Clinical Trial: Immunogenicity and Safety of Kinrix + (Measles Mumps Rubella) MMR Vaccine With and Without Varicella Vaccine in Healthy Children 4-6 Years

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Immunogenicity and Safety Study of Kinrix® Co-administered With Varivax®

Brief Summary: The purpose of the study is to evaluate the immunogenicity and safety of Kinrix when co-administered with varicella (Varivax® [varicella virus vaccine live], Merck and Company) and (measles mumps rubella) MMR vaccines, compared to Kinrix co-administered with MMR vaccine alone. Both Kinrix and the second dose of Varivax are indicated in children 4-6 years of age, and there is great potential for the vaccines to be given concurrently. The aim of this trial is to demonstrate that co-administered Varivax does not negatively affect the immunogenicity or reactogenicity of Kinrix.

Detailed Summary:

Subjects 4-6 years of age will be randomized into two groups to receive either Kinrix, Varivax and M-M-RII on day 0 (Group 1) or Kinrix and M-M-RII on day 0 and Varivax at month 1(Group 2).

All subjects in both groups to provide blood samples prior to vaccination on day 0 and at month 1 (for Group 2, blood sampling is prior to vaccination with Varivax).

Duration of the study will be approximately 6 months for each subject with a safety telephone contact 6 months after vaccinations.


Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of Subjects With Booster Responses to Diphteria and Tetanus [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]

    Anti-diphteria (anti-D) and anti-tetanus (anti-T) booster response was defined as:

    • initially seronegative subjects (sero-) (pre-booster antibody concentration below cut-off of < 0.1 international units per milliliter (IU/mL)) with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥0.4 IU/mL)
    • initially seropositive subjects (sero+) (pre-booster antibody concentration ≥0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination
  • Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL) [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]

    anti-PT, anti-FHA and anti-PRN booster response :

    • initially sero- (pre-booster antibody concentration below cut-off < 5.0 EL.U/mL) with increase of at least four times cut-off one month after vaccination (concentration post-booster ≥20.0 EL.U/mL)
    • initially sero+ with pre-booster antibody con

      Original Primary Outcome: Booster responses for D, T, PT, FHA, and PRN and GMTs for antibodies to poliovirus types 1, 2, and 3 [ Time Frame: One month after booster immunization ]

      Current Secondary Outcome:

      • Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]
        Cut-off value was defined as greater than or equal to 1.0 international units per milliliter (IU/mL).
      • Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]
        Concentrations were expressed as GMCs in IU/mL.
      • GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]
        Concentrations are expressed as GMCs in Enzyme-Linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
      • Number of Subjects With an Anti-polio 1, 2, 3 Booster Response [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]

        Anti-poliovirus 1, anti-poliovirus 2 and anti-poliovirus 3 booster response:

        • initially seronegative subjects (pre-booster antibody titer below cut-off of 8 ED50) with an antibody titer ≥ 32 ED50 one month after vaccination
        • initially seropositive subjects (pre-booster antibody titers ≥ 8 ED50) with an increase at least four times the pre-booster antibody titer one month after vaccination.

        ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. The lowest dilution at which serum samples were tested is 1:8 from which a test was considered positive.

      • Number of Subjects Seroprotected Against Diphteria and Tetanus [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]

        Seroprotection status was defined as:

        • anti-D antibody concentration greater than or equal to 0.1 IU/mL
        • anti-T antibody concentration greater than or equal to 0.1 IU/mL
      • Number of Subjects Protected Against Poliovirus 1, 2 and 3 [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]

        Seroprotection was defined:

        * anti-poliovirus type 1, 2 or 3 antibody titer greater than or equal to 8 ED50.

        ED50 is defined here as the reverse of the dilution resulting in 50% inhibition.

      • Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies [ Time Frame: One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group. ]
        Seropositivity was defined as a concentration greater than or equal to 5.0 EL.U/mL
      • Number of Subjects With Solicited Local and General Symptoms [ Time Frame: Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax ]
        Solicited local symptoms included pain, redness and swelling at the injection site. Solicited general symptoms included fever (temperature equal to or greater than 37.5 degrees Celsius), drowsiness and loss of appetite.
      • Number of Subjects With Unsolicited Adverse Events [ Time Frame: Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax ]
        An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
      • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (from Day 0 to 6 months post-vaccination) ]
        Serious adverse events are medical occurrences that result in death, are 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.


      Original Secondary Outcome:

      • Immunogenicity for anti-D and anti-T antibody concentrations for the defined protocol-specified cut-off, antibody GMCs for anti-D, anti-T, anti-PT, anti-FHA and anti-PRN and booster response for anti-poliovirus types 1, 2, and 3 [ Time Frame: One month after booster immunization ]
      • Seroprotection status for the defined protocol-specified cut-off for anti-D and anti-T antibody concentrations and GMTs for anti-poliovirus types 1, 2, and 3 [ Time Frame: One month after booster immunization ]
      • Seropositivity status for the defined protocol-specified cut-off for anti-PT, anti-FHA, and anti-PRN antibody concentrations [ Time Frame: One month after booster immunization ]
      • Incidence of solicited local and general symptoms [ Time Frame: On Day 0 to Day 3 after booster immunization ]
      • Incidence of unsolicited symptoms [ Time Frame: Up to 31 days (Day through Day 30) after booster immunization ]
      • Occurrence of serious adverse events (SAEs) during the entire study period (from Visit 1 through 6 months post-vaccination) [ Time Frame: One month after booster immunization ]


      Information By: GlaxoSmithKline

      Dates:
      Date Received: March 26, 2009
      Date Started: March 2009
      Date Completion:
      Last Updated: September 26, 2016
      Last Verified: September 2016