Study Evaluating 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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This study is to evaluate the safety, tolerability and immunogenicity of 13-valent pneumococcal Conjugate Vaccine in children with Sickle Cell Disease who have already been vaccinated with 23-valent polysaccharide vaccine. The study will measure the amount of antibodies (the proteins that fight off germs) produced by children with Sickle Cell Disease after they have been given the 13-valent pneumococcal vaccine between 6 and less than 18 years of age. They will be given the vaccination twice, each vaccination separated by approximately 6 months.

Official Title
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A Phase 3, Open-Label, Single-Arm Trial Evaluating the Safety, Tolerability, and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Children With Sickle Cell Disease Previously Immunized With 23vPS Vaccine

Conditions
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Pneumococcal Conjugate Vaccine

Intervention / Treatment
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* Biological: 13-valent Pneumoccocal Conjugate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject between the ages of >=6 to <18 years. Diagnosis of SCD 23vPS vaccination at least 6 months prior to enrollment. Exclusion Criteria: Previous vaccination with pneumococcal conjugate vaccine. Previous reaction to any vaccine or vaccine-related component or contraindication to vaccination with pneumococcal conjugate vaccine.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: 13-valent Pneumoccocal Conjugate Vaccine<br>* 2 doses of 13vPnC will be administered by intramuscular injection separated by approximately 6 months.<br>* Other names: 13vPnC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 1 Month After 13vPnC Dose 1 to 1 Month After 13vPnC Dose 2 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 1 to 1 month after 13vPnC Dose 2 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both 1 month after 13vPnC Dose 1 and after 13vPnC Dose 2 blood draws. Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with a determinate IgG antibody concentration for the given serotype at both 1 Month After 13vPnC Dose 1 and 1 Month After 13vPnC Dose 2 blood draws. Participants may be represented in more than 1 category. | 1 Month After 13vPnC Dose 1, 1 Month After 13vPnC Dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 1 were computed using the logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from before 13vPnC Dose 1 and 1 month after 13vPnC Dose 1 blood draws. Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with determinate IgG antibody concentration for the given serotype at both the before 13vPnC Dose 1 and 1 month after 13vPnC Dose 1 blood draws. Participants may be represented in more than 1 category. | Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1 | 
| Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 2 to 1 Month After 13vPnC Dose 2 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 2 to 1 month after 13vPnC Dose 2 were computed using the logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with determinate IgG antibody concentration for the given serotype at both the before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Participants may be represented in more than 1 category. | Before 13vPnC Dose 2, 1 month after 13vPnC Dose 2 | 
| Ratio of Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 13vPnC Dose 1 to 13vPnC Dose 2 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were computed using the logarithmically transformed assay results for Dose 1 (after Dose 1/before Dose 1) and for Dose 2 (after Dose 2/before Dose 2). CI for the ratio of GMFR (Dose 2/Dose 1) were back transformations of a CI based on the Student t distribution for the mean logarithm of the measures (Dose 2 - Dose 1). Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with determinate IgG antibody concentration for given serotype at before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Participants may be represented in more than 1 category. | Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2 | 
| Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody | Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for the specified blood draw. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with determinate IgG antibody concentration for the given serotype at specified time point. Participants may be represented in more than 1 category. | Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2 | 
| Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Year After 13vPnC Dose 2 | Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for the specified blood draw. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Here number of participants analyzed signifies the evaluable immunogenicity population at 1-year follow-up and N signifies participants with determinate IgG antibody concentration for the given serotype. Participants may be represented in more than 1 category. | 1 year after 13vPnC Dose 2 | 
| Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) | Antibody GMTs as measured by OPA assay for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMT and corresponding 2-sided 95% CIs were evaluated. CIs for the GMTs are back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. GMTs were calculated using all participants with available data for the specified blood draw. Here number of participants analyzed signifies the evaluable immunogenicity population and N signifies participants with determinate OPA antibody titer for the given serotype at specified time point. Participants may be represented in more than 1 category. | Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2 | 
| Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Year After 13vPnC Dose 2 | Antibody GMTs as measured by OPA assay for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMT and corresponding 2-sided 95% CIs were evaluated. CIs for the GMTs are back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. GMTs were calculated using all participants with available data for the specified blood draw. Here number of participants analyzed signifies the evaluable immunogenicity population at 1-year follow-up and N signifies participants with determinate OPA antibody titer for the given serotype. Participants may be represented in more than 1 category. | 1 year after 13vPnC Dose 2 |