CIRN Pneumococcal Conjugate Vaccine 1 vs. 2 Dose Priming Study

Study Overview
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Brief Summary
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This study is assessing if a reduced dosing schedule (1+1) of the 13-valent pneumococcal conjugate vaccine (PCV13) is non-inferior to the currently used schedule used in most of Canada.The vaccine is currently usually given as 3 doses at 2, 4 and 12 months of age. This study aims to find out if it is possible to achieve the same protection using just 2 doses, at 2 and 12 months.

Official Title
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A Randomized Controlled Trial to Compare a 1-dose vs. 2-dose Priming Schedule of 13-valent Pneumococcal Conjugate Vaccine in Canadian Infants; a Canadian Immunization Research Network (CIRN) Study

Conditions
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Invasive Pneumococcal Disease, Protection Against, Streptococcus Pneumoniae Infection

Intervention / Treatment
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* Biological: PCV13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infant born at ≥37 weeks' gestation Age 2 months (+ up to 14 days) at time of first study visit Parent/guardian or legally authorized representative has given informed consent for their child's participation. Exclusion Criteria: Already received any routine 2-month immunizations Previous laboratory confirmed pneumococcal disease Previous receipt of any pneumococcal vaccine Confirmed or suspected immunodeficiency, including but not limited to: Congenital or acquired asplenia, or splenic dysfunction B-cell (humoral), T-cell mediated, complement, or phagocytic function deficiency HIV infection Hematopoietic stem cell transplant (recipient) Malignant neoplasms, including leukemia and lymphoma Nephrotic syndrome Solid organ or islet transplant (candidate or recipient) A family history of congenital or hereditary immunodeficiency Use of systemic immunosuppressive medication, including long-term corticosteroids, chemotherapy, radiation therapy, post-organ transplant therapy, intravenous immunoglobulin and/or specific monoclonal antibody therapy Bleeding disorder or thrombocytopenia, that contraindicates intramuscular (IM) injection and/or blood collection or taking any anti-platelet or anti-coagulant medications Any contraindication to vaccination as per the NACI Canadian Immunization Guide (https://www.canada.ca/en/public-health/services/canadian-immunization-guide.html, accessed 16 September 2017). Note these factors will be considered an exclusion if known at the time of trial enrollment, but specific screening and/or testing for these conditions will not be part of the trial): Anaphylaxis to any vaccine or vaccine component being given during the trial, including PCV13 and other routine vaccines Any other previous adverse event which in the opinion of the Investigator is a contraindication to any vaccine being given during the trial Congenital malformation of the gastrointestinal tract or previous intussusception (rotavirus vaccine contraindicated) Active, untreated tuberculosis (MMR, varicella, MMRV contraindicated) Additional factors resulting in increased risk of pneumococcal disease as per the National Advisory Committee on Immunization (NACI) Canadian Immunization Guide (16 September 2017) Chronic cerebrospinal fluid (CSF) leak Chronic neurologic condition that may impair clearance of oral secretions Cochlear implants, including children who are due to receive implants Chronic heart disease Diabetes mellitus Chronic kidney disease Chronic liver disease, including hepatic cirrhosis due to any cause Chronic lung disease Sickle cell disease or other hemoglobinopathy Mother received pneumococcal vaccine during pregnancy Mother using systemic immunosuppressive medication during pregnancy, including intravenous immunoglobulin and/or specific monoclonal antibody therapy Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. Temporary exclusion criteria: - If an infant has a temperature ≥ 38°C, then vaccination (and blood and fecal sampling if due to occur at the same visit) will be postponed until resolution of fever.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group 1: 3 doses of PCV13 (2, 4, 12 months), 2+1 Group 2: 2 doses of PCV13 (2, 12 months), 1+1
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: 3 doses of PCV13<br>PCV13, 0.5ml intramuscular at 2, 4 and 12 months of age | Biological: PCV13<br>* Vaccine against pneumococcal disease<br>* Other names: Prevnar 13;|
| Experimental: Group 2: 2 doses of PCV13<br>PCV13, 0.5ml intramuscular at 2 and 12 months of age | Biological: PCV13<br>* Vaccine against pneumococcal disease<br>* Other names: Prevnar 13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of PCV13 post-booster | Serotype-specific pneumococcal IgG concentration at 1 month post-booster dose | 13 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of PCV13 post-priming | Serotype-specific pneumococcal IgG concentration post-priming dose(s) | 5 months of age | 
| Proportion of protected infants post-booster | Proportion of infants achieving serotype-specific pneumococcal IgG concentration ≥0.35 µg/ml post-booster dose | 13 months of age | 
| Proportion of protected infants post-priming | Proportion of infants achieving serotype-specific pneumococcal IgG concentration ≥0.35 µg/ml post-priming dose(s) | 5 months of age | 
| Incidence of adverse events following PCV13 | Adverse events following immunization after doses of PCV13 | 2, 4 and 12 months of age |