CIs based on the observed percentage of participants. LLOQ for each serotype: 1=1:8, 3=1:12, 4=1:21, 5=1:29, 6A=1:37, 6B=1:43, 7F=1:210, 9V=1:345, 14=1:35, 18C=1:31, 19A=1:18, 19F=1:48, 23F=1:13.	Day 28 (Visit 5)
Percentage of Participants Achieving a Pneumococcal Opsonophagocytic Activity (OPA) Antibody Titer ≥LLOQ for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 4)	Percentage of participants achieving predefined OPA antibody titer ≥ serotype-specific lower limit of quantification (LLOQ) using modified microcolony assays for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% CIs based on the observed percentage of participants. LLOQ for each serotype: 1=1:8, 3=1:12, 4=1:21, 5=1:29, 6A=1:37, 6B=1:43, 7F=1:210, 9V=1:345, 14=1:35, 18C=1:31, 19A=1:18, 19F=1:48, 23F=1:13.	Day 7 (Visit 4)
Percentage of Participants Achieving a Pneumococcal Opsonophagocytic Activity (OPA) Antibody Titer ≥1:8 for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 5)	Percentage of participants achieving predefined OPA antibody titer ≥1:8 for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% CIs based on the observed percentage of participants. The lowest titer that can be determined using the standard OPA assay is a titer of 1:8 limit of detection (LOD) and is the same for each serotype-specific OPA assay.	Day 28 (Visit 5)
Percentage of Participants Achieving a Pneumococcal Opsonophagocytic Activity (OPA) Antibody Titer ≥1:8 for the 13 Serotypes for 7vPnC / 13vPnC in Comparison to MnCC / 13vPnC After Vaccination (Visit 4)	Percentage of participants achieving predefined OPA antibody titer ≥1:8 for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A) along with the exact, 2-sided 95% CIs based on the observed percentage of participants. The lowest titer that can be determined using the standard OPA assay is a titer of 1:8 limit of detection (LOD) and is the same for each serotype-specific OPA assay.	Day 7 (Visit 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes Relative to 7vPnC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 5	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 28 (Visit 5)
Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes Relative to MnCC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 5	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 28 (Visit 5)
Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes Relative to 7vPnC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 4	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 7 (Visit 4)
Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes Relative to MnCC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 4	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 7 (Visit 4)
Pneumococcal Opsonophagocytic Activity (OPA) Assay Geometric Mean Titers (GMTs) for the 13 Serotypes Relative to 7vPnC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 5	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 28 (Visit 5)
Pneumococcal Opsonophagocytic Activity (OPA) Assay Geometric Mean Titers (GMTs) for the 13 Serotypes Relative to MnCC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 5	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 28 (Visit 5)
Pneumococcal Opsonophagocytic Activity (OPA) Assay Geometric Mean Titers (GMTs) for the 13 Serotypes Relative to 7vPnC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 4	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 7 (Visit 4)
Pneumococcal Opsonophagocytic Activity (OPA) Assay Geometric Mean Titers (GMTs) for the 13 Serotypes Relative to MnCC / 13vPnC Prevaccination Visit 1 and Postvaccination Visit 4	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Baseline (Visit 1), Day 7 (Visit 4)
Comparison of Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes for 7vPnC / 13vPnC Relative to MnCC / 13vPnC After Vaccination (Visit 5)	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Day 28 (Visit 5)
Comparison of Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the 13 Serotypes for 7vPnC / 13vPnC Relative to MnCC / 13vPnC After Vaccination (Visit 4)	Pneumococcal IgG GMCs measured as Mcg/mL for the 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMCs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Day 7 (Visit 4)
Comparison of Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Serotypes for 7vPnC / 13vPnC Relative to MnCC / 13vPnC After Vaccination (Visit 5)	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Day 28 (Visit 5)
Comparison of Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Serotypes for 7vPnC / 13vPnC Relative to MnCC / 13vPnC After Vaccination (Visit 4)	Antibody geometric mean titers as measured by opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes (7vPnC serotypes 4, 6B, 9V, 14, 18C, 19F, 23F and additional serotypes 1, 3, 5, 6A, 7F, and 19A). The 2-sided, 95% CIs for the GMTs were constructed by back transformation of the CIs for the mean of the logarithmically transformed assay results computed using the Student t distribution.	Day 7 (Visit 4)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Pre-specified Local Reactions Within 4 Days After Vaccination	Local reactions reported using the diary card during the 4-day reactogenicity period after vaccination. Tenderness at injection site scaled as Any (tenderness present) or Significant (present and interfered with limb movement). Redness and swelling at injection site scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); or Severe (> 7.0 cm). Participants may be represented in >1 category.	Baseline up to 4 days after vaccination on Day 1
Percentage of Participants Reporting Pre-specified Systemic Events Within 4 Days After Vaccination	Systemic events reported using the diary card during the 4-day reactogenicity period after vaccination. Temperature scaled as Fever ≥38 but ≤39 degrees Celsius (C) (mild), >39 but ≤40 degrees C (moderate), or >40 degrees C (severe). Presence of Decreased appetite, Irritability, Increased sleep, Decreased sleep, Rash, and Hives; also scaled as Mild (easily tolerated, minimal discomfort; not interfering with activities), Moderate (sufficiently discomforting to interfere with normal activities), or Severe (may prevent normal activities and require medical intervention).	Baseline up to 4 days after vaccination on Day 1

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Klein NP, Ensor K, Jouve S, Northington R, Moscariello M, McGovern PC. Long-term immune responses to pneumococcal conjugate vaccines in children previously vaccinated with 7-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2013 Sep;32(9):990-7. doi: 10.1097/INF.0b013e3182959f34.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: January 16, 2009
• First Submitted That Met QC Criteria: January 16, 2009
• First Posted (Estimate): January 19, 2009

Study Record Updates

• Last Update Posted (Estimate): November 11, 2011
• Last Update Submitted That Met QC Criteria: October 5, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: single dose; Single site; Participated in Wyeth D118-P8
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 6096A1-3016; B1851014