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Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6-12wks of Age

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00808444
First received: December 11, 2008
Last updated: February 6, 2014
Last verified: February 2011
  Purpose

The purpose of the present study is to demonstrate that the changes in the manufacturing process for the commercial lot of the pneumococcal conjugate vaccine GSK1024850A have no clinical impact and that the immune responses are non-inferior to the immune responses induced by the clinical lot. The study will be conducted in Singapore and Malaysia.


Condition Intervention Phase
Infections, Streptococcal
Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)
Biological: Infanrix hexa
Biological: Infanrix-IPV/Hib
Biological: Rotarix
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Non-inferiority of a Commercial Lot of the Pneumococcal Vaccine GSK1024850A Compared to a Clinical Lot.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]

    Concentrations are given as Geometric Mean Concentrations (GMCs) in microgram per milliliter (μg/mL).

    Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.


  • Concentration of Antibody Against Protein D (PD) [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).


Secondary Outcome Measures:
  • Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

  • Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Anti-pneumococcal cross-reactive serotypes were 6A and 19A.

  • Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]

    Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.

    Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.


  • Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]

    Cross-reactive pneumococcal serotypes were 6A and 19A.

    Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8.


  • Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]

    Opsonophagocytic titers were expressed as GMTs.

    Cross-reactive pneumococcal serotypes included 6A and 19A.


  • Poliovirus Types 1, 2 and 3 Titers [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Titers were given as Geometric Mean Titers (GMTs).

  • Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentrations were defined as GMCs in international units per milliter (IU/mL)

  • Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentration was given as GMC in milli international units per milliliter (mIU/mL).

  • Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA) [ Time Frame: 3 months after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentration was expressed as GMC in units per milliliter (U/mL).

  • Occurrence of Serious Adverse Events [ Time Frame: Following vaccination and throughout the entire study period (Month 0 to Month 4) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

  • Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]

    Titers are presented as Geometric Mean Titers (GMTs).

    Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.


  • Number of Subjects With Solicited Local and General Symptoms. [ Time Frame: Within 4 days (day 0-3) after vaccination ] [ Designated as safety issue: No ]

    Solicited local symptoms were pain, redness and swelling.

    Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting.


  • Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentrations are expressed as GMCs in EL.U/mL.

  • Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) [ Time Frame: One month after primary immunization (month 4) ] [ Designated as safety issue: No ]
    Concentrain was expressed as GMC in µg/mL.

  • Occurrence of Unsolicited Adverse Events [ Time Frame: Within 31 days (day 0-30) after vaccination ] [ Designated as safety issue: No ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


Enrollment: 466
Study Start Date: January 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Synflorix Clinical Lot & Infanrix Group
Subjects received 3 doses of the clinical lot of Synflorix TM (GSK1024850A) intramuscularly in the right thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 and 5 months of age in Malaysia or 2 and 5 months of age in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1).
Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)
Intramuscular injection, 3 doses
Biological: Infanrix hexa
Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore
Other Name: DTPa-combined vaccine
Biological: Infanrix-IPV/Hib
Intramuscular injection, only for Visit 2 in Singapore
Other Name: DTPa-combined vaccine
Biological: Rotarix
Oral, 2 doses
Other Name: HRV vaccine
Experimental: Synflorix Commercial Lot Infanrix Group
Subjects received 3 doses of the commercial lot of Synflorix TM (GSK1024850A) intramuscularly in the lright thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 or 5 months of age in Malaysia or 2 and 5 months in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1).
Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)
Intramuscular injection, 3 doses
Biological: Infanrix hexa
Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore
Other Name: DTPa-combined vaccine
Biological: Infanrix-IPV/Hib
Intramuscular injection, only for Visit 2 in Singapore
Other Name: DTPa-combined vaccine
Biological: Rotarix
Oral, 2 doses
Other Name: HRV vaccine

  Eligibility

Ages Eligible for Study:   6 Weeks to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female subjects between, and including 6-12 weeks of age at the time of the first vaccination.
  • Subjects for whom the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol.
  • Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward.
  • Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study).
  • Born after a gestation period of >= 36 to <= 42 weeks.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period.
  • Concurrently participating in another clinical study, at any time during the study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
  • A family history of congenital or hereditary immunodeficiency.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period (with the exception of hepatitis B immunoglobulins at birth).
  • Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of vaccines where the first dose can be given within the first two weeks of life).
  • Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine and ending 7 days after Dose 1 and Dose 2 and 30 days after Dose 3.
  • History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, H. influenzae type b and rotavirus disease.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
  • History of any neurological disorders or seizures.
  • Major congenital defects or serious chronic illness.
  • Acute disease at the time of enrolment.
  • Gastroenteritis within 7 days preceding the study vaccine administration.
  • Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808444

Locations
Malaysia
GSK Investigational Site
Kuala Lumpur, Malaysia, 59100
GSK Investigational Site
Seremban, Negeri Sembilan, Malaysia, 70300
Singapore
GSK Investigational Site
Singapore, Singapore, 229899
GSK Investigational Site
Singapore, Singapore, 119074
GSK Investigational Site
Singapore, Singapore, 149547
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00808444     History of Changes
Other Study ID Numbers: 111654
Study First Received: December 11, 2008
Results First Received: October 25, 2010
Last Updated: February 6, 2014
Health Authority: Malaysia: Ministry of Health
Singapore: Health Sciences Authority

Keywords provided by GlaxoSmithKline:
Pneumococcal vaccine
Immunogenicity
Primary vaccination
Safety
Pneumococcal disease

Additional relevant MeSH terms:
Streptococcal Infections
Bacterial Infections
Gram-Positive Bacterial Infections

ClinicalTrials.gov processed this record on November 25, 2014