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

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00861744

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
Diseases Caused by Measles, Mumps, Rubella and Varicella Viruses	Biological: GSK Biological's investigational vaccine 209762 Biological: M-M-R® II (Merck and Co) Biological: Varivax® Biological: Havrix® Biological: Prevnar®	Phase II

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:

MedlinePlus related topics: Chickenpox Hepatitis Hepatitis A Measles Mumps Rubella Shingles

Drug Information available for: Heptavalent pneumococcal conjugate vaccine Measles-Mumps-Rubella Vaccine Pneumococcal Vaccines Chickenpox Vaccine

U.S. FDA Resources

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: 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).
Number of Subjects With Anti-mumps Virus Antibody Titer Equal to or Above the Cut-off-value. [ Time Frame: 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).
Number of Subjects With Anti-rubella Antobody Concentrations Equal to or Above the Cut-off-value. [ Time Frame: 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: 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 Concentration. [ Time Frame: 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: 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: 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: 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: Day 42 after administration of a dose of Varivax 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 concentration < 25 mIU/mL prior to vaccination.
Anti-hepatitis A Virus Antibody Concentrations. [ Time Frame: 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: 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: Day 0 before vaccination ] [ Designated as safety issue: No ]
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.
Concentrations/Titers of Antibody to Measles, Mumps, Rubella and Varicella [ Time Frame: 1 year post-vaccination ] [ Designated as safety issue: No ]
Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Concentrations/Titers of Antibody to Measles, Mumps, Rubella and Varicella [ Time Frame: 2 years post-vaccination ] [ Designated as safety issue: No ]
Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Anti-measles, Anti-mumps, and Anti-rubella Antibody Titer/Concentration (in the Serum of Subjects Below the Cut-off Before Vaccination) [ Time Frame: 1 year post-vaccination ] [ Designated as safety issue: No ]
Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Anti-measles, Anti-mumps, and Anti-rubella Antibody Titer/Concentration (in the Serum of Subjects Below the Cut-off Before Vaccination) [ Time Frame: 2 years post-vaccination ] [ Designated as safety issue: No ]
Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Number of Subjects Reporting Febrile Convulsions [ Time Frame: Over 43 days after vaccination. ] [ 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 Investigator-confirmed Measles/Rubella-like Rash and Varicella-like Rash. [ Time Frame: Over 43 days after vaccination. ] [ Designated as safety issue: No ]
Number of Subjects Reporting Other Rash. [ Time Frame: Over 43 days after vaccination. ] [ 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 Solicited Local Symptoms. [ Time Frame: 4-days after vaccination (Days 0-3) ] [ Designated as safety issue: No ]
Solicited local symptoms assessed were pain, redness and swelling.
Number of Subjects Reporting Fever. [ Time Frame: Over 15 days and over 43 days after vaccination. ] [ 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 Reporting Investigator-confirmed Parotid/Salivary Gland Swelling. [ Time Frame: Over 43 days after vaccination. ] [ Designated as safety issue: No ]
Swelling with accompanying general symptoms
Number of Subjects With Solicited General Symptoms. [ Time Frame: Over 15 days after vaccination. ] [ Designated as safety issue: No ]
Solicited general symptoms assessed were drowsiness, irritability and loss of appetite.
Number of Subjects Reporting Medically Attended Visit (MAEs) [ Time Frame: Over 43 days after vaccination. ] [ Designated as safety issue: No ]
For each solicited and unsolicited symptom the subject experiences, the subject's parents/guardians was asked if they received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason.
Number of Subjects With Unsolicited Adverse Events (AEs). [ Time Frame: Over 43 days after vaccination ] [ Designated as safety issue: No ]
Unsolicited AE covers any AE 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.
Number of Subjects Reporting New Onset Chronic Illnesses (NOCIs). [ Time Frame: 6 months after vaccination (up to Day 180) ] [ Designated as safety issue: No ]
NOCIs included autoimmune disorders, asthma, type I diabetes, allergies.
Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: 6 months after vaccination (up to Day 180) ] [ Designated as safety issue: No ]
SAEs assessed include medical occurences 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. Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Number of Subjects Reporting Serious Adverse Events (SAEs). [ Time Frame: Between Day 180/Visit 3 and Day 730/Visit 5. ] [ 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. Data were analysed up to Day 42 (active phase). Results for additional time-points will be disclosed when available.
Number of Subjects Reporting Conditions Prompting Emergency Room Visits. [ Time Frame: 6 months after vaccination (up to Day 180) ] [ Designated as safety issue: No ]

Enrollment:	1259
Study Start Date:	June 2009
Estimated Study Completion Date:	August 2012
Primary Completion Date:	July 2011 (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 Prevenar 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 Prevenar 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
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 Prevenar 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
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 Prevenar 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 16 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.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
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:	December 1, 2011
Health Authority:	United States: Food and Drug Administration