Pneumococcal VaccinesPhase 2/3NCT01953510
Trial of Pneumococcal Vaccine Schedules in Ho Chi Minh City, Vietnam
A Phase 2/3 study testing PCV10 and PCV13 in people with Pneumococcal Vaccines, run by Murdoch Childrens Research Institute at 1 site in Vietnam.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 74 daysHealthy volunteers can take part
- Conditions the study is for
- Pneumococcal Vaccines
- What is being tested?
- PCV10 and PCV13
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,400 participants
- Where
- 1 siteVietnam
- Study dates
- 30 Sep 2013to 8 Nov 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 74 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Show all 13Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Different Infant Vaccination Schedules Incorporating Pneumococcal Vaccination
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.
Read more
- 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.
- 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 24 months. An additional control group will be recruited at 18 months of age and also followed up until 24 months of age.
The results of this study will be used to facilitate decision making, at global and national levels, regarding introduction of PCV.
Read the detailed description
Introduction
The overall purpose of this study is to investigate simplified childhood vaccination schedules that are more appropriate for developing country use. This study is specifically designed to address two independent questions within a single study:
- What is the optimal schedule for provision of EPI vaccines with the incorporation of PCV10? Schedules involving a three, two or one dose PCV10 primary series will be evaluated, timed around options for simplification of the Expanded Programme of Immunization (EPI) schedule for developing countries. A simplified schedule with the pneumococcal booster dose brought forward closer to the peak incidence of disease is likely both to increase compliance and vaccine effectiveness. A booster at nine months of age coincides with the usual time for administration of measles vaccine, whereas a booster at six months of age would provide earlier protection and may enable a further abbreviated 1+1 pneumococcal vaccination schedule.
- How do the responses to PCV vaccination with PCV10 or PCV13 compare? PCV10 and PCV13 are the two PCVs available through the Advanced Market Commitment (AMC) mechanism, a mechanism that provides funds for vaccine introduction into developing countries. However, there have been no studies to date directly comparing these two vaccines. Directly comparing these two vaccines will provide useful information to countries considering introduction of PCV. There are important differences between these vaccines. PCV10 includes ten pneumococcal serotypes and PCV13 includes thirteen. PCV10 uses a non-typeable Haemophilus influenzae (NTHi) Protein D carrier, which may confer protection against H. influenzae, and PCV13 uses a CRM197 carrier. It is of interest to know whether these vaccines differ either in their immunogenicity or their impact on nasopharyngeal (NP) carriage.
Design
Infants will be randomized to one of six study arms (A-F). All infant participants receive four doses of Infanrix-hexa (DTaP-Hib-HBV-IPV) and at least two doses of PCV. The PCV schedules to be evaluated are: a 3+1 PCV10 schedule at 2, 3, 4 and 9 months of age (Arm A); a 3+0 PCV10 schedule at 2, 3 and 4 months of age (Arm B); a 2+1 PCV10 schedule at 2, 4 and 9 months of age (Arm C); a 1+1 PCV10 schedule at 2 and 6 months of age (Arm D); a 2+1 PCV13 schedule at 2, 4 and 9 months of age (Arm E). Arm F, the control group, receives two doses of PCV10 at 18 and 24 months of age. An additional control group (Arm G) will be recruited at 18 months of age and will receive Infanrix-hexa at 18 months of age and a single dose of PCV10 at 24 months of age. Reactogenicity will be assessed following all vaccination visits through the use of diary cards.
Participants from arms A-E will provide six NP swabs for analysis of the NP carriage outcomes, at 2, 6, 9, 12, 18 and 24 months of age; and will provide four blood samples over the course of the trial for analysis of vaccine responses. Blood 1 will be taken four weeks post-primary series; Blood 2 will be taken pre-booster (arms A, C, D and E) or at 9 months of age (subset of arm B); and Blood 3 will be taken four weeks post-booster (arms A, C, D and E) or at 10 months of age (arm B). An additional blood sample will be taken at: 18 months of age for a subset of arms A, B, C, D and E; 2 months of age for a subset of arm A; 6 months of age for a subset of arms B and C; 9 months of age for a subset of arm D; or 3 months of age for a subset of arm E. Participants from the control arms will provide NP swabs at 2, 6, 9, 12, 18 and 24 months of age (arm F) or at 18 and 24 months of age (arm G), and will provide blood samples at 18 (Blood 4), 19 (Blood X) and 24 (Blood Y) months of age.
Objectives
- What is the optimal schedule for provision of EPI vaccines with the incorporation of PCV10? The primary objective is to compare a 2+1 schedule at 2, 4 and 9 months of age with a 3+1 schedule at 2, 3, 4 and 9 months of age, with a primary outcome of the immunogenicity of PCV10, four weeks post-primary series (Arm C vs. Arm A+B). Secondary objectives are to investigate an experimental 1+1 schedule at 2 and 6 months of age (Arm D vs. Arm A+B and Arm D vs. Arm C), and to assess the impact of a booster dose on carriage (Arm A vs. Arm F and Arm A vs. Arm B).
- How do the responses to PCV vaccination with PCV10 or PCV13 compare? The primary objective is to compare a PCV13 schedule at 2, 4 and 9 months of age with a PCV10 schedule at 2, 3, 4 and 9 months of age, with a primary outcome of the immunogenicity of PCV, four weeks post-primary series (Arm E vs. Arm A+B). Secondary objectives are to compare a PCV13 schedule at 2, 4 and 9 months of age with a PCV10 schedule at 2, 4 and 9 months of age (Arm E vs. Arm C), and to compare the responses to a single dose of PCV13 or PCV10 (Arm E vs. Arm D).
Other objectives are: to examine the decline in pneumococcal antibody levels over time (Arm B); to describe the serotype profile of transferred maternal pneumococcal antibodies (Arm A); and to describe the early rates of carriage (Arms A-F); to evaluate a single dose of PCV10 at 18 months of age (Arm F); and to evaluate the immunogenicity of Infanrix-hexa at 18 months of age in children who have received three doses of Infanrix-hexa or three doses of Quinvaxem (DTwP-Hib-HBV) in infancy.
Sample Size
The proposed infant sample size is 1200 with an allocation ratio of 3:3:5:4:5:4, resulting in arm sizes of: A=150, B=150, C=250, D=200, E=250, F=200. Sample size calculations were based on the primary outcomes for each of the two study questions: the post-primary series immunogenicity comparing 1) a two dose (Arm C) and three dose (Arm A+B) PCV10 primary series and 2) a two dose PCV13 (Arm E) and three dose PCV10 (Arm A+B) primary series. A non-inferiority margin of 10% difference in absolute risk (Arm A+B minus Arm C or Arm E), as used by regulatory authorities, is deemed clinically significant. The Farrington-Manning (1990) method was used for the sample size/power estimation, assuming one-sided 5% type I error. If the alternative hypotheses of non-inferiority are accepted for at least 7 out of 10 serotypes, overall non-inferiority will be declared. The power for testing individual serotype hypotheses was calculated using PASS Software 2002. The power for rejecting the overall null hypothesis was estimated by simulation, using a tailor-made simulation program written for implementation in Stata with 10,000 replications. A sample size of 1200 results in >99% power for rejecting the overall null hypothesis for each of the two study questions, allowing for 5% loss to follow-up at four weeks post-primary series. An additional 200 participants aged 18 months (Arm G) will be recruited at the same time as participants from Arms A-F reach 18 months of age, bringing the total sample size of the trial to 1400 participants.
- Conditions
- Pneumococcal Vaccines
- Being tested
- PCV10, PCV13
- Keywords
- Pneumococcal vaccines, 10-valent pneumococcal vaccine, 13-valent pneumococcal vaccine, Immunization Schedule, Public Health
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCV10Biological
Also called 10-valent pneumococcal conjugate vaccine, Synflorix
PCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein
PCV13Biological
Also called 13-valent pneumococcal conjugate vaccine, Prevenar-13, Prevnar-13
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
| Study group | Role | What they receive |
|---|---|---|
| A: 3+1 PCV10 | Active comparator | PCV10 administered at 2, 3, 4 and 9 months of age Receives: Biological: PCV10 |
| B: 3+0 PCV10 | Experimental | PCV10 administered at 2, 3 and 4 months of age Receives: Biological: PCV10 |
| C: 2+1 PCV10 | Experimental | PCV10 administered at 2, 4 and 9 months of age Receives: Biological: PCV10 |
| D: 1+1 PCV10 | Experimental | PCV10 administered at 2 and 6 months of age Receives: Biological: PCV10 |
| E: 2+1 PCV13 | Experimental | PCV13 administered at 2, 4 and 9 months of age Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks post-primary series
Secondary outcomes (19)
geometric mean concentration (GMC) of pneumococcal serotype-specific IgG
measured by ELISA
Measured: four weeks post-primary series
proportion of children with pneumococcal serotype-specific opsonisation index (OI) ≥8
OIs for selected pneumococcal serotypes will be measured by opsonophagocytic assay (OPA)
Measured: four weeks post-primary series
proportion of children with four-fold rise in pneumococcal serotype-specific IgG
measured by ELISA
Measured: change from pre-booster to four weeks post-booster
proportion of children with pneumococcal serotype-specific OI ≥8
measured by OPA
Measured: four weeks post-booster
median number of pneumococcal polysaccharide (PS)-specific memory B cells
The number of PS-specific memory B cells will be measured by ELISPOT assays.
Measured: four weeks post-booster
median proportion of pneumococcal PS-specific memory B cells
The proportion of PS-specific memory B cells will be measured in relation to the total number of memory B cells.
Measured: four weeks post-booster
median number of pneumococcal PS-specific memory B cells
measured by ELISPOT
Measured: 18 months of age
median proportion of pneumococcal PS-specific memory B cells
measured by ELISPOT
Measured: 18 months of age
NP carriage rate of NTHi
Measured: 12 months of age
NP carriage rate of vaccine-type (VT) Streptococcus pneumoniae (S. pneumoniae)
Measured: 12 months of age
NP carriage rate of non-VT S. pneumoniae
Measured: 12 months of age
NP carriage rate of H. influenzae
Measured: 12 months of age
Density of NP carriage of S. pneumoniae
measured by quantitative real-time PCR (qPCR)
Measured: 12 months of age
Density of NP carriage of H. influenzae
measured by qPCR
Measured: 12 months of age
NP carriage rate of NTHi
Measured: 18 months of age
NP carriage rate of VT S. pneumoniae
Measured: 18 months of age
NP carriage rate of non-VT S. pneumoniae
Measured: 18 months of age
NP carriage rate of H. influenzae
Measured: 18 months of age
NP carriage rate of VT S. pneumoniae
assessed primarily by qPCR and microarray
Measured: 24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2013 (estimated)
- Study start30 Sep 2013
- Primary completion27 Jan 2016
- Study completion8 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Pneumococcal VaccinesStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Institut Pasteur, Menzies School of Health Research, National Health and Medical Research Council, Australia, Bill and Melinda Gates Foundation, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Edward K Mulholland, MBBS, FRACP, Principal investigator, Murdoch Childrens Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01953510
- Sponsor's protocol ID
- 09/19
- Other IDs
- 566792, 10PN-PD-DIT-079
- Status last verified
- Sep 2022
- First submitted
- 25 Sep 2013
- Last updated
- 14 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 41442837Smith-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.
PubMed 36785850Licciardi 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.
PubMed 34171233Temple 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.
PubMed 33745731Temple 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.
PubMed 30975525Temple 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.
PubMed 29884695
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Different Infant Vaccination Schedules Incorporating Pneumococcal Vaccination
- ClinicalTrials.gov ID
- NCT01953510
- Acronym / sponsor ID
- 09/19
- Conditions
- Pneumococcal Vaccines
- Keywords
- Pneumococcal vaccines, 10-valent pneumococcal vaccine, 13-valent pneumococcal vaccine, Immunization Schedule, Public Health
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,400 participants (actual)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Collaborators
- Institut Pasteur, Menzies School of Health Research, National Health and Medical Research Council, Australia, Bill and Melinda Gates Foundation, GlaxoSmithKline
- Study start
- 30 Sep 2013 (actual)
- Primary completion
- 27 Jan 2016 (actual)
- Study completion
- 8 Nov 2021 (actual)
- First posted
- 1 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
- 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 24 months. An additional control group will be recruited at 18 months of age and also followed up until 24 months of age.
The results of this study will be used to facilitate decision making, at global and national levels, regarding introduction of PCV.
Detailed description
Introduction
The overall purpose of this study is to investigate simplified childhood vaccination schedules that are more appropriate for developing country use. This study is specifically designed to address two independent questions within a single study:
- What is the optimal schedule for provision of EPI vaccines with the incorporation of PCV10? Schedules involving a three, two or one dose PCV10 primary series will be evaluated, timed around options for simplification of the Expanded Programme of Immunization (EPI) schedule for developing countries. A simplified schedule with the pneumococcal booster dose brought forward closer to the peak incidence of disease is likely both to increase compliance and vaccine effectiveness. A booster at nine months of age coincides with the usual time for administration of measles vaccine, whereas a booster at six months of age would provide earlier protection and may enable a further abbreviated 1+1 pneumococcal vaccination schedule.
- How do the responses to PCV vaccination with PCV10 or PCV13 compare? PCV10 and PCV13 are the two PCVs available through the Advanced Market Commitment (AMC) mechanism, a mechanism that provides funds for vaccine introduction into developing countries. However, there have been no studies to date directly comparing these two vaccines. Directly comparing these two vaccines will provide useful information to countries considering introduction of PCV. There are important differences between these vaccines. PCV10 includes ten pneumococcal serotypes and PCV13 includes thirteen. PCV10 uses a non-typeable Haemophilus influenzae (NTHi) Protein D carrier, which may confer protection against H. influenzae, and PCV13 uses a CRM197 carrier. It is of interest to know whether these vaccines differ either in their immunogenicity or their impact on nasopharyngeal (NP) carriage.
Design
Infants will be randomized to one of six study arms (A-F). All infant participants receive four doses of Infanrix-hexa (DTaP-Hib-HBV-IPV) and at least two doses of PCV. The PCV schedules to be evaluated are: a 3+1 PCV10 schedule at 2, 3, 4 and 9 months of age (Arm A); a 3+0 PCV10 schedule at 2, 3 and 4 months of age (Arm B); a 2+1 PCV10 schedule at 2, 4 and 9 months of age (Arm C); a 1+1 PCV10 schedule at 2 and 6 months of age (Arm D); a 2+1 PCV13 schedule at 2, 4 and 9 months of age (Arm E). Arm F, the control group, receives two doses of PCV10 at 18 and 24 months of age. An additional control group (Arm G) will be recruited at 18 months of age and will receive Infanrix-hexa at 18 months of age and a single dose of PCV10 at 24 months of age. Reactogenicity will be assessed following all vaccination visits through the use of diary cards.
Participants from arms A-E will provide six NP swabs for analysis of the NP carriage outcomes, at 2, 6, 9, 12, 18 and 24 months of age; and will provide four blood samples over the course of the trial for analysis of vaccine responses. Blood 1 will be taken four weeks post-primary series; Blood 2 will be taken pre-booster (arms A, C, D and E) or at 9 months of age (subset of arm B); and Blood 3 will be taken four weeks post-booster (arms A, C, D and E) or at 10 months of age (arm B). An additional blood sample will be taken at: 18 months of age for a subset of arms A, B, C, D and E; 2 months of age for a subset of arm A; 6 months of age for a subset of arms B and C; 9 months of age for a subset of arm D; or 3 months of age for a subset of arm E. Participants from the control arms will provide NP swabs at 2, 6, 9, 12, 18 and 24 months of age (arm F) or at 18 and 24 months of age (arm G), and will provide blood samples at 18 (Blood 4), 19 (Blood X) and 24 (Blood Y) months of age.
Objectives
- What is the optimal schedule for provision of EPI vaccines with the incorporation of PCV10? The primary objective is to compare a 2+1 schedule at 2, 4 and 9 months of age with a 3+1 schedule at 2, 3, 4 and 9 months of age, with a primary outcome of the immunogenicity of PCV10, four weeks post-primary series (Arm C vs. Arm A+B). Secondary objectives are to investigate an experimental 1+1 schedule at 2 and 6 months of age (Arm D vs. Arm A+B and Arm D vs. Arm C), and to assess the impact of a booster dose on carriage (Arm A vs. Arm F and Arm A vs. Arm B).
- How do the responses to PCV vaccination with PCV10 or PCV13 compare? The primary objective is to compare a PCV13 schedule at 2, 4 and 9 months of age with a PCV10 schedule at 2, 3, 4 and 9 months of age, with a primary outcome of the immunogenicity of PCV, four weeks post-primary series (Arm E vs. Arm A+B). Secondary objectives are to compare a PCV13 schedule at 2, 4 and 9 months of age with a PCV10 schedule at 2, 4 and 9 months of age (Arm E vs. Arm C), and to compare the responses to a single dose of PCV13 or PCV10 (Arm E vs. Arm D).
Other objectives are: to examine the decline in pneumococcal antibody levels over time (Arm B); to describe the serotype profile of transferred maternal pneumococcal antibodies (Arm A); and to describe the early rates of carriage (Arms A-F); to evaluate a single dose of PCV10 at 18 months of age (Arm F); and to evaluate the immunogenicity of Infanrix-hexa at 18 months of age in children who have received three doses of Infanrix-hexa or three doses of Quinvaxem (DTwP-Hib-HBV) in infancy.
Sample Size
The proposed infant sample size is 1200 with an allocation ratio of 3:3:5:4:5:4, resulting in arm sizes of: A=150, B=150, C=250, D=200, E=250, F=200. Sample size calculations were based on the primary outcomes for each of the two study questions: the post-primary series immunogenicity comparing 1) a two dose (Arm C) and three dose (Arm A+B) PCV10 primary series and 2) a two dose PCV13 (Arm E) and three dose PCV10 (Arm A+B) primary series. A non-inferiority margin of 10% difference in absolute risk (Arm A+B minus Arm C or Arm E), as used by regulatory authorities, is deemed clinically significant. The Farrington-Manning (1990) method was used for the sample size/power estimation, assuming one-sided 5% type I error. If the alternative hypotheses of non-inferiority are accepted for at least 7 out of 10 serotypes, overall non-inferiority will be declared. The power for testing individual serotype hypotheses was calculated using PASS Software 2002. The power for rejecting the overall null hypothesis was estimated by simulation, using a tailor-made simulation program written for implementation in Stata with 10,000 replications. A sample size of 1200 results in >99% power for rejecting the overall null hypothesis for each of the two study questions, allowing for 5% loss to follow-up at four weeks post-primary series. An additional 200 participants aged 18 months (Arm G) will be recruited at the same time as participants from Arms A-F reach 18 months of age, bringing the total sample size of the trial to 1400 participants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| A: 3+1 PCV10 | Active comparator | Biological: PCV10PCV10 administered at 2, 3, 4 and 9 months of age |
| B: 3+0 PCV10 | Experimental | Biological: PCV10PCV10 administered at 2, 3 and 4 months of age |
| C: 2+1 PCV10 | Experimental | Biological: PCV10PCV10 administered at 2, 4 and 9 months of age |
| D: 1+1 PCV10 | Experimental | Biological: PCV10PCV10 administered at 2 and 6 months of age |
| E: 2+1 PCV13 | Experimental | Biological: PCV13PCV13 administered at 2, 4 and 9 months of age |
| 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 |
Who may qualify
- Ages
- 60 to 74 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCV10Also: 10-valent pneumococcal conjugate vaccine, SynflorixPCV10 includes serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D is the main carrier protein | Biological | A: 3+1 PCV10, B: 3+0 PCV10, C: 2+1 PCV10, D: 1+1 PCV10 |
| PCV13Also: 13-valent pneumococcal conjugate vaccine, Prevenar-13, Prevnar-13PCV13 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 | Biological | E: 2+1 PCV13 |
Primary outcome
proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes
Time frame: 4 weeks post-primary series
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.
19 secondary outcomes
geometric mean concentration (GMC) of pneumococcal serotype-specific IgG
Time frame: four weeks post-primary series
proportion of children with pneumococcal serotype-specific opsonisation index (OI) ≥8
Time frame: four weeks post-primary series
proportion of children with four-fold rise in pneumococcal serotype-specific IgG
Time frame: change from pre-booster to four weeks post-booster
proportion of children with pneumococcal serotype-specific OI ≥8
Time frame: four weeks post-booster
median number of pneumococcal polysaccharide (PS)-specific memory B cells
Time frame: four weeks post-booster
median proportion of pneumococcal PS-specific memory B cells
Time frame: four weeks post-booster
median number of pneumococcal PS-specific memory B cells
Time frame: 18 months of age
median proportion of pneumococcal PS-specific memory B cells
Time frame: 18 months of age
NP carriage rate of NTHi
Time frame: 12 months of age
NP carriage rate of vaccine-type (VT) Streptococcus pneumoniae (S. pneumoniae)
Time frame: 12 months of age
NP carriage rate of non-VT S. pneumoniae
Time frame: 12 months of age
NP carriage rate of H. influenzae
Time frame: 12 months of age
Density of NP carriage of S. pneumoniae
Time frame: 12 months of age
Density of NP carriage of H. influenzae
Time frame: 12 months of age
NP carriage rate of NTHi
Time frame: 18 months of age
NP carriage rate of VT S. pneumoniae
Time frame: 18 months of age
NP carriage rate of non-VT S. pneumoniae
Time frame: 18 months of age
NP carriage rate of H. influenzae
Time frame: 18 months of age
NP carriage rate of VT S. pneumoniae
Time frame: 24 months of age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
- Derived from this study: PubMed 41442837Toh 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.
- Derived from this study: PubMed 36785850Smith-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.
- Derived from this study: PubMed 34171233Licciardi 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.
- Derived from this study: PubMed 33745731Temple 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.
- Derived from this study: PubMed 30975525Temple 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.
- Derived from this study: PubMed 29884695Temple 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward K Mulholland, MBBS, FRACP principal investigator
Murdoch Childrens Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing PCV10 and PCV13 in people with Pneumococcal Vaccines, run by Murdoch Childrens Research Institute at 1 site in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes (time frame: 4 weeks post-primary series). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01953510, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2022.