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

NCT01953510 | Completed Phase 2

• 3 other identifiers: 09/1956679210PN-PD-DIT-079
• Study Type: interventional
• Target: 1,400
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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.

Conditions

Pneumococcal Vaccines

Keywords

Pneumococcal vaccines; 10-valent pneumococcal vaccine; 13-valent pneumococcal vaccine; Immunization Schedule; Public Health

Outcome Measures

Primary Outcomes (1)

• proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes

  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.

  4 weeks post-primary series

Secondary Outcomes (19)

• geometric mean concentration (GMC) of pneumococcal serotype-specific IgG

  four weeks post-primary series

• proportion of children with pneumococcal serotype-specific opsonisation index (OI) ≥8

  four weeks post-primary series

• proportion of children with four-fold rise in pneumococcal serotype-specific IgG

  change from pre-booster to four weeks post-booster

• proportion of children with pneumococcal serotype-specific OI ≥8

  four weeks post-booster

• median number of pneumococcal polysaccharide (PS)-specific memory B cells

  four weeks post-booster

Other Outcomes (7)

• proportion of children with a measles IgG antibody titre >150mIU/mL

  four weeks post-booster

• proportion of children achieving protective antibody levels to the components of Infanrix-hexa

  four weeks post-primary series

• proportion of children achieving the expected booster-response antibody levels to the components of Infanrix-hexa

  four weeks post-booster

Study Arms (7)

A: 3+1 PCV10

ACTIVE COMPARATOR

PCV10 administered at 2, 3, 4 and 9 months of age

Biological: PCV10

B: 3+0 PCV10

EXPERIMENTAL

PCV10 administered at 2, 3 and 4 months of age

Biological: PCV10

C: 2+1 PCV10

EXPERIMENTAL

PCV10 administered at 2, 4 and 9 months of age

Biological: PCV10

D: 1+1 PCV10

EXPERIMENTAL

PCV10 administered at 2 and 6 months of age

Biological: PCV10

E: 2+1 PCV13

EXPERIMENTAL

PCV13 administered at 2, 4 and 9 months of age

Biological: PCV13

F: control

NO INTERVENTION

No infant PCV vaccination. PCV10 administered at 18 and 24 months of age

G: control

NO INTERVENTION

Recruited at 18 months of age (non-randomised). PCV10 administered at 24 months of age

Interventions

PCV10 BIOLOGICAL

PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein

Also known as: 10-valent pneumococcal conjugate vaccine, Synflorix

A: 3+1 PCV10; B: 3+0 PCV10; C: 2+1 PCV10; D: 1+1 PCV10

PCV13 BIOLOGICAL

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

Also known as: 13-valent pneumococcal conjugate vaccine, Prevenar-13, Prevnar-13

E: 2+1 PCV13

Eligibility Criteria

• Age: 60 Days - 74 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Aged between 2 months and 2 months plus 2 weeks (Arms A-F) or aged between 18 months and 18 months plus 2 weeks (Arm G)
• 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 22 months (Arms A-F) or 6 months (Arm G)
• Has received three doses of either Infanrix-hexa or Quinvaxem in infancy (Arm G)

You may not qualify if:

• 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 (Arms A-F) or receipt of PCV (Arm G)
• Family plans on giving the infant Quinvaxem or oral polio vaccine (Arms A-F)

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Institut Pasteur: collaborator
• Menzies School of Health Research: collaborator
• National Health and Medical Research Council, Australia: collaborator
• Bill and Melinda Gates Foundation: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Pasteur Institute of Ho Chi Minh City

Ho Chi Minh City, Vietnam

Location

Related Publications (6)

• Toh ZQ, Ma YY, Temple B, Anderson J, Far HH, Phan TV, Dai VTT, Huu TN, Toan NT, Bright K, Nation ML, Ortika BD, Nguyen C, Smith-Vaughan H, Satzke C, Mulholland K, Licciardi PV. Relationship between IL-17_A and pneumococcal carriage in children aged under two years: data from a randomised controlled trial in Vietnam. Cytokine. 2026 Feb;198:157094. doi: 10.1016/j.cyto.2025.157094. Epub 2025 Dec 23.

  PMID: 41442837 DERIVED

• Smith-Vaughan H, Temple B, Trang Dai VT, Hoan PT, Loc Thuy HN, Phan TV, Bright K, Toan NT, Uyen DY, Nguyen CD, Beissbarth J, Ortika BD, Nation ML, Dunne EM, Hinds J, Lai J, Satzke C, Huu TN, Mulholland K. Effect of different schedules of ten-valent pneumococcal conjugate vaccine on pneumococcal carriage in Vietnamese infants: results from a randomised controlled trial. Lancet Reg Health West Pac. 2022 Dec 3;32:100651. doi: 10.1016/j.lanwpc.2022.100651. eCollection 2023 Mar.

  PMID: 36785850 DERIVED

• Licciardi PV, Temple B, Dai VTT, Toan NT, Uyen D, Nguyen CD, Phan TV, Bright K, Marimla RA, Balloch A, Huu TN, Mulholland K. Immunogenicity of alternative ten-valent pneumococcal conjugate vaccine schedules in infants in Ho Chi Minh City, Vietnam: results from a single-blind, parallel-group, open-label, randomised, controlled trial. Lancet Infect Dis. 2021 Oct;21(10):1415-1428. doi: 10.1016/S1473-3099(20)30775-1. Epub 2021 Jun 23.

  PMID: 34171233 DERIVED

• Temple B, Nation ML, Dai VTT, Beissbarth J, Bright K, Dunne EM, Hinds J, Hoan PT, Lai J, Nguyen CD, Ortika BD, Phan TV, Thuy HNL, Toan NT, Uyen DY, Satzke C, Smith-Vaughan H, Huu TN, Mulholland K. Effect of a 2+1 schedule of ten-valent versus 13-valent pneumococcal conjugate vaccine on pneumococcal carriage: Results from a randomised controlled trial in Vietnam. Vaccine. 2021 Apr 15;39(16):2303-2310. doi: 10.1016/j.vaccine.2021.02.043. Epub 2021 Mar 19.

  PMID: 33745731 DERIVED

• Temple B, Toan NT, Dai VTT, Bright K, Licciardi PV, Marimla RA, Nguyen CD, Uyen DY, Balloch A, Huu TN, Mulholland EK. Immunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial. Lancet Infect Dis. 2019 May;19(5):497-509. doi: 10.1016/S1473-3099(18)30734-5. Epub 2019 Apr 8.

  PMID: 30975525 DERIVED

• Temple B, Toan NT, Uyen DY, Balloch A, Bright K, Cheung YB, Licciardi P, Nguyen CD, Phuong NTM, Satzke C, Smith-Vaughan H, Vu TQH, Huu TN, Mulholland EK. Evaluation of different infant vaccination schedules incorporating pneumococcal vaccination (The Vietnam Pneumococcal Project): protocol of a randomised controlled trial. BMJ Open. 2018 Jun 8;8(6):e019795. doi: 10.1136/bmjopen-2017-019795.

  PMID: 29884695 DERIVED

MeSH Terms

Interventions

10-valent pneumococcal conjugate vaccine; PHiD-CV vaccine; 13-valent pneumococcal vaccine

Study Officials

• Edward K Mulholland, MBBS, FRACP

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2013
• First Posted: October 1, 2013
• Study Start: September 30, 2013
• Primary Completion: January 27, 2016
• Study Completion: November 8, 2021
• Last Updated: September 14, 2022

Record last verified: 2022-09

Locations

VN (1)