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

NCT01746108 | Completed Phase 3 Results

• 2 other identifiers: 1158842011-006013-34
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 6

Brief 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. 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.

Conditions

Infections, Streptococcal; Streptococcus Pneumoniae Vaccines

Keywords

Pneumococcal infection; Synflorix; Children; Immunogenicity; Safety

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  During the 4-day (Days 0-3) after dose 1

Study Arms (4)

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.

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.

Biological: Synflorix™

Healthy-Unprimed Group

ACTIVE COMPARATOR

Subjects who have not been previously vaccinated with any pneumococcal vaccine and are healthy.

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.

Biological: Synflorix™

Interventions

Synflorix™ BIOLOGICAL

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

At-risk-Primed Group; At-risk-Unprimed Group; Healthy-Primed Group; Healthy-Unprimed Group

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Krakow, 31-302, Poland

Location

GSK Investigational Site

Warsaw, 02-127, Poland

Location

GSK Investigational Site

Wroclaw, 50-368, Poland

Location

GSK Investigational Site

Barnaul, 656056, Russia

Location

GSK Investigational Site

Novokuznetsk, 654063, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

Related Publications (1)

• 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.

  PMID: 28866290 BACKGROUND

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Streptococcal Infections; Pneumococcal Infections

Interventions

PHiD-CV vaccine

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 10, 2012
• Study Start: June 18, 2013
• Primary Completion: June 29, 2015
• Study Completion: June 29, 2015
• Last Updated: July 9, 2019
• Results First Posted: January 9, 2017

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

PL (3); RU (3)