Infections, StreptococcalPhase 3NCT01746108

Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection

A Phase 3 study testing Synflorix™ in people with Infections, Streptococcal and Streptococcus Pneumoniae Vaccines, run by GlaxoSmithKline at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the immunogenicity, safety and reactogenicity of GSK Biologicals' 10Pn-PD-DiT vaccine in children aged between 2 and 17 years of age having asplenia, splenic dysfunction or complement deficiencies. Read more about this study

Who is it for?: Ages 2 to 17 yearsHealthy volunteers can take part
Conditions the study is for: Infections, Streptococcal, Streptococcus Pneumoniae Vaccines
What is being tested?: Synflorix™
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 52 participants
Where: 6 sitesin 2 countries
Study dates: 18 Jun 2013to 29 Jun 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 2 to 17 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.
Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrollment.
Female subjects of non-child bearing potential may be enrolled in the study. (Non-child bearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy).
Female subjects of child bearing potential may be enrolled in the study, if the subject:
has practiced adequate contraception for 30 days prior to the first vaccination, and
has a negative pregnancy test on the day of vaccination, and

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has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
Priming status:
Children who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13 will be considered for inclusion in the unprimed groups.
Children who have been previously vaccinated with:
at least one dose of a pneumococcal conjugate vaccine, i.e. either Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13
with plain polysaccharide pneumococcal vaccine more than 2 years and less than 5 years before enrollment.
will be considered for inclusion in the primed groups.
Additional inclusion criteria for the At-risk groups:
A male or female aged between, and including, 2 and 17 years at the time of first vaccination.
For the purpose of this study, at-risk subject is a subject with:
Congenital or acquired asplenia such as anatomic, surgical or functional asplenia or
Splenic dysfunction, chronic gastrointestinal disorders, liver disease, infiltrative disorders, vascular disorder etc or
Note: All individuals who are diagnosed by the investigator as with splenic dysfunction are eligible for enrollment in the At-risk group. When available, investigator will collect medical documentation for reduced splenic function diagnosed with an appropriate technique in the At-risk subject's medical records. No further assessment will be necessary. A maximum of 35 individuals with sickle-cell disease can be enrolled in the At-risk group. These subjects do not require assessment of the splenic function as sickle-cell disease is invariably associated with severe splenic dysfunction.
Complement deficiencies. For all subjects defined as At-risk the Investigator will make all efforts to collect information from the subject/subject's parent(s)/LAR(s) during the interview and/or from previously available medical documentation on the date and conditions which have made a child at-risk of pneumococcal infection and/or the results of tests determining spleen dysfunction or complement deficiency. This should be documented in the medical records of the At-risk subject. No originals/copies of medical documentation are needed.
Additional inclusion criteria for the Healthy group:
A male or female matched (for age and country) to a subject aged 24-59 months from the At-risk group.
Healthy subjects as established by medical history and clinical examination before entering into the study.

Who cannot join

Child in care.
Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine(s) and ending 30 days after*.
In case an emergency mass vaccination for an unforeseen public health threat is organised by the public health authorities, outside the routine immunization program, vaccines can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental recommendations and that a written approval of the Sponsor is provided. Vaccines that are recommended for subjects with an increased risk of bacterial infection, can be administered at any time to the subjects enrolled in the At-risk group.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
History of any neurological disorders or seizures.

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Acute disease and/or fever at the time of enrollment.
History of chronic alcohol consumption and/or drug abuse.
Any confirmed or suspected Human Immunodeficiency virus (HIV) infection, based on medical history and physical examination.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.
Major congenital defects except medical conditions that define an At-risk subject.
Previous vaccination against pneumococcal infection with pneumococcal conjugate vaccine within the last 8 weeks.
Previous vaccination against pneumococcal infection with plain polysaccharide vaccine within the last 2 years.
Additional exclusion criteria for the Healthy group:
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled and topical steroids are allowed.
Serious chronic illness.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Family history of congenital or hereditary immunodeficiency.

Trial locations and contacts

6 sites in 2 countries.

Country

City, postcode or hospital

6 sites in 2 countries

Poland3 sites

GSK Investigational Site
Krakow, 31-302
GSK Investigational Site
Warsaw, 02-127
GSK Investigational Site
Wroclaw, 50-368

Other trials in Poland

Russia3 sites

GSK Investigational Site
Barnaul, 656056
GSK Investigational Site
Novokuznetsk, 654063
GSK Investigational Site
Saint Petersburg, 197022

Other trials in Russia

About this study

Official title: Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection

In addition, this study will include an age-matched control group of healthy children aged 24-59 months in order to descriptively compare the immunogenicity of 10Pn-PD-DiT vaccine in the at-risk population to that of the general, healthy population one month after each pneumococcal vaccination.

Read the detailed description

The protocol has been amended to clarify the definition of priming status to consider for inclusion of subjects in the primed groups.

Conditions: Infections, Streptococcal, Streptococcus Pneumoniae Vaccines
Being tested: Synflorix™
Keywords: Pneumococcal infection, Synflorix, Children, Immunogenicity, Safety
Medical subject headings: Streptococcal Infections, Pneumococcal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Synflorix™Biological
1 or 2 doses depending on the priming status, intramuscularly in the non-dominant deltoid muscle or the thigh.

Study groups in NCT01746108
Study group	Role	What they receive
At-risk-Unprimed Group	Experimental	Subjects who have not been previously vaccinated with any pneumococcal vaccine and are at an increased risk of pneumococcal infection. Receives: Biological: Synflorix™
At-risk-Primed Group	Experimental	Subjects who have been previously vaccinated * with at least one dose of a pneumococcal conjugate vaccine i.e. either Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13. * with plain polysaccharide pneumococcal vaccine more than 2 years and less than 5 years before enrollment. and are at an increased risk of pneumococcal infection. Receives: Biological: Synflorix™
Healthy-Unprimed Group	Active comparator	Subjects who have not been previously vaccinated with any pneumococcal vaccine and are healthy. Receives: Biological: Synflorix™
Healthy-Primed Group	Active comparator	Subjects who have been previously vaccinated with at least one dose of a pneumococcal vaccine and are healthy. Receives: Biological: Synflorix™

What is being measured

The primary outcome is the main question the study is designed to answer.

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1)
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A,
-19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was
≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Measured: One month after Dose 1 (At Month 1)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was
≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Measured: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Concentrations of Antibodies Against Protein D (PD) in the At Risk Primed Group.
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations < 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1)
Concentrations of Antibodies Against Protein D (PD) in the At Risk Unprimed Group.
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations < 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Secondary outcomes (13)

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.
Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.
Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.
Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain =Significant pain at rest. Prevented normal every day activities. Grade 3 redness/swelling = redness/swelling above 50 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.
Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = Significant pain at rest. Prevented normal every day activities. Grade 3 redness/swelling = redness/swelling above 50 millimetre. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.
General AEs = drowsiness, irritability, loss of appetite (loss of appet) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity; irritability = crying that could not be comforted/ prevented normal activity; loss of appetite = not eating at all; fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.
General AEs = drowsiness, irritability, loss of appetite (loss of appet) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity; irritability = crying that could not be comforted/ prevented normal activity; loss of appetite = not eating at all; fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.
General AEs = headache, fatigue, gastrointestinal symptoms (gastro symp) (nausea, vomiting, diarrhoea and/or abdominal pain) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: headache, fatigue and gastrointestinal symptoms = symptoms that prevented normal activity; Fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.
General AEs = headache, fatigue, gastrointestinal symptoms (gastro symp) (nausea, vomiting, diarrhoea and/or abdominal pain) and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Grade 3: headache, fatigue and gastrointestinal symptoms = symptoms that prevented normal activity; Fever > 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. Primed subjects received one dose and Unprimed subjects received two doses.
Measured: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Unsolicited AEs.
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Measured: Within the 31-day (Days 0-30) post- vaccination period
Number of Subjects With Serious Adverse Events (SAEs).
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of study subjects
Measured: From Dose 1 at Month 0 up to study end at Month 1 for primed subjects and at Month 3 for unprimed subjects.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL.
Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. When number of subjects analysed = 1, Lower limit and Upper Limit values were entered as equal to the Geometric mean value. "999999.9" was used as placeholder when Upper Limit value was greater than "1.0E8".
Measured: One month after Dose 1 (At Month 1) and/or one month after Dose 2 (At Month 3)
Concentrations of Antibodies Against Protein D (PD) in the Healthy Unprimed Group.
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations < 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Measured: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Jun 201329 Jun 2015

First posted10 Dec 2012 (estimated)
Study start18 Jun 2013
Primary completion29 Jun 2015
Study completion29 Jun 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infections, StreptococcalStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe 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 3
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01746108
Sponsor's protocol ID: 115884
Other IDs: 2011-006013-34
Status last verified: Jun 2019
First submitted: 28 Nov 2012
Last updated: 9 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

Szenborn L, Osipova IV, Czajka H, Kharit SM, Jackowska T, Francois N, Habib MA, Borys D. Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study. Vaccine. 2017 Sep 25;35(40):5331-5338. doi: 10.1016/j.vaccine.2017.08.039. Epub 2017 Aug 31.
PubMed 28866290

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Infections, Streptococcal trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection
ClinicalTrials.gov ID: NCT01746108
Acronym / sponsor ID: 115884
Conditions: Infections, Streptococcal, Streptococcus Pneumoniae Vaccines
Keywords: Pneumococcal infection, Synflorix, Children, Immunogenicity, Safety
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 18 Jun 2013 (actual)
Primary completion: 29 Jun 2015 (actual)
Study completion: 29 Jun 2015 (actual)
First posted: 10 Dec 2012 (estimated)
Results: Posted 9 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The protocol has been amended to clarify the definition of priming status to consider for inclusion of subjects in the primed groups.

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
At-risk-Unprimed Group	Experimental	Biological: Synflorix™Subjects who have not been previously vaccinated with any pneumococcal vaccine and are at an increased risk of pneumococcal infection.
At-risk-Primed Group	Experimental	Biological: Synflorix™Subjects who have been previously vaccinated * with at least one dose of a pneumococcal conjugate vaccine i.e. either Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13. * with plain polysaccharide pneumococcal vaccine more than 2 years and less than 5 years before enrollment. and are at an increased risk of pneumococcal infection.
Healthy-Unprimed Group	Active comparator	Biological: Synflorix™Subjects who have not been previously vaccinated with any pneumococcal vaccine and are healthy.
Healthy-Primed Group	Active comparator	Biological: Synflorix™Subjects who have been previously vaccinated with at least one dose of a pneumococcal vaccine and are healthy.

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (23 listed)

Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol.
Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrollment.
Female subjects of non-child bearing potential may be enrolled in the study. (Non-child bearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy).
Female subjects of child bearing potential may be enrolled in the study, if the subject:
Children who have not been previously vaccinated with any pneumococcal vaccine, i.e. either plain polysaccharide pneumococcal vaccine, Synflorix (10Pn-PD-DiT), Prevenar or Prevenar13 will be considered for inclusion in the unprimed groups.

Key exclusion criteria (21 listed)

Child in care.
Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine(s) and ending 30 days after*.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
History of any neurological disorders or seizures.

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
Synflorix™1 or 2 doses depending on the priming status, intramuscularly in the non-dominant deltoid muscle or the thigh.	Biological	At-risk-Primed Group, At-risk-Unprimed Group, Healthy-Primed Group, Healthy-Unprimed Group

Primary outcome

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Time frame: One month after Dose 1 (At Month 1)
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per millilitre (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.
Time frame: One month after Dose 1 (At Month 1)
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.
Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.
Concentrations of Antibodies Against Protein D (PD) in the At Risk Primed Group.
Time frame: One month after Dose 1 (At Month 1)
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations < 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.
Concentrations of Antibodies Against Protein D (PD) in the At Risk Unprimed Group.
Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per millilitre (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 153 EL.U/mL. Antibody concentrations < 153 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

13 secondary outcomes

Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.
Time frame: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.
Time frame: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.
Time frame: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any and Severe (Grade 3) Solicited Local Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.
Time frame: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 2 to 4 Years.
Time frame: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 2 to 4 Years.
Time frame: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 1 for Subjects Aged Between 5 to 17 Years.
Time frame: During the 4-day (Days 0-3) after dose 1
Number of Subjects With Any, Severe (Grade 3) and Related Solicited General Adverse Events (AEs) After Dose 2 for Subjects Aged Between 5 to 17 Years.
Time frame: During the 4-day (Days 0-3) after dose 2
Number of Subjects With Unsolicited AEs.
Time frame: Within the 31-day (Days 0-30) post- vaccination period
Number of Subjects With Serious Adverse Events (SAEs).
Time frame: From Dose 1 at Month 0 up to study end at Month 1 for primed subjects and at Month 3 for unprimed subjects.
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.
Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the Healthy Un-primed Group.
Time frame: One month after Dose 1 (At Month 1) and/or one month after Dose 2 (At Month 3)
Concentrations of Antibodies Against Protein D (PD) in the Healthy Unprimed Group.
Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3)

Results and safety

Results posted to the registry on 9 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Synflorix AR-Pr-2-17Y Group	18	18
Synflorix AR-Un-2-17Y Group	28	24
Synflorix HE-Un-2-4Y Group	6	6

Primary outcome: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.

Time frame: One month after Dose 1 (At Month 1). Geometric mean (95% Confidence Interval). Unit: μg/mL

Measure	Synflorix AR-Pr-2-17Y Group n = 18
Anti-1 (N=18)	1.94 (1.4 to 2.69)
Anti-4 (N=18)	6.16 (3.89 to 9.76)
Anti-5 (N=18)	2.44 (1.24 to 4.83)
Anti-6B (N=18)	3.66 (1.93 to 6.96)
Anti-7F (N=18)	3.34 (2.54 to 4.38)
Anti-9V (N=18)	2.87 (1.65 to 4.97)
Anti-14 (N=18)	21.08 (10.97 to 40.52)
Anti-18C (N=18)	10.84 (6.99 to 16.81)

Population analysed: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one pneumococcal vaccine serotype or protein D for at least one blood sample taken after vaccination.

Primary outcome: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.

Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3). Geometric mean (95% Confidence Interval). Unit: μg/mL

Measure	Synflorix AR-Un-2-17Y Group n = 23
Anti-1 Month 1 (N=23)	1.52 (1.13 to 2.06)
Anti-1 Month 3 (N=21)	2.52 (1.87 to 3.4)
Anti-4 Month 1 (N=23)	9.26 (6.62 to 12.95)
Anti-4 Month 3 (N=21)	7.67 (5.59 to 10.53)
Anti-5 Month 1 (N=23)	2.74 (1.6 to 4.69)
Anti-5 Month 3 (N=21)	3.93 (2.46 to 6.27)
Anti-6B Month 1 (N=23)	1.21 (0.59 to 2.46)
Anti-6B Month 3 (N=21)	2.19 (1.26 to 3.8)

Primary outcome: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group.

Time frame: One month after Dose 1 (At Month 1). Geometric mean (95% Confidence Interval). Unit: Titers

Measure	Synflorix AR-Pr-2-17Y Group n = 15
Opsono-1 (N=14)	12.4 (5.3 to 29.3)
Opsono-4 (N=15)	1291.6 (722.5 to 2308.9)
Opsono-5 (N=15)	75.9 (26.9 to 214.2)
Opsono-6B (N=15)	698.1 (348.8 to 1397.2)
Opsono-7F (N=15)	2787.4 (1959.9 to 3964.4)
Opsono-9V (N=15)	1955.3 (1209.8 to 3160.3)
Opsono-14 (N=15)	2495.7 (1220.6 to 5103.1)
Opsono-18C (N=15)	4421.4 (2982.8 to 6553.9)

Primary outcome: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes in the At Risk Un-primed Group.

Time frame: One month after Dose 1 (At Month 1) and one month after Dose 2 (At Month 3). Geometric mean (95% Confidence Interval). Unit: Titers

Measure	Synflorix AR-Un-2-17Y Group n = 17
Opsono-1 Month 1 (N=14)	8.6 (4 to 18.6)
Opsono-1 Month 3 (N=15)	29.1 (12.1 to 70.1)
Opsono-4 Month 1 (N=17)	1497.1 (696.6 to 3217.4)
Opsono-4 Month 3 (N=16)	2657 (1763.5 to 4003.3)
Opsono-5 Month 1 (N=16)	112.5 (49.1 to 258)
Opsono-5 Month 3 (N=16)	212.9 (116 to 390.7)
Opsono-6B Month 1 (N=16)	1188.8 (548.7 to 2575.7)
Opsono-6B Month 3 (N=16)	2384.3 (1483.2 to 3832.8)

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs: from Month 0 up to Study end, Solicited and Unsolicited AEs: within the 31-day post- vaccination period.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Synflorix AR-Pr-2-17Y Group	0 of 18 (0%)	17 of 18 (94.4%)	Not reported
Synflorix HE-Un-2-4Y Group	0 of 6 (0%)	6 of 6 (100%)	Not reported
Synflorix AR-Un-2-17Y Group	1 of 28 (3.6%)	27 of 28 (96.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28866290Szenborn L, Osipova IV, Czajka H, Kharit SM, Jackowska T, Francois N, Habib MA, Borys D. Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study. Vaccine. 2017 Sep 25;35(40):5331-5338. doi: 10.1016/j.vaccine.2017.08.039. Epub 2017 Aug 31.
IPD for this study will be made available via the Clinical Study Data Request site.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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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.

GSK Clinical Trials study director

GlaxoSmithKline

6 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Synflorix™ in people with Infections, Streptococcal and Streptococcus Pneumoniae Vaccines, run by GlaxoSmithKline at 6 sites in 2 countries.

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 23 inclusion and 21 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 9 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Poland, Russia. 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 9 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes in the At Risk Primed Group. (time frame: One month after Dose 1 (At Month 1)). The study lists 6 primary outcomes in all. 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 NCT01746108, which also lists 1 linked publication.

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 9 Jul 2019.