CIRN Pneumococcal Conjugate Vaccine 1 vs. 2 Dose Priming Study

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

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.

Study Overview

• Status: Completed
• Conditions: Streptococcus Pneumoniae Infection; Invasive Pneumococcal Disease, Protection Against
• Intervention / Treatment: Biological: PCV13

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • Vaccine Evaluation Center (University of BC at Children's Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Storage of fecal samples for analysis of the influence of the infant microbiome on vaccine responses	Collection of fecal samples at time of vaccination	2, 4, 6 and 12 months of age
Immunogenicity of PCV13 after maternal pertussis immunization	Comparison of primary and secondary endpoints in infants born to mothers who received pertussis immunization in pregnancy vs. those that did not	5 and 13 months
Rate of nasopharyngeal colonization after vaccination with S. pneumoniae	Comparison of nasopharyngeal colonization rate with S. pneumoniae in Group 1 vs. Group 2	13 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR); University of Calgary; Alberta Children's Hospital; IWK Health Centre; Université de Montréal; Canadian Immunization Research Network
• Investigators: Principal Investigator: Manish Sadarangani, MD, UBC

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2018
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 27, 2017

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: H17-02645; CIRN23/CT16 (Other Identifier: UBC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes