Clinical Trial: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life

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

Official Title: Immunogenicity and Safety Study of GSK Biologicals' Priorix® Vaccine (209762) at an End of Shelf-life Potency Compared to Merck & Co., Inc.'s Measles-mumps-rubell

Brief Summary: The purpose of this study is to evaluate end of shelf-life potency in terms of the immunogenicity and safety of GSK Biologicals' trivalent MMR vaccine, by comparing it to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

Detailed Summary: This trial is a Phase IIIA, randomized, observer-blind, controlled, multi-center, multi-country study with four parallel groups. This study will evaluate the immunogenicity and safety of GSK Biologicals' trivalent investigational MMR vaccine (referred to as Inv_MMR vaccine, throughout this document) in contrast to the US standard of care comparator vaccine (M M R®II, Merck and Co., Inc., referred to as Com_MMR throughout this document) in children during their second year of life. The first dose of this two-dose study is designed to establish the end of shelf-life potency of Inv_MMR vaccine. The Inv_MMR vaccine will be given as one of two lots; one of a minimum potency, designated Inv_MMR_Min; and the other at a mid-range or medium potency designated Inv_MMR_Med to two groups. The second dose for both of these Inv_MMR groups will have a potency within the release range of the marketed vaccine. The Com_MMR vaccine will consist of two lots designated Com_MMR_L1 and Com_MMR_L2 and will be analyzed as pooled lots within the study. The first MMR vaccine dose will be co-administered with Varivax, Havrix and (in the US sub-cohort only) Prevnar 13 which are routinely administered to children of this age in the US.
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of subjects with anti-measles virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 42 ]
    Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 mIU/mL.
  • Number of subjects with anti-mumps virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 42 ]
    Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL.
  • Number of subjects with anti-mumps virus antibody concentration (by Plaque Reduction Neutralization Test [PRNT]) equal to or above the cut-off-value [ Time Frame: At Day 42 ]
    Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 4 ED50.
  • Number of subjects with anti-rubella virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 42 ]
    Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL.
  • Anti-measles virus antibody concentrations [ Time Frame: At Day 42 ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL
  • Anti-mumps virus antibody concentrations [ Time Frame: At Day 42 ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL
  • Anti-mumps virus a

    Original Primary Outcome: Immunogenicity of the MMR vaccines [ Time Frame: At Day 42 ]

    Seroresponses for MMR are defined as a post-vacc., anti-virus Ab conc. in children who were seronegative pre-vacc. as follows: For measles virus, a post-vacc. anti-measles virus Ab conc. of ≥200 mIU/mL (ELISA) in children <150 mIU/mL pre-vacc.; For mumps virus, a post-vacc. anti-mumps virus Ab conc. ≥10 EU/mL (ELISA) in children <5 EU/mL pre-vacc.; For mumps virus as measured by PRNT, a post-vacc. anti-mumps virus Ab conc. ≥4 ED50 (PRNT) in children <2.5 ED50 before Dose 1; For rubella virus, a post-vacc. anti-rubella virus Ab conc. ≥10 IU/mL (ELISA) in children <4 IU/mL pre-vacc.


    Current Secondary Outcome:

    • Number of subjects with anti-measles virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 84 ]
      Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 mIU/mL.
    • Number of subjects with anti-mumps virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 84 ]
      Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL.
    • Number of subjects with anti-rubella virus antibody concentration equal to or above the cut-off-value [ Time Frame: At Day 84 ]
      Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL.
    • Anti-measles virus antibody concentrations [ Time Frame: At Day 84 ]
      Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL
    • Anti-mumps virus antibody concentrations [ Time Frame: At Day 84 ]
      Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL
    • Anti-rubella virus antibody concentrations [ Time Frame: At Day 84 ]
      Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL
    • Number of subjects with solicited local symptoms (post dose-1) [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
      Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Cried when limb was moved/spontaneously painful. Prevented normal every day activities.
    • Number of subjects with solicited local symptoms (Post dose-2) [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ]
      Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Cried when limb was moved/spontaneously painful. Prevented normal every day activities.
    • Number of subjects with solicited general symptoms [ Time Frame: 15-day (Days 0-14) post-vaccination period ]
      Assessed solicited general symptoms were Drowsiness, Irritability/fussiness, and loss of appetite. Any= occurrence of any general symptom regardless of intensity grade or relationship to vaccination, Grade 3 drowsiness = symptom that prevented normal activity, Grade 3 irritability/fussiness =crying that could not be comforted/ symptom that prevented normal activity, Grade 3 loss of appetite = did not eat at all.
    • Number of subjects reporting fever (Post dose-1) [ Time Frame: During the 43 days (Days 0-42) post-vaccination period ]
      Fever was assessed for temperature ≥ 38°C, > 39.5°C and related. Related = event assessed by the investigator as causally related to the study vaccination.
    • Number of subjects reporting fever (post dose-2) [ Time Frame: During the 43 days (Days 0-42) post-vaccination period. ]
      Fever was assessed for temperature ≥ 38°C, > 39.5°C and related. Related = event assessed by the investigator as causally related to the study vaccination.
    • Number of subjects reporting MMR specific solicited general symptoms (Post dose-1) [ Time Frame: 43-day (Days 0-42) post-vaccination period ]
      Assessed MMR specific symptoms were parotid gland swelling and any suspected signs of meningism including febrile convulsions. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination, Grade 3 Febrile convulsion = Prevented normal, everyday activity, Grade 3 Parotid gland = Swelling with accompanied general symptoms, Related = event assessed by the investigator as causally related to the study vaccination.
    • Number of subjects reporting MMR specific solicited general symptoms (post dose-2) [ Time Frame: 43-day (Days 0-42) post-vaccination period ]
      Assessed MMR specific symptoms were parotid gland swelling and any suspected signs of meningism including febrile convulsions. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination, Grade 3 Febrile convulsion = Prevented normal, everyday activity, Grade 3 Parotid gland = Swelling with accompanied general symptoms, Related = event assessed by the investigator as causally related to the study vaccination.
    • Number of subjects reporting rash (post dose-1) [ Time Frame: During the 43 days (Days 0-42) post-vaccination period ]
      Assessed any rash, Grade 3, related, localized rash, generalized rash, measles/rubella like rash, and Varicella like rash. Any = occurrence of any general symptom re

      Original Secondary Outcome:

      • Immunogenicity of the MMR vaccines post-dose 2 (US post-dose 2 sub-cohort) in terms of antibody concentration. [ Time Frame: At Day 84 ]
      • Occurrence of solicited local symptoms. [ Time Frame: Days 0-3 ]
      • Occurrence of solicited general symptoms. [ Time Frame: Days 0-42 ]
      • Occurrence of Unsolicited adverse events. [ Time Frame: Days 0-42 ]
      • Occurrence of Adverse events of specific interest. [ Time Frame: From Day 0 through the end of study (Day 222) ]
      • Serious adverse events (SAEs). [ Time Frame: From Day 0 through the end of study (Day 222) ]


      Information By: GlaxoSmithKline

      Dates:
      Date Received: September 6, 2012
      Date Started: October 2012
      Date Completion:
      Last Updated: November 28, 2016
      Last Verified: November 2016