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

Measles Clinical Trial

Official title:

A Phase II, Randomized, Observer Blind, Controlled, Multicenter Study to Assess Immunogenicity and Antibody Persistence Following Vaccination With GSK's Candidate Combined Measles, Mumps, and Rubella Vaccine (MMR) Versus M-M-R® II as a First Dose, Both Administered Subcutaneously at 12-15 Months of Age, Concomitantly With Hepatitis A Vaccine (HAV), Varicella Vaccine (VV) and Pneumococcal Conjugate Vaccine (PCV) But at Separate Sites.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00861744
• Other study ID #: 111870
• Secondary ID: 2011-005860-31
• Status: Completed
• Phase: Phase 2
• Start date: June 3, 2009
• Est. completion date: June 18, 2012

Study information

• Verified date: December 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1259
• Est. completion date: June 18, 2012
• Est. primary completion date: July 21, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 15 Months

Eligibility

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.

Related Conditions & MeSH terms

• Measles
• Measles-Mumps-Rubella Vaccine
• Mumps
• Rubella

Intervention

Biological:
• GSK Biological's investigational vaccine 209762
Subcutaneous injection, one dose
• M-M-R® II (Merck and Co)
Subcutaneous injection, one dose
• Varivax®
Subcutaneous injection, one dose
• Havrix®
Intramuscular injection, one dose
• Prevnar®
Intramuscular injection, one dose

Locations

Country	Name	City	State
Puerto Rico	GSK Investigational Site	Bayamon
Puerto Rico	GSK Investigational Site	San Germán
Puerto Rico	GSK Investigational Site	San Juan
United States	GSK Investigational Site	Altamonte Springs	Florida
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Arkansas City	Kansas
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Bardstown	Kentucky
United States	GSK Investigational Site	Bossier City	Louisiana
United States	GSK Investigational Site	Bristol	Tennessee
United States	GSK Investigational Site	Cary	North Carolina
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Conway	Arkansas
United States	GSK Investigational Site	Corpus Christi	Texas
United States	GSK Investigational Site	Dalton	Georgia
United States	GSK Investigational Site	Dayton	Ohio
United States	GSK Investigational Site	DeKalb	Illinois
United States	GSK Investigational Site	Downey	California
United States	GSK Investigational Site	East Norriton	Pennsylvania
United States	GSK Investigational Site	Fall River	Massachusetts
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Great Falls	Montana
United States	GSK Investigational Site	Gresham	Oregon
United States	GSK Investigational Site	Henderson	Nevada
United States	GSK Investigational Site	Huntington	West Virginia
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Layton	Utah
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Nampa	Idaho
United States	GSK Investigational Site	Paramount	California
United States	GSK Investigational Site	Provo	Utah
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rydal	Pennsylvania
United States	GSK Investigational Site	Saint George	Utah
United States	GSK Investigational Site	Santa Ana	California
United States	GSK Investigational Site	Springville	Utah
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Tuscaloosa	Alabama
United States	GSK Investigational Site	Utica	New York
United States	GSK Investigational Site	Virginia Beach	Virginia
United States	GSK Investigational Site	West Covina	California
United States	GSK Investigational Site	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Mufson MA, Diaz C, Leonardi M, Harrison CJ, Grogg S, Carbayo A, Carlo-Torres S, JeanFreau R, Quintero-Del-Rio A, Bautista G, Povey M, Da Costa C, Nicholson O, Innis BL. Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12-15 Months. J Pediatric Infect Dis Soc. 2015 Dec;4(4):339-48. doi: 10.1093/jpids/piu081. Epub 2014 Aug 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value.	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.	At Day 42 after administration of a dose of Priorix vaccine.
Primary	Number of Subjects With Anti-mumps Virus Antibody Titer Equal to or Above the Cut-off-value.	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.	At Day 42 after administration of a dose of Priorix vaccine.
Primary	Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.	Anti-rubella virus antibody cut-off-value assessed was = 10 International Units per milliliter (IU/mL).	At Day 42 after administration of a dose of Priorix vaccine.
Secondary	Number of Subjects With Anti-varicella Antibody Concentration Equal to or Above the Cut-off-value.	Anti-varicella virus antibody cut-off-value assessed was = 75 milli-International Units per milliliter (mIU/mL).	At Day 42 after administration of a dose of Varivax vaccine.
Secondary	Anti-measles Virus Antibody Concentrations	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.	At Day 42 after administration of a dose of Priorix vaccine.
Secondary	Anti-mumps Virus Antibody Concentrations	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.	At Day 42 after administration of a dose of Priorix vaccine.
Secondary	Anti-rubella Virus Antibody Concentrations	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.	At Day 42 after administration of a dose of Priorix vaccine.
Secondary	Anti-S. Pneumoniae Antibody Concentrations (by Serotype).	Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.	At Day 42 after vaccination
Secondary	Anti-varicella Antibody Concentrations.	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.	At Day 42 after administration of a dose of Varivax vaccine.
Secondary	Anti-hepatitis A Virus Antibody Concentrations.	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.	At Day 42 after administration of a dose of Havrix vaccine.
Secondary	Number of Subjects With Anti-hepatitis A Antibody Concentrations Equal to or Above the Cut-off-value.	Anti-hepatitis A antibody cut-off-value assessed was =15 milli-International Units per milliliter (mIU/mL).	At Day 42 after administration of a dose of Havrix vaccine.
Secondary	Anti-S. Pneumoniae Antibody Concentrations (by Serotype).	Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.	At Day 0 before vaccination
Secondary	Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles virus antibody cut-off-value assessed was = 200 milli-International Units per milliliter (mIU/mL).	At 1 year post-vaccination
Secondary	Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Anti-measles virus antibody cut-off-value assessed was = 200 milli-International Units per milliliter (mIU/mL).	At 2 years post-vaccination
Secondary	Anti-measles Virus Antibody Concentrations	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.	At 2 years post-vaccination
Secondary	Anti-measles Virus Antibody Concentrations	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.	At 1 year post-vaccination
Secondary	Number of Subjects Reporting Investigator-confirmed Measles/Rubella-like Rash and Varicella-like Rash.		During the 43-day (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting Febrile Convulsions	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.	During the 43-day (Days 0-42) post-vaccination period
Secondary	Anti-mumps Virus Antibody Titers (Enhanced Plaque Reduction Neutralization (PRN))	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.	At 1 year post-vaccination
Secondary	Number of Subjects Reporting Other Rash.	Other rash = not confirmed by the investigator to be either measles/rubella-like or varicella-like in nature	During the 43-day (Days 0-42) post-vaccination period
Secondary	Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Enhanced PRN)	Anti-mumps virus antibody cut-off-value assessed was = 51 ED50.	At 1 year post-vaccination
Secondary	Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.	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.	At 1 year post-vaccination
Secondary	Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.	Anti-rubella virus antibody cut-off-value assessed was = 10 International Units per milliliter (IU/mL).	At 2 years post-vaccination
Secondary	Anti-rubella Virus Antibody Concentrations	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.	At 1 year post-vaccination
Secondary	Anti-rubella Virus Antibody Concentrations	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.	At 2 years post-vaccination
Secondary	Number of Subjects Reporting Fever.	fever is assessed for temperature =38°C/100.4°F and >39.5°C/103.1°F as measured rectally.	During the 15-day (Days 0-14) and 43 days (Days 0-42) post-vaccination period
Secondary	Number of Subjects With Solicited Local Symptoms.	Solicited local symptoms assessed were pain, redness and swelling.	During the 4-day (Days 0-3) post-vaccination period
Secondary	Number of Subjects Reporting Medically Attended Visit (MAEs)	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.	During the 43-day (Days 0-42) post-vaccination period
Secondary	Number of Subjects With Unsolicited Adverse Events (AEs).	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.	During the 43-day (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting Investigator-confirmed Parotid/Salivary Gland Swelling.	Swelling with accompanying general symptoms	During the 43-day (Days 0-42) post-vaccination period
Secondary	Number of Subjects With Solicited General Symptoms.	Assessed solicited general symptoms were drowsiness, irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade.	During the 15-day (Days 0-14) post-vaccination period
Secondary	Number of Subjects Reporting New Onset Chronic Illnesses (NOCIs).	NOCIs included autoimmune disorders, asthma, type I diabetes, allergies.	From Day 0 to Day 180 after vaccination
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs)	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.	From Day 0 to Day 180 after vaccination
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs).	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.	From Day 180 to Day 730 after vaccination
Secondary	Number of Subjects Reporting Conditions Prompting Emergency Room (ER) Visits.		From Day 0 to Day 180 after vaccination
Secondary	Anti-mumps Virus Antibody Titers (Unenhanced PRN)	Antibody titers were expressed as Geometric Mean Titer (GMT).	At 1 year post-vaccination
Secondary	Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN)	Anti-mumps virus antibody cut-off-value assessed was = 4 Estimated Dose 50 (ED50).	At 1 year post-vaccination
Secondary	Anti-mumps Virus Antibody Titers (Unenhanced PRN)	Antibody concentrations are expressed as Geometric Mean Titer (GMT).	At 2 years post-vaccination
Secondary	Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN)	Anti-mumps virus antibody cut-off-value assessed was = 4 Estimated Dose 50 (ED50).	At 2 years post-vaccination
Secondary	Anti-mumps Virus Antibody Concentrations (Pharmaceutical Product Development (PPD) ELISA)	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.	At 1 year post-vaccination
Secondary	Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA)	Anti-mumps virus antibody cut-off-value assessed was = 10 ELISA units per milliliter (EU/mL)	At 1 year post-vaccination
Secondary	Anti-mumps Virus Antibody Concentrations (PPD ELISA)	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.	At 2 years post-vaccination
Secondary	Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA)	Anti-mumps virus antibody cut-off-value assessed was = 10 ELISA units per milliliter (EU/mL)	At 2 years post-vaccination

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