Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' Measles, Mumps and Rubella (MMR) Vaccine (209762) Compared to Merck & Co., Inc.'s MMR Vaccine in Healthy Children 12 to 15 Months of Age

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 Biologicals' trivalent MMR (Priorix), comparing it to Merck's MMR vaccine (M-M-R II), which is approved for use in the US in healthy children 12 to 15 months of age.

Detailed Description
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This study will evaluate the safety of GSK's trivalent MMR vaccine (referred to as INV_MMR vaccine) at a potency that will be used to define maximum release limits for the INV_MMR in comparison to the US standard of care (M-M-R II/ M-M-R VaxPro vaccine referred to as COM_MMR vaccine). In order to obtain more representative data on the comparator vaccine, the COM_MMR used in this study will consist of two lots designated COM_MMR_L1 and COM_MMR_L2. Throughout the study COM_MMR_L1 and COM_MMR_L2 will be analyzed as pooled lots. This study is intended to support licensure of GSK's MMR vaccine in the US. All children will receive Varivax and Havrix vaccines, concomitantly with MMR containing vaccine at 12 to 15 months of age. Prevnar 13 will be administered only to US children. At the end of the study, GSK will provide a second dose of Havrix and/or varicella vaccine to participants enrolled in selected non-US countries if local health departments do not routinely provide hepatitis A and varicella vaccination. The second dose of Havrix and varicella vaccine is not part of the study procedures.

Official Title
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Safety and Immunogenicity Study of GSK Biologicals' Measles-mumps-rubella (MMR) Vaccine (209762) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine, in Healthy Children 12 to 15 Months of Age

Conditions
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Measles; Mumps; Rubella, Measles-Mumps-Rubella Vaccine

Intervention / Treatment
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* Biological: Priorix
* Biological: M-M-R II
* Biological: Varivax
* Biological: Havrix
* Biological: Prevnar 13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female child between 12 and 15 months of age (e.g., from the 1 year birthday until the day before age 16 months) at the time of vaccination. Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol. Written informed consent obtained from the parent(s)/LAR(s) of the child. Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history. For US children only: a child who received all routine vaccinations as per ACIP recommendations prior to study entry: completion of hepatitis B and rotavirus series and completion of the primary series of diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b (Hib) and pneumococcal vaccines. The 3-dose infant series of Prevnar 13 should be completed at least 60 days prior to study vaccination. Exclusion Criteria: Child in care. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Day 0) or planned use during the entire study period. Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Chronic administration (defined as 14 or more consecutive days) of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the study vaccination at Visit 1 or any planned administration of immunosuppressive and immune-modifying drugs during the entire study. For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day or equivalent. Inhaled and topical steroids are allowed. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to the day of study vaccination at Visit 1 and ending at Visit 2. Please Note: Inactivated influenza (Flu) vaccine and monovalent Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s). Any other age appropriate vaccine may be given starting at Visit 2 and anytime thereafter. Administration of immunoglobulins and/or any blood products during the period starting 180 days before the study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2. History of measles, mumps, rubella, varicella/zoster and/or hepatitis A disease. Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting within 30 days prior to first study vaccination. Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin. Acute disease at the time of enrollment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever). Fever is defined as temperature ≥38.0°C/100.4°F by any age appropriate route. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever. Active untreated tuberculosis based on medical history. Any other condition which, in the opinion of the investigator, prevents the child from participating in the study. For US children only: a child that previously received a fourth dose of PCV-13 vaccine.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 15 Months

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<br>Subjects receive 1 dose of the study vaccine Priorix co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also receive Prevnar 13 at Day 0. | Biological: Priorix<br>* 1 dose administered subcutaneously in the triceps region of left arm at Day 0<br>* Other names: mumps and rubella (MMR) vaccine;Biological: Varivax<br>* 1 dose administered subcutaneously in the triceps region of right arm at Day 0<br>* Other names: live;Biological: Havrix<br>* 1 dose administered intramuscularly in the anterolateral region of the right thigh at Day 0<br>* Other names: inactivated;Biological: Prevnar 13<br>* 1 dose administered intramuscularly in the anterolateral region of the left thigh at Day 0 to subjects recruited in US<br>* Other names: Pfizer Inc.'s Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein);|
| Active Comparator: COM_MMR<br>Subjects receive 1 dose of the licensed vaccine M-M-R II or M-M-R VaxPro Lot 1 or Lot 2 co-administered with Varivax and Havrix vaccines at Day 0. Subjects recruited in the US also receive Prevnar 13 at Day 0. | Biological: M-M-R II<br>* 1 dose administered subcutaneously in the triceps region of left arm at Day 0<br>* Other names: Sanofi Pasteur/Merck Sharp and Dohme [SPMSD]);Biological: Varivax<br>* 1 dose administered subcutaneously in the triceps region of right arm at Day 0<br>* Other names: live;Biological: Havrix<br>* 1 dose administered intramuscularly in the anterolateral region of the right thigh at Day 0<br>* Other names: inactivated;Biological: Prevnar 13<br>* 1 dose administered intramuscularly in the anterolateral region of the left thigh at Day 0 to subjects recruited in US<br>* Other names: Pfizer Inc.'s Pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Fever After MMR (Priorix or M-M-R II/M-M-R VaxPro [Lot 1 or Lot 2]) Vaccination | Fever was assessed for temperature equal to/above (≥) 38.0°C and above (>) 39.0°C. The safety profile for fever was assessed based on the group difference (INV_MMR minus COM_MMR) in incidence of fever equal to or below the cut-off value. | During Day 5 to Day 12 post-vaccination period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value | Seroresponse was defined as post-vaccination anti-measles virus antibody concentration greater than or equal to [≥] 200 milli International Units per milliliter [mIU/mL] (Enzyme-Linked Immunosorbent Assay [ELISA], Enzygnost) among subjects who were seronegative (antibody concentration less than [<] 150 mIU/mL) before vaccination. | At Day 42 post vaccination | 
| Anti-measles Virus Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. Analyses included initially seronegative subjects only. | At Day 42 post vaccination | 
| Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value | Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 ELISA Unit per milliliter [EU/mL] (ELISA, Pharmaceutical Product Development, Inc.[PPD]) among subjects who were seronegative (antibody concentration < 5 EU/mL) before vaccination. | At Day 42 post vaccination | 
| Anti-mumps Virus Antibody Concentrations | Antibody concentrations were expressed as GMCs in EU/mL. Analyses included initially seronegative subjects only. | At Day 42 post vaccination | 
| Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value | Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 International Unit per milliliter [IU/mL] (ELISA, Enzygnost) among subjects who were seronegative (antibody concentration < 4 IU/mL) before vaccination. | At Day 42 post vaccination | 
| Anti-rubella Virus Antibody Concentrations | Antibody concentrations were expressed as GMCs in IU/mL. Analyses included initially seronegative subjects only. | At Day 42 post vaccination | 
| Number of Subjects With Any Solicited Local Adverse Events (AEs) | Assessed solicited local AEs were injection site pain, redness and swelling. Any = Occurrence of AE regardless of intensity grade or relation to vaccination. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects With Any Solicited General AEs | Assessed solicited general AEs were drowsiness, irritability/fussiness and loss of appetite. Any = Occurrence of AE regardless of intensity grade or relation to vaccination. | During the 15-day (Days 0-14) post-vaccination period | 
| Number of Subjects Reporting Any Fever | Any fever (≥ 38°C) = Occurrence of fever regardless of intensity grade or relation to vaccination. | During the 43-day (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting Any Rash | Any rash = Occurrence of AE regardless of intensity grade or relation to vaccination. | During the 43-day (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting MMR Specific Solicited General AEs | Assessed MMR specific solicited general AEs were parotid gland swelling and any suspected signs of meningism including febrile convulsions. Any = Occurrence of AE regardless of intensity grade or relation to vaccination. | During the 43-day (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting Any Unsolicited AEs | Unsolicited AE included any AE reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of AE regardless of intensity grade or relation to vaccination. | During the 43-day (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting AEs of Specific Interest | AEs of specific interest included new onset chronic disease (NOCD) (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) and AEs prompting emergency room (ER) visits. | Day 0 through the end of the study (Day 180) | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | SAE included any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. Any = Occurrence of AE regardless of intensity grade or relation to vaccination. | Day 0 through the end of the study (Day 180) | 
| Number of Subjects Reporting Measles-like Illness | Measles-like illness was defined as the occurrence of the following signs/symptoms in the absence of another confirmed diagnosis: maculopapular rash (includes measles/rubella-like rash), fever (≥ 38°C) and at least one of the symptoms: cough, coryza (runny nose), conjunctivitis or diarrhea, with fever or rash. Other event must be one of cough, coryza, conjunctivitis, or diarrhea. | During Day 5 to Day 12 post-vaccination period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rubella, Healthy children, Measles, Safety, Mumps, 12 to 15 months, Immunogenicity