Clinical trial NCT03384589: CIRN Pneumococcal Conjugate Vaccine 1 vs. 2 Dose Priming Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Invasive Pneumococcal Disease, Protection Against
Streptococcus Pneumoniae Infection
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Immunization Research Network
name: Alberta Children's Hospital
name: Université de Montréal
name: IWK Health Centre
name: University of Calgary
name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-12-27
Enrollment: 248
Sex: ALL
Minimum age (years): 2
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: PREVENTION

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.


Eligibility 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 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.

Primary outcomes:
measure: Immunogenicity of PCV13 post-booster
timeFrame: 13 months of age
Secondary outcomes:
measure: Immunogenicity of PCV13 post-priming
timeFrame: 5 months of age
measure: Proportion of protected infants post-booster
timeFrame: 13 months of age
measure: Proportion of protected infants post-priming
timeFrame: 5 months of age
measure: Incidence of adverse events following PCV13
timeFrame: 2, 4 and 12 months of age
Other outcomes:
measure: Storage of fecal samples for analysis of the influence of the infant microbiome on vaccine responses
timeFrame: 2, 4, 6 and 12 months of age
measure: Immunogenicity of PCV13 after maternal pertussis immunization
timeFrame: 5 and 13 months
measure: Rate of nasopharyngeal colonization after vaccination with S. pneumoniae
timeFrame: 13 months
Locations:
city: Vancouver
country: Canada
facility: Vaccine Evaluation Center (University of BC at Children's Hospital)
state: British Columbia
Study officials:
affiliation: UBC
name: Manish Sadarangani, MD
role: PRINCIPAL_INVESTIGATOR
References: