CIRN Pnuemococcal Conjugate Vaccine 1 vs. 2 Dose Priming Study

• ClinicalTrials.gov Identifier: NCT03384589
• Recruitment Status: Active, not recruiting
• First Posted: December 27, 2017
• Last Update Posted: February 7, 2020
• Sponsor: University of British Columbia
• Collaborators: Canadian Immunization Research Network; Alberta Children's Hospital; Université de Montréal; IWK Health Centre; University of Calgary; Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Manish Sadarangani, University of British Columbia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Invasive Pneumococcal Disease, Protection Against; Streptococcus Pneumoniae Infection	Biological: PCV13	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 248 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: August 23, 2018
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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 Name: 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 Name: Prevnar 13

Outcome Measures

Primary Outcome Measures :

1. Immunogenicity of PCV13 post-booster [ Time Frame: 13 months of age ]
   Serotype-specific pneumococcal IgG concentration at 1 month post-booster dose

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 2 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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 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 hemoglobinoptahy
• 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.

Contacts and Locations

Locations

Canada, British Columbia

Vaccine Evaluation Center (University of BC at Children's Hospital)

Vancouver, British Columbia, Canada, V5Z 4H4

Sponsors and Collaborators

University of British Columbia

Canadian Immunization Research Network

Alberta Children's Hospital

Université de Montréal

IWK Health Centre

University of Calgary

Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Manish Sadarangani, MD; UBC

More Information

• Responsible Party: Manish Sadarangani, Principle Investigator, University of British Columbia
• ClinicalTrials.gov Identifier: NCT03384589
• Other Study ID Numbers: H17-02645; CIRN23/CT16 ( Other Identifier: UBC )
• First Posted: December 27, 2017
• Last Update Posted: February 7, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Pneumococcal Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs