Study Evaluating the Impact of the 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children.

• ClinicalTrials.gov Identifier: NCT00743652
• Recruitment Status: Completed
• First Posted: August 29, 2008
• Results First Posted: February 10, 2012
• Last Update Posted: March 15, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This study is to evaluate the safety, immunogenicity and impact of 13-valent Pneumococcal conjugate vaccine in Alaskan Native Children.

Condition or disease	Intervention/treatment	Phase
Pneumococcal Disease; 13-valent Pneumococcal Vaccine	Biological: 13-valent Pneumococcal Conjugate Vaccine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 373 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Open Label Trial Evaluating the Safety, Immunogenicity and Impact of 13-valent Pneumococcal Conjugate Vaccine in Alaskan Native Children.
• Study Start Date: January 2009
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group1; Subjects 6 weeks to <10 months of age with 0 prior dose of Prevnar.	Biological: 13-valent Pneumococcal Conjugate Vaccine; 4 doses of 13vPnC (0.5ml, IM) will be administered. (3 doses infant series, and 1 toddler dose)
Experimental: Group 2; Subjects <12 months of age with 1 prior dose of Prevnar.	Biological: 13-valent Pneumococcal Conjugate Vaccine; 3 doses of 13vPnC (0.5ml, IM) will be administered. (2 doses for infant series catch-up, and 1 toddler dose)
Experimental: Group 3; Subjects <12 months of age with 2 prior doses of Prevnar.	Biological: 13-valent Pneumococcal Conjugate Vaccine; 2 doses of 13vPnC (0.5ml, IM) will be administered. (1 dose infant series catch-up, and 1 toddler dose)
Experimental: Group 4; Subjects ≥12 months to <2 years of age.	Biological: 13-valent Pneumococcal Conjugate Vaccine; 2 doses of 13vPnC (0.5ml, IM) will be administered. (2 catch-up dose(s) greater than 60 days apart )
Experimental: Group 5; Subjects ≥2 years to <5 years of age	Biological: 13-valent Pneumococcal Conjugate Vaccine; 1 dose of 13vPnC (0.5ml, IM) will be administered. (1 catch-up dose)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2 and 3 achieving predefined antibody threshold ≥0.35 mcg/mL along with the corresponding 95% confidence interval (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. Exact 2-sided CI based upon the observed proportion of participants.
2. Percentage of Participants Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥0.35 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
3. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Relevant Catch-Up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
   Percentage of participants in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥0.35 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.

Secondary Outcome Measures :

1. Percentage of Participants Achieving Serum IgG Antibody Level ≥0.35 Mcg/mL Prior to Vaccination With 13vPnC (Groups 4 and 5 Only) [ Time Frame: 28 to 56 days before vaccination 2 for Group 4, and before the single vaccination in Group 5. ]
   Percentage of participants in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥0.35 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
2. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥1.0 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
3. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥1.0 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
4. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
   Percentage of participants in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥1.0 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
5. Percentage of Participants Reporting Pre-Specified Local Reactions: Catch-up Dose 1 [ Time Frame: Day 1 through Day 7 after vaccination 1 for Group 4 and after the single vaccination in Group 5. ]
   Local reactions were reported by the parent/legal guardian using a diary card. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may have been represented in more than 1 category.
6. Percentage of Participants Reporting Pre-Specified Local Reactions: Catch-up Dose 2 [ Time Frame: Day 1 through Day 7 after vaccination 2 for Group 4 ]
   Local reactions were reported by the parent/legal guardian using a diary card. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may have been represented in more than 1 category.
7. Percentage of Participants Reporting Pre-Specified Systemic Events: Catch-up Dose 1 [ Time Frame: Day 1 through Day 7 after vaccination 1 for Group 4 and after the single vaccination in Group 5. ]
   Systemic events (any fever 38 degrees Celsius [C] or higher, decreased appetite, irritability, increased sleep, decreased sleep, hives [urticaria], and use of antipyretic medication) were reported using a diary card. Participants may have been represented in more than 1 category.
8. Percentage of Participants Reporting Pre-Specified Systemic Events: Catch-up Dose 2 [ Time Frame: Day 1 through Day 7 after vaccination 2 for Group 4 ]
   Systemic events (any fever 38 degrees C or higher, decreased appetite, irritability, increased sleep, decreased sleep, hives [urticaria], and use of antipyretic medication) were reported using a diary card. Participants may have been represented in more than 1 category.

Other Outcome Measures:

1. Number of Cases of Invasive Pneumococcal Disease (IPD) in Participants Less Than 5 Years of Age Due to Any Serotype Contained in 13vPnC [ Time Frame: Baseline to 6 months after last vaccination ]
   In order to assess the impact of 13vPnC on the incidence of IPD in the Yukon Kuskokwim (YK) Delta region, the Centers for Disease Control and Prevention (CDC) Arctic Investigation Program (AIP) accessed IPD data through evaluation of ongoing statewide IPD surveillance in Alaska. The CDC's AIP followed IPD (including serotype and vaccination history) to show whether identified cases of IPD received Prevnar, 13vPnC, or both. These data were combined with statewide data and used to identify the overall trend in IPD in the YK Delta region after introduction of 13vPnC.
2. Percentage of Participants Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥0.15 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
3. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥0.15 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
4. Percentage of Participants Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
   Percentage of participants in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥0.15 mcg/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. Exact 2-sided CI based upon the observed proportion of participants.
5. Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
   Antibody GMCs (mcg/mL) 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. GMC (13vPnC) with 2-sided 95% CIs were evaluated. CIs are back transformations of confidence levels based on Student t distribution for mean logarithm of concentrations. GMCs were calculated using all participants with available data for specified blood draw.
6. GMC for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, after vaccination 2 for Group 3. ]
   Antibody GMCs (mcg/mL) 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). GMC (13vPnC) with 2-sided 95% CIs were evaluated. CIs are back transformations of confidence levels based on Student t distribution for mean logarithm of concentrations. GMCs were calculated using all participants with available data for specified blood draw.
7. GMC for Serotype-specific Pneumococcal IgG Antibodies 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
   Antibody GMCs (mcg/mL) 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. GMC (13vPnC) with 2-sided 95% CIs were evaluated. CIs are back transformations of confidence levels based on Student t distribution for mean logarithm of concentrations. GMCs were calculated using all participants with available data for specified blood draw.
8. Percentage of Participants Achieving Opsonophagocytic Assay (OPA) Titers ≥Lower Limit of Quantitation (LLOQ) Measured 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2, and 3 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of participants. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis.
9. Percentage of Participants Achieving OPA Titers ≥LLOQ Measured 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3. ]
   Percentage of participants in 13vPnC Groups 1, 2 and 3 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of participants. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis.
10. Percentage of Participants Achieving OPA Titers ≥LLOQ Measured 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
    Percentage of participants in 13vPnC Groups 4 and 5 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of participants. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis.
11. Pneumococcal OPA Geometric Mean Titers (GMTs) 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
    Antibody geometric mean titers as measured by OPA assay 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). GMTs were calculated using all participants with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers.
12. Pneumococcal OPA GMTs 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, after vaccination 2 for Group 3. ]
    Antibody geometric mean titers as measured by OPA assay 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). GMTs were calculated using all subjects with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers.
13. Pneumococcal OPA GMTs 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]
    Antibody geometric mean titers as measured by OPA assay for 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMTs were calculated using all participants with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers.
14. Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Infant Series [ Time Frame: 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. ]
15. Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Toddler Dose [ Time Frame: 28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3. ]
16. Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Relevant Catch-up Dose [ Time Frame: 28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5. ]

Eligibility Criteria

• Ages Eligible for Study: 42 Days to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female infants 6 weeks to < 5years of age in good health, available for the entire study period and reachable by phone, parents able to complete all relevant study procedures.
• Infants who have received Prevnar are eligible to participate, but this is not required.
• Infants participating in the blood draws must live in a specific identified area (Yukon Kuskokwim Delta region)

Exclusion Criteria:

• Contraindication to vaccination with pneumococcal vaccine or allergic reaction to any vaccines or vaccine related components, immune deficiency, bleeding disorder or major known congenital malformation.

Contacts and Locations

Locations

United States, Alaska

Pfizer Investigational Site

Akiak, Alaska, United States, 99552

Pfizer Investigational Site

Bethel, Alaska, United States, 99559

Pfizer Investigational Site

Chefornak, Alaska, United States, 99561

Pfizer Investigational Site

Chevak, Alaska, United States, 99563

Pfizer Investigational Site

Eek, Alaska, United States, 99578

Pfizer Investigational Site

Emmonak, Alaska, United States, 99581

Pfizer Investigational Site

Hooper Bay, Alaska, United States, 99604

Pfizer Investigational Site

Kasigluk, Alaska, United States, 99609

Pfizer Investigational Site

Kongiganak, Alaska, United States, 99545

Pfizer Investigational Site

Kotlik, Alaska, United States, 99620

Pfizer Investigational Site

Kwethluk, Alaska, United States, 99621

Pfizer Investigational Site

Kwigillingok, Alaska, United States, 99622

Pfizer Investigational Site

Mtn. Village, Alaska, United States, 99632

Pfizer Investigational Site

Napaskiak, Alaska, United States, 99559

Pfizer Investigational Site

Newtok, Alaska, United States, 99559

Pfizer Investigational Site

Nunapitchuk, Alaska, United States, 99641

Pfizer Investigational Site

Russian Mission, Alaska, United States, 99657

Pfizer Investigational Site

Scammon Bay, Alaska, United States, 99662

Pfizer Investigational Site

Toksook Bay, Alaska, United States, 99637

Pfizer Investigational Site

Tuluksak, Alaska, United States, 99679

Pfizer Investigational Site

Upper Kalskag, Alaska, United States, 99607

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00743652
• Other Study ID Numbers: 6096A1-3010; B1851009
• First Posted: August 29, 2008
• Results First Posted: February 10, 2012
• Last Update Posted: March 15, 2012
• Last Verified: March 2012

Keywords provided by Pfizer:

13 valent Pneumococcal Conjugate Vaccine; Antibody Response; safety; Alaskan Native Children

Additional relevant MeSH terms:

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs