Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (Synflorix™) When Administered to Children Who Are at an Increased Risk of Pneumococcal Infection
Condition: Infections, Streptococcal; Streptococcus Pneumoniae Vaccines
MeSH terms: Infections; Communicable Diseases; Pneumonia, Pneumococcal; Pneumococcal Infections; Streptococcal Infections
Intervention: Synflorix™
Intervention description: 1 or 2 doses depending on the priming status, intramuscularly in the non-dominant deltoid muscle or the thigh.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pneumococcal infection; Synflorix; Children; Immunogenicity; Safety

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 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.

        Exclusion Criteria:

          -  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.

          -  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.