Immunogenicity and Safety of GSK Biologicals' Combined Measles-mumps-rubella Vaccine in Volunteers, Seven Years of Age and Older

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of GSK's trivalent MMR (Priorix®), comparing it to Mercks MMR vaccine (M-M-R®II), which is approved for use in the US.

Detailed Description
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This study will evaluate the immunogenicity of GSK's trivalent MMR vaccine (referred to as INV_MMR vaccine) in contrast to the US standard of care (M-M-R®II, Merck and Company, referred to as COM_MMR) when both are used as a second dose in subjects 7 years of age and older. In this study, the INV_MMR vaccine may be administered as a second dose to persons with either a history or formal documentation of at least one dose immunization with any MMR vaccine. This study is intended to support licensure of GSK's MMR vaccine in the US.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Combined Measles-mumps-rubella Vaccine in Subjects Seven Years and Older (209762)

Conditions
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Rubella, Mumps, Measles

Intervention / Treatment
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* Biological: Priorix®
* Biological: Merck's M-M-R®II, Measles, Mumps, and Rubella Virus Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they and/or their parent(s) or Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol. Male or female subjects 7 years of age or older and born after December 31, 1956*. *The only exception to this is health care workers born before 1957 without other evidence of immunity to mumps for which one dose of a live mumps virus vaccine is recommended; therefore this population is eligible for enrollment in this study. For all children 7-17 years of age: Written documentation of prior receipt of 1 dose of MMR vaccine administered on or after the first birthday. For all adults 18 years of age and older: Prior receipt (written or verbal history) of at least one dose of MMR vaccine. Birth in the US. Written informed consent obtained from the subject or from the parent(s)/LAR(s) of the subject (assent will be obtained from subjects who are still legally minors in line with local rules and regulations). Subjects in stable health as determined by investigator's physical examination and assessment of subjects' medical history. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, or ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject Has agreed to be abstinent or practiced adequate contraception during the entire period starting 30 days prior to vaccination(s) until 3 months after receipt of the study vaccination and has a negative pregnancy test on the day of vaccination. Exclusion Criteria: Child in care. For all children 7-17 years of age: Previous receipt of more than 1 dose of a measles-containing vaccine. Use of any investigational or non-registered product other than the study vaccine(s), during the period starting 30 days preceding the day of study vaccination, (i.e. 30 days prior to Day 0) or planned use during the entire study period. Receipt of any measles, mumps or rubella-containing vaccine during the period starting 42 days before the day of study vaccination (i.e. 42 days prior to Day 0). Chronic administration (defined as 14 or more consecutive days) of immunosuppressants or other immune-modifying drugs during the period starting 180 days before study vaccination or any planned administration of immune-modifying drugs during the entire study. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination through the immunogenicity evaluation at Visit 2 or Visit 3 (for one-dose or two-dose cohort, respectively). Planned administration/ administration of any live viral vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination and ending at Visit 2. Live intranasal influenza vaccine or any inactivated vaccine required in the age group may be given at any time, including the day of study vaccination. 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. History of measles, mumps, or rubella disease. Known exposure to measles, mumps, or rubella, during the period starting 30 days before study start (i.e. 30 days prior to Day 0). %

Ages Eligible for Study
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Minimum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INV_MMR Group<br>Subjects will receive 1 dose of GSK Biologicals' trivalent Measles, Mumps, and Rubella Virus Vaccine (Priorix®). | Biological: Priorix®<br>* 1 dose administered as a subcutaneous (SC) injection.<br>|
| Active Comparator: COM_MMR Group<br>Subjects will receive 1 dose of Merck's M-M-R®II, Measles, Mumps, and Rubella Virus Vaccine. | Biological: Merck's M-M-R®II, Measles, Mumps, and Rubella Virus Vaccine<br>* 1 dose administered subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-measles Virus Antibody Concentrations. | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in milli International Units per milliliter (mIU/mL). Seropositivity was defined as subjects with anti-measles virus antibody concentration equal or greater than 150 mIU/mL. | At Day 42 | 
| Anti-mumps Virus Antibody Concentrations | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in EU/mL. Seropositivity was defined as subjects with anti-mumps virus antibody concentration equal or greater than 5 EU/mL | At Day 42 | 
| Anti-rubella Virus Antibody Concentrations. | Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. Seropositivity was defined as subjects with anti-rubella virus antibody concentration equal or greater than 4 IU/mL | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Threshold of 200 mIU/mL (Seroresponse Rate) | Seroresponse was defined as: Anti-measles virus antibody concentration equal to or above the threshold of 200 mIU/mL after administration of INV_MMR vaccine vs. COM_MMR at Day 42. | At Day 42 | 
| Number of Subjects With Anti-mumps Virus Antibody Concentration Equal or Above the Threshold of 10 EU/mL (Seroresponse Rate). | Seroresponse was defined as: Anti-mumps virus antibody concentration equal to or above the threshold of 10 EU/mL after administration of INV_MMR vaccine vs. COM_MMR at Day 42. | At Day 42 | 
| Number of Subjects With Anti-rubella Virus Antibody Concentration Equal or Above the Threshold of 10 IU/mL (Seroresponse Rate). | Seroresponse was defined as: Anti-rubella virus antibody concentration equal to or above the threshold of 10 IU/mL after administration of INV_MMR vaccine vs. COM_MMR at Day 42. | At Day 42 | 
| Number of Subjects Who Achieved a 4-fold or Greater Rise in Anti-measles, Anti-mumps and Anti-rubella Virus Antibody Concentrations. | For subjects with seronegative status at pre-vaccination, a 4-fold rise in antibody concentration is defined as 4 times the cut-off level of the assay. Cut-off levels for anti-measles, anti-mumps and anti-rubella virus antibody concentrations are 150 mIU/mL, 5 EU/mL and 4 IU/mL. | At Day 42 | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any local symptom regardless of their intensity grade. Grade 3 Pain = Significant pain at rest. Prevented normal every day activities. Grade 3 redness = redness with surface diameter >50mm. Grade 3 swelling = swelling with surface diameter >50mm. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects Reporting Fever | Fever was assessed:Any fever (≥38°C) = occurrence of any fever regardless of its intensity grade or relationship to vaccination. Grade3 fever = fever >39.5°C. . Related = symptom assessed by the investigator as causally related to study vaccination.The preferred route for recording temperature in this study was oral. | During the 43 days (Days 0-42) post-vaccination period. | 
| Number of Subjects Reporting Solicited General Symptoms as Parotid/Salivary Gland Swelling and Any Sign of Meningism/Seizure. | Assessed MMR specific symptoms were parotid/salivary gland swelling and any sign of meningism/seizure. Parotid/salivary gland swelling: Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade 3 Parotid/salivary gland swelling = Swelling accompanied with general symptoms. Meningism/seizure: Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination; Grade-3 meningism/seizure= Prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related symptom = symptom assessed by the investigator as causally related to study vaccination. | During the 43 days (Days 0-42) post-vaccination period. | 
| Number of Subjects Reporting Unsolicited AEs | Any untoward medical occurrence in a patient or clinical investigation child, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product | During the 43 days (Days 0-42) post-vaccination period. | 
| Number of Subjects Reporting Solicited Rash Symptom | Assessed any rash, Grade 3, Related, Localized rash, Generalized rash,measles/rubella-rash. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination. Grade3 rash/exanthema= Rash which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Grade 3 measles/rubella/varicella-like rash = Rash with more than150 lesions. Related = symptom assessed by the investigator as causally related to study vaccination. | During the 43 days (Days 0-42) post-vaccination period. | 
| Number of Subjects Reporting Solicited Joint Pain (Arthralgia/Arthritis) | Assessed any, Grade-3, Related. Any= occurrence of any general symptom regardless of its intensity grade or relationship to vaccination; Grade3 joint pain (arthralgia/arthritis)= Pain which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related = symptom assessed by the investigator as causally related to study vaccination. | During the 43 days (Days 0-42) post-vaccination period. | 
| Number of Subjects Reporting NOCDs | Occurrence of new onset chronic diseases (NOCDs) | Day 0 through the end of the study (Day 180) | 
| Number of Subjects Reporting Adverse Events Prompting ER Visits | Occurrence of AEs prompting emergency room (ER) visits. | Day 0 through the end of the study (Day 180) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. | Day 0 through the end of the study (Day 180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Measles, mumps and rubella diseases, Safety, Immunogenicity