Trial of Pneumococcal Vaccine Schedules in Ho Chi Minh City, Vietnam

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Menzies School of Health Research
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
GlaxoSmithKline
Murdoch Childrens Research Institute
Institut Pasteur
Information provided by (Responsible Party):
Menzies School of Health Research
ClinicalTrials.gov Identifier:
NCT01953510
First received: September 25, 2013
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

Pneumococcus is a group of bacteria that can cause pneumonia, meningitis and other diseases. These bacteria normally live in the nose of humans and are spread from person to person by touching or sneezing. There are vaccines available to protect against infection with these bacteria, and pneumococcus is currently the leading vaccine-preventable cause of death in young children. In countries where pneumococcal vaccine (PCV) has been introduced, there has been a big impact on the amount of disease caused by these bacteria. However, many countries, especially developing countries, are yet to introduce PCV as part of their routine immunizations. Currently a total of four doses of PCV is recommended, and the main barrier to vaccine introduction is cost. This study aims to identify a vaccination schedule to make PCV more effective and affordable for Vietnam and other developing countries.

This study has two distinct purposes: 1) to compare different dosage schedules of PCV and 2) to compare different PCV vaccines.

  1. Schedules of Synflorix (PCV10) involving a three, two or one dose PCV primary series and two booster options will be compared. Comparisons will be made firstly in terms of measures of immunity to the vaccine, and secondly in terms of the effect of vaccination on the carriage of bacteria in the nose.
  2. The responses to PCV10 and Prevenar-13 (PCV13) will be compared, in the schedule most likely to be considered for global use. Again, comparisons will be made in terms of measures of immunity and effect on carriage in the nose.

Infants aged two months will be randomly assigned to one of six study groups and will provide up to four blood samples for analysis of the measures of immunity and five nose swabs for analysis of carriage of bacteria. Infants will be followed up 8-9 times until the age of 18-21 months.

The results of this study will be used to facilitate decision making, at global and national levels, regarding introduction of PCV.


Condition Intervention Phase
Pneumococcal Vaccines
Biological: PCV10
Biological: PCV13
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of Different Infant Vaccination Schedules Incorporating Pneumococcal Vaccination

Resource links provided by NLM:


Further study details as provided by Menzies School of Health Research:

Primary Outcome Measures:
  • proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes [ Time Frame: 4 weeks post-primary series ] [ Designated as safety issue: No ]
    The immunogenicity of PCV will be measured by ELISA in terms of serotype-specific IgG antibody concentrations. Primary comparisons between arms will be made in terms of the proportion of children with antibody concentration ≥0.35µg/mL for the ten serotypes included in both PCVs. An overall conclusion for between arm comparisons will be based on the rejection of at least seven out of the ten individual serotype null hypotheses.


Secondary Outcome Measures:
  • geometric mean concentration (GMC) of pneumococcal serotype-specific IgG [ Time Frame: four weeks post-primary series ] [ Designated as safety issue: No ]
    measured by ELISA

  • proportion of children with pneumococcal serotype-specific opsonisation index (OI) ≥8 [ Time Frame: four weeks post-primary series ] [ Designated as safety issue: No ]
    OIs for selected pneumococcal serotypes will be measured by opsonophagocytic assay (OPA)

  • proportion of children with four-fold rise in pneumococcal serotype-specific IgG [ Time Frame: change from pre-booster to four weeks post-booster ] [ Designated as safety issue: No ]
    measured by ELISA

  • proportion of children with pneumococcal serotype-specific OI ≥8 [ Time Frame: four weeks post-booster ] [ Designated as safety issue: No ]
    measured by OPA

  • median number of pneumococcal polysaccharide (PS)-specific memory B cells [ Time Frame: four weeks post-booster ] [ Designated as safety issue: No ]
    The number of PS-specific memory B cells will be measured by ELISPOT assays.

  • median proportion of pneumococcal PS-specific memory B cells [ Time Frame: four weeks post-booster ] [ Designated as safety issue: No ]
    The proportion of PS-specific memory B cells will be measured in relation to the total number of memory B cells.

  • median number of pneumococcal PS-specific memory B cells [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]
    measured by ELISPOT

  • median proportion of pneumococcal PS-specific memory B cells [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]
    measured by ELISPOT

  • NP carriage rate of NTHi [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of vaccine-type (VT) Streptococcus pneumoniae (S. pneumoniae) [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of non-VT S. pneumoniae [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of H. influenzae [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
  • Density of NP carriage of S. pneumoniae [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
    measured by quantitative real-time PCR (qPCR)

  • Density of NP carriage of H. influenzae [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
    measured by qPCR

  • NP carriage rate of NTHi [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of VT S. pneumoniae [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of non-VT S. pneumoniae [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of H. influenzae [ Time Frame: 18 months of age ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • proportion of children with a measles IgG antibody titre >150mIU/mL [ Time Frame: four weeks post-booster ] [ Designated as safety issue: No ]
    measured by ELISA

  • proportion of children achieving protective antibody levels to the components of Infanrix-hexa [ Time Frame: four weeks post-primary series ] [ Designated as safety issue: No ]
    Protective antibody levels are defined as: >0.1 IU/mL diphtheria IgG, >0.15 IU/mL tetanus IgG, >0.15 µg/mL Hib PRP antigen IgG, and >10 mIU/mL hepatitis B surface antigen IgG.

  • proportion of children achieving the expected booster-response antibody levels to the components of Infanrix-hexa [ Time Frame: four weeks post-booster ] [ Designated as safety issue: No ]
    The expected booster-response antibody levels are : >1.0 IU/mL diphtheria IgG, >1.0 IU/mL tetanus IgG, >1.0 µg/mL Hib PRP antigen IgG, and >1000 IU/mL hepatitis B surface antigen IgG.

  • NP carriage rate of VT S. pneumoniae [ Time Frame: 2 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of non-VT S. pneumoniae [ Time Frame: 2 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of H. influenzae [ Time Frame: 2 months of age ] [ Designated as safety issue: No ]
  • NP carriage rate of NTHi [ Time Frame: 2 months of age ] [ Designated as safety issue: No ]

Estimated Enrollment: 1200
Study Start Date: September 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: 3+1 Synflorix
PCV10 administered at 2, 3, 4 and 9 months of age
Biological: PCV10
PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein
Other Names:
  • 10-valent pneumococcal conjugate vaccine
  • Synflorix
Experimental: B: 3+0 Synflorix
PCV10 administered at 2, 3 and 4 months of age
Biological: PCV10
PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein
Other Names:
  • 10-valent pneumococcal conjugate vaccine
  • Synflorix
Experimental: C: 2+1 Synflorix
PCV10 administered at 2, 4 and 9 months of age
Biological: PCV10
PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein
Other Names:
  • 10-valent pneumococcal conjugate vaccine
  • Synflorix
Experimental: D: 1+1 Synflorix
PCV10 administered at 2 and 6 months of age
Biological: PCV10
PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein
Other Names:
  • 10-valent pneumococcal conjugate vaccine
  • Synflorix
Experimental: E: 2+1 Prevenar
PCV13 administered at 2, 4 and 9 months of age
Biological: PCV13
PCV13 includes serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, individually linked to non-toxic diphtheria CRM197 carrier protein
Other Names:
  • 13-valent pneumococcal conjugate vaccine
  • Prevenar-13
  • Prevnar-13
No Intervention: F: control
No infant PCV vaccination. PCV10 administered at 18 and 20 months of age

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Days to 74 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged between 2 months and 2 months plus 2 weeks
  • No significant maternal or perinatal history
  • Born at or after 36 weeks gestation
  • Written and signed informed consent from parent/legal guardian
  • Lives within approximately 30 minutes of the commune health centre
  • Family anticipates living in the study area for the next 19 months

Exclusion Criteria:

  • Known allergy to any component of the vaccine;
  • Allergic reaction or anaphylactic reaction to any previous vaccine;
  • Known immunodeficiency disorder;
  • Known HIV-infected mother;
  • Known thrombocytopenia or coagulation disorder;
  • On immunosuppressive medication;
  • Administration or planned administration of any immunoglobulin or blood product since birth;
  • Severe birth defect requiring ongoing medical care;
  • Chronic or progressive disease;
  • Seizure disorder;
  • History of invasive pneumococcal, meningococcal or Haemophilus influenzae type b diseases, or tetanus, measles, pertussis or diphtheria infections;
  • Receipt of any 2 month vaccines through the EPI program;
  • Family plans on giving the infant the Quinvaxem (DTP-Hib-HBV) or oral polio vaccines
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953510

Contacts
Contact: Beth Temple, MSc, BA +61407029329 beth.temple@menzies.edu.au

Locations
Vietnam
Pasteur Institute of Ho Chi Minh City Recruiting
Ho Chi Minh City, Vietnam
Contact: Kathryn Bright, BSc    +841264605993    kathryn.bright@menzies.edu.au   
Principal Investigator: Tran Ngoc Huu, MD         
Sponsors and Collaborators
Menzies School of Health Research
National Health and Medical Research Council, Australia
GlaxoSmithKline
Murdoch Childrens Research Institute
Institut Pasteur
Investigators
Principal Investigator: Edward K Mulholland, MBBS, FRACP Menzies School of Health Research
  More Information

No publications provided

Responsible Party: Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT01953510     History of Changes
Other Study ID Numbers: 09/19, 566792, 10PN-PD-DIT-079
Study First Received: September 25, 2013
Last Updated: March 7, 2014
Health Authority: Australia: Human Research Ethics Committee
Vietnam: Ministry of Health
Vietnam: Ho Chi Minh City Health Service

Keywords provided by Menzies School of Health Research:
Pneumococcal vaccines
10-valent pneumococcal vaccine
13-valent pneumococcal vaccine
Immunization Schedule
Public Health

ClinicalTrials.gov processed this record on October 23, 2014