Study to Evaluate 13 Valent Pneumococcal Conjugate Vaccine (13vPnC) Vaccine Followed by 23-valent Pneumococcal Polysaccharide Vaccine (23vPS) Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Study Overview
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Brief Summary
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People who have received an allogeneic hematopoetic stem cell transplant (HSCT) are more likely than other people to get ill from a germ called Streptococcus pneumoniae. Most people who have had a stem cell transplant are offered a vaccine called 23-valent pneumococcal polysaccharide vaccine (23vPS) to help protect against this germ. The purpose of this study is to evaluate the immune response in HSCT recipients who receive a 13 valent pneumococcal vaccine (13vPnC) followed by 23vPS.

Official Title
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A Phase 3, Open-label Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of 13-valent Pneumococcal Conjugate Vaccine Followed By 23-valent Pneumococcal Polysaccharide Vaccine In Recipients Of Allogeneic Hematopoietic Stem Cell Transplant Aged 2 Years And Older

Conditions
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Vaccines, Pneumococcal Conjugate Vaccine

Intervention / Treatment
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* Biological: 13vPnC
* Biological: 23vPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject >=2 years of age. Allogeneic HSCT for hematologic disorder. Allogeneic HSCT with full myeloablative conditioning or reduced intensity conditioning. Allogeneic HSCT approximately 3 to 6 months (91 days to 203 days) before enrollment. Stable engraftment (absolute neutrophil count (ANC) >1000/µL; platelet count >50,000/µL). Complete hematologic remission of underlying disease with very good partial remission (VGPR) acceptable in the case of lymphoma and myeloma. Subject or parent/legal guardian expected to be available for the entire study and can be contacted by telephone. Subject or parent/legal guardian must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation. Hematological recovery as defined by ANC >1000/µL; platelet count >50,000/µL. All female and male subjects who are biologically capable of having children must agree to abstinence or commit to the use of a reliable method of birth control from signing of the ICF until for 3 months after the last vaccination. Negative urine pregnancy test for all female subjects of child bearing potential. Exclusion Criteria: Autologous HSCT. Receipt of donor lymphocyte infusions during the 28 days preceding enrollment. Uncontrolled GVHD that in the opinion of the investigator would prevent the subject from participating in the study. Lansky/Karnofsky Score <=60%. Receipt of plasma products or immunoglobulins during the 60 days preceding enrollment. Receipt of rituximab since HSCT. Receipt of chemotherapy for relapse of underlying malignant disease since HSCT. Human immunodeficiency virus (HIV) infection. Lymphoproliferative disorder since HSCT. Chronic illnesses with cardiac, pulmonary, renal, or liver failure that in the opinion of the investigator would prevent the subject participating in the study. Vaccination with any licensed or experimental pneumococcal vaccine since HSCT. Previous anaphylactic reaction to any vaccine or vaccine-related component. Bleeding diathesis or condition associated with prolonged bleeding time that would in the opinion of the investigator contraindicate intramuscular injection. Participation in another study with ongoing use of an unlicensed investigational product from 28 days before study enrollment until the end of the study. Participation in another study with ongoing use of a licensed investigational product that in the opinion of the investigator would interfere with the evaluation of the study objectives. Permanent residence in a nursing home or other residential care facility. Pregnant or breastfeeding female subject. Subject who is a direct relative (child, grandchild, parent, or grandparent) of study personnel, or is a member of the study personnel. Receipt of advanced therapy medicinal products (ATMP) including gene therapy products, somatic cell therapy products, and tissue engineered products at any time before enrollment. If information is available, - previous allergic or anaphylactic reaction to any vaccine or vaccine-related component in a stem cell donor.

Ages Eligible for Study
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Minimum Age: 2 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: 13vPnC<br>* 0.5mL 13vPnC dose will be administered intramuscularly into the left limb at visits 1,2,3 and 5. Starting 3-6 months after HSCT 3 doses given at monthly intervals. 4th dose given 6 months after 3rd dose.<br>Biological: 23vPS<br>* 0.5mL dose of 23vPS will be administered intramuscularly at visit 6. 23vPS given 1 month after 4th dose of 13vPnC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 3 in All Participants | 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 3 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 before 13vPnC Dose 1 and after 13vPnC Dose 3 blood draws. | Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 3 in Pediatric, Adult and All Participants | Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 3 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. | 1 month after 13vPnC Dose 3 | 
| Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants | Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 4 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. | 1 month after 13vPnC Dose 4 | 
| Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 3 in Pediatric and Adult Participants | 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 3 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 both before 13vPnC Dose 1 and after 13vPnC Dose 3 blood draws. | Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 3 | 
| Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants | 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 4 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 both before 13vPnC Dose 1 and after 13vPnC Dose 4 blood draws. | Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 4 | 
| Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 3 to 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants | 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 3 to 1 month after 13vPnC Dose 4 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 both after 13vPnC Dose 3 and after 13vPnC Dose 4 blood draws. | 1 month after 13vPnC Dose 3, 1 month after 13vPnC Dose 4 |