Immunogenicity of GSKs' MMR Vaccine (209762) vs. M-M-R® II, When Given With Routine Vaccines at 12-15 Months of Age

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00861744
First received: March 12, 2009
Last updated: June 5, 2014
Last verified: September 2013
  Purpose

The purpose of this study is to compare two measles, mumps and rubella conjugate vaccines (manufactured by GSK and Merck and Company ) in terms of the immune response elicited and safety with a six month follow-up after first vaccination. Additionally, antibody persistence will be assessed one and two years after administration of MMR vaccine.

The Protocol Posting has been updated following Protocol amendment 1 and 2, Oct 2009.


Condition Intervention Phase
Rubella
Mumps
Measles
Biological: GSK Biological's investigational vaccine 209762
Biological: M-M-R® II (Merck and Co)
Biological: Varivax®
Biological: Havrix®
Biological: Prevnar®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immunogenicity of GlaxoSmithKline Biologicals' MMR Vaccine (209762) vs. M-M-R® II, When Co-administered With Hepatitis A, Varicella and Pneumococcal Conjugate Vaccines to Children 12-15 Months of Age

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value. [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Anti-measles virus antibody cut-off-value assessed was ≥ 200 milli-International Units per milliliter (mIU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations <150 mIU/mL prior to vaccination.

  • Number of Subjects With Anti-mumps Virus Antibody Titer Equal to or Above the Cut-off-value. [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 51 Estimated Dose 50 (ED50). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations <24 ED50 prior to vaccination.

  • Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value. [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Anti-rubella virus antibody cut-off-value assessed was ≥ 10 International Units per milliliter (IU/mL).


Secondary Outcome Measures:
  • Number of Subjects With Anti-varicella Antibody Concentration Equal to or Above the Cut-off-value. [ Time Frame: At Day 42 after administration of a dose of Varivax vaccine. ] [ Designated as safety issue: No ]
    Anti-varicella virus antibody cut-off-value assessed was ≥ 75 milli-International Units per milliliter (mIU/mL).

  • Anti-measles Virus Antibody Concentrations [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations <150 mIU/mL prior to vaccination.

  • Anti-mumps Virus Antibody Concentrations [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Titer (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody titer < 24 ED50 prior to vaccination.

  • Anti-rubella Virus Antibody Concentrations [ Time Frame: At Day 42 after administration of a dose of Priorix vaccine. ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <4 IU/mL prior to vaccination.

  • Anti-S. Pneumoniae Antibody Concentrations (by Serotype). [ Time Frame: At Day 42 after vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.

  • Anti-varicella Antibody Concentrations. [ Time Frame: At Day 42 after administration of a dose of Varivax vaccine. ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Titers (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody concentration < 25 mIU/mL prior to vaccination.

  • Anti-hepatitis A Virus Antibody Concentrations. [ Time Frame: At Day 42 after administration of a dose of Havrix vaccine. ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-hepatitis A virus antibody concentrations <15 mIU/mL prior to vaccination.

  • Number of Subjects With Anti-hepatitis A Antibody Concentrations Equal to or Above the Cut-off-value. [ Time Frame: At Day 42 after administration of a dose of Havrix vaccine. ] [ Designated as safety issue: No ]
    Anti-hepatitis A antibody cut-off-value assessed was ≥15 milli-International Units per milliliter (mIU/mL).

  • Anti-S. Pneumoniae Antibody Concentrations (by Serotype). [ Time Frame: At Day 0 before vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.

  • Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Anti-measles virus antibody cut-off-value assessed was ≥ 200 milli-International Units per milliliter (mIU/mL).

  • Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Anti-measles virus antibody cut-off-value assessed was ≥ 200 milli-International Units per milliliter (mIU/mL).

  • Anti-measles Virus Antibody Concentrations [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations <150 mIU/mL prior to vaccination.

  • Anti-measles Virus Antibody Concentrations [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations <150 mIU/mL prior to vaccination.

  • Number of Subjects Reporting Investigator-confirmed Measles/Rubella-like Rash and Varicella-like Rash. [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
  • Anti-mumps Virus Antibody Titers (Enhanced Plaque Reduction Neutralization (PRN)) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric Mean Titer (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody titer < 24 ED50 prior to vaccination.

  • Number of Subjects Reporting Febrile Convulsions [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    Timing of febrile convulsions: events occured on Day 29 in the Priorix 2 Group and Day 0 in the MMR II Group. All cases of febrile convulsions were case of meningism.

  • Number of Subjects Reporting Other Rash. [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    Other rash = not confirmed by the investigator to be either measles/rubella-like or varicella-like in nature

  • Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Enhanced PRN) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 51 ED50.

  • Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value. [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Anti-rubella virus antibody cut-off-value assessed was ≥ 10 International Units per milliliter (IU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <4 IU/mL prior to vaccination.

  • Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value. [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Anti-rubella virus antibody cut-off-value assessed was ≥ 10 International Units per milliliter (IU/mL).

  • Anti-rubella Virus Antibody Concentrations [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <4 IU/mL prior to vaccination.

  • Anti-rubella Virus Antibody Concentrations [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <4 IU/mL prior to vaccination.

  • Number of Subjects Reporting Fever. [ Time Frame: During the 15-day (Days 0-14) and 43 days (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    fever is assessed for temperature ≥38°C/100.4°F and >39.5°C/103.1°F as measured rectally.

  • Number of Subjects With Solicited Local Symptoms. [ Time Frame: During the 4-day (Days 0-3) post-vaccination period ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling.

  • Number of Subjects Reporting Medically Attended Visit (MAEs) [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.

  • Number of Subjects With Unsolicited Adverse Events (AEs). [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  • Number of Subjects Reporting Investigator-confirmed Parotid/Salivary Gland Swelling. [ Time Frame: During the 43-day (Days 0-42) post-vaccination period ] [ Designated as safety issue: No ]
    Swelling with accompanying general symptoms

  • Number of Subjects With Solicited General Symptoms. [ Time Frame: During the 15-day (Days 0-14) post-vaccination period ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were drowsiness, irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade.

  • Number of Subjects Reporting New Onset Chronic Illnesses (NOCIs). [ Time Frame: From Day 0 to Day 180 after vaccination ] [ Designated as safety issue: No ]
    NOCIs included autoimmune disorders, asthma, type I diabetes, allergies.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From Day 0 to Day 180 after vaccination ] [ Designated as safety issue: No ]
    SAEs assessed include 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs). [ Time Frame: From Day 180 to Day 730 after vaccination ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are congenital anomaly/birth defect in the offspring of a study subject.

  • Number of Subjects Reporting Conditions Prompting Emergency Room (ER) Visits. [ Time Frame: From Day 0 to Day 180 after vaccination ] [ Designated as safety issue: No ]
  • Anti-mumps Virus Antibody Titers (Unenhanced PRN) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric Mean Titer (GMT).

  • Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 4 Estimated Dose 50 (ED50).

  • Anti-mumps Virus Antibody Titers (Unenhanced PRN) [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Titer (GMT).

  • Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN) [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 4 Estimated Dose 50 (ED50).

  • Anti-mumps Virus Antibody Concentrations (Pharmaceutical Product Development (PPD) ELISA) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMC) in ELISA units per milliliter (EU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <5 EU/mL prior to vaccination.

  • Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA) [ Time Frame: At 1 year post-vaccination ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 10 ELISA units per milliliter (EU/mL)

  • Anti-mumps Virus Antibody Concentrations (PPD ELISA) [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMC) in ELISA units per milliliter (EU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations <5 EU/mL prior to vaccination.

  • Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA) [ Time Frame: At 2 years post-vaccination ] [ Designated as safety issue: No ]
    Anti-mumps virus antibody cut-off-value assessed was ≥ 10 ELISA units per milliliter (EU/mL)


Enrollment: 1259
Study Start Date: June 2009
Study Completion Date: May 2012
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Priorix 1 Group
Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 1) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Biological: GSK Biological's investigational vaccine 209762
Subcutaneous injection, one dose
Biological: Varivax®
Subcutaneous injection, one dose
Biological: Havrix®
Intramuscular injection, one dose
Biological: Prevnar®
Intramuscular injection, one dose
Experimental: Priorix 2 Group
Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 2) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Biological: GSK Biological's investigational vaccine 209762
Subcutaneous injection, one dose
Biological: Varivax®
Subcutaneous injection, one dose
Biological: Havrix®
Intramuscular injection, one dose
Biological: Prevnar®
Intramuscular injection, one dose
Experimental: Priorix 3 Group
Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 3) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Biological: GSK Biological's investigational vaccine 209762
Subcutaneous injection, one dose
Biological: Varivax®
Subcutaneous injection, one dose
Biological: Havrix®
Intramuscular injection, one dose
Biological: Prevnar®
Intramuscular injection, one dose
Active Comparator: MMR-II Group
Subjects between 12 and 15 months of age at the time of study vaccination who randomly received one dose of one of three different commercially-available lot of M-M-R II (Merck and Co.) vaccine subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Biological: M-M-R® II (Merck and Co)
Subcutaneous injection, one dose
Biological: Varivax®
Subcutaneous injection, one dose
Biological: Havrix®
Intramuscular injection, one dose
Biological: Prevnar®
Intramuscular injection, one dose

  Eligibility

Ages Eligible for Study:   12 Months to 15 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects for whom the investigator believes their parents/guardians can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study.
  • Male or female between 12 and 15 months of age (e.g. from age 12 months until the day before age 16 months) at the time of vaccination.
  • Written informed consent obtained from the parent/guardian of the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Have previously received three doses of 7-valent pneumococcal conjugate vaccine within the first year of life with the third dose administered at least 30 days prior to enrolment and vaccination with study vaccines.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • 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).
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol from 30 days prior to vaccination until 42 days after vaccination, except for influenza vaccine and Hib vaccine.
  • Previous vaccination against measles, mumps, rubella and/or varicella.
  • Previous vaccination against hepatitis A or receipt of a fourth dose of pneumococcal conjugate vaccine.
  • History of measles, mumps, rubella, varicella/zoster and hepatitis A diseases.
  • Known exposure to measles, mumps, rubella and/or varicella/zoster within 30 days prior to the start of the study.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required), including human immunodeficiency virus (HIV) infection.
  • A family history of congenital or hereditary immunodeficiency.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
  • Hypersensitivity to latex
  • Major congenital defects or serious chronic illness.
  • History of any neurologic disorders or seizures, including febrile seizures.
  • Acute disease at the time of enrolment.
  • Administration of polyclonal immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period.
  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: NCT00861744

  Show 48 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00861744     History of Changes
Other Study ID Numbers: 111870
Study First Received: March 12, 2009
Results First Received: July 14, 2011
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Measles, Mumps, Rubella, Varicella Vaccine
Children
Immunogenicity
Safety
Humans
Combined Vaccine
Vaccines

Additional relevant MeSH terms:
Measles
Mumps
Rubella
Morbillivirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Rubulavirus Infections
Parotitis
Parotid Diseases
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Rubivirus Infections
Togaviridae Infections

ClinicalTrials.gov processed this record on August 21, 2014