Consistency Study of GlaxoSmithKline (GSK) Biologicals' MMR Vaccine (209762) (Priorix) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine (M-M-R II), in 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 consistency in terms of the immune response to three different lots of GSK Biologicals' trivalent MMR vaccine manufactured to target potencies, and compare its immunogenicity to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

Detailed Description
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This study will evaluate the consistency of the immune response to three different lots of GSK Biologicals' trivalent investigational MMR vaccine (referred to as INV_MMR vaccine, throughout this document) and compare its immunogenicity to the US standard of care comparator vaccine (M-M-R II, Merck and Co., Inc., referred to as COM_MMR throughout this document) in children during their second year of life. The INV_MMR vaccine will be given as one of three consistency lots manufactured to target potencies designated as INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3. The COM_MMR vaccine will be given as one of two lots designated COM_MMR_L1 and COM_MMR_L2 and will be analysed as pooled lots within the study. The MMR vaccine will be co-administered with Varivax (VV), Havrix (HAV) and (in the US sub-cohort only) Prevnar 13 (PCV-13) which are routinely administered to children of this age in the US.

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

Conditions
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Rubella, Measles, Mumps

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 at the time of vaccination. The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, 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: • Child that previously received a 3-dose series of Prevnar 13 only (i.e., no doses given as Prevnar/Prevenar), with the last dose at least 60 days prior to study entry. Exclusion Criteria: Child in care. Use of any investigational or non-registered product 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. Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose 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 study vaccination at Visit 1 and ending at Visit 2. Please Note: Inactivated influenza (Flu) vaccine and 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 prior to 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. 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. Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems. Acute disease at the time of enrollment. 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: Child that previously received a vaccination with heptavalent Prevnar/Prevenar (prior vaccination should be with 3 doses of Prevnar 13 only). Child that previously received a fourth dose of any pneumococcal conjugate 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INV_MMR_L1 Group<br>Subjects receive 1 dose of GSK's candidate combined measles, mumps and rubella (MMR) investigational vaccine (INV_MMR) Lot 1 (L1) co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects are also given PCV-13 vaccine. The MMR vaccine is administered subcutaneously in the triceps region of the left arm while the VV vaccine is administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively. | Biological: Priorix<br>* Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.<br>* Other names: mumps and rubella vaccine (GSK209762);Biological: Varivax<br>* Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.<br>Biological: Havrix<br>* Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.<br>Biological: Prevnar 13<br>* US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.<br>|
| Experimental: INV_MMR_L2 Group<br>Subjects receive 1 dose of GSK's candidate combined measles, mumps and rubella (MMR) investigational vaccine (INV_MMR) Lot 2 (L2) co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects are also given PCV-13 vaccine. The MMR vaccine is administered subcutaneously in the triceps region of the left arm while the VV vaccine is administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively. | Biological: Priorix<br>* Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.<br>* Other names: mumps and rubella vaccine (GSK209762);Biological: Varivax<br>* Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.<br>Biological: Havrix<br>* Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.<br>Biological: Prevnar 13<br>* US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.<br>|
| Experimental: INV_MMR_L3 Group<br>Subjects receive 1 dose of GSK's candidate combined measles, mumps and rubella (MMR) investigational vaccine (INV_MMR) Lot 3 (L3) co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects are also given PCV-13 vaccine. The MMR vaccine is administered subcutaneously in the triceps region of the left arm while the VV vaccine is administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively. | Biological: Priorix<br>* Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.<br>* Other names: mumps and rubella vaccine (GSK209762);Biological: Varivax<br>* Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.<br>Biological: Havrix<br>* Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.<br>Biological: Prevnar 13<br>* US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.<br>|
| Active Comparator: COM_MMR Group<br>Subjects receive 1 dose of COM_MMR Lot 1 and Lot 2 co-administered with VV and HAV vaccines at Visit 1 (Day 0). All US subjects are also given PCV-13 vaccine. The MMR vaccine is administered subcutaneously in the triceps region of the left arm while the VV vaccine is administered subcutaneously in the triceps region of the right arm. HAV and PCV-13 vaccines are administered intramuscularly in the anterolateral region of the right and left thigh, respectively. Pooled analysis is conducted for this group. | Biological: M-M-R II<br>* Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.<br>Biological: Varivax<br>* Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.<br>Biological: Havrix<br>* Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.<br>Biological: Prevnar 13<br>* US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.<br>|

What is the study measuring?
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Primary 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 ≥200 milli International Unit/Milliliter (mIU/mL) among subjects who were seronegative (antibody concentration <150 mIU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| Anti-measles Virus Antibody Concentrations | Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| 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/Milliliter (EU/mL) among subjects who were seronegative (antibody concentrations <5 EU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| Anti-mumps Virus Antibody Concentration | Antibody concentrations were expressed as GMCs in EU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| 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/Milliliter (IU/mL) among subjects who were seronegative (antibody concentrations <4 IU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| Anti-rubella Virus Antibody Concentration | Antibody concentrations were expressed as GMCs in IU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine. | At Day 42 | 
| Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups | Seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥200 mIU/mL among subjects who were seronegative (antibody concentration <150 mIU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV_MMR in terms of seroresponse rates to measles virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV_MMR lots is ≥90% for antibodies to measles virus. | At Day 42 | 
| Anti-measles Virus Antibody Concentrations in Pooled MMR Groups | Antibody concentrations were expressed as GMCs in mIU/mL. | At Day 42 | 
| Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups | Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥10 EU/mL among subjects who were seronegative (antibody concentrations <5 EU/mL) before vaccination. | At Day 42 | 
| Anti-mumps Virus Antibody Concentration in Pooled MMR Groups | Antibody concentrations were expressed as GMCs in EU/mL. | At Day 42 | 
| Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups | Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥10 IU/mL among subjects who were seronegative (antibody concentrations <4 IU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV_MMR in terms of seroresponse rates to rubella virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV_MMR lots is ≥90% for antibodies to rubella virus. | At Day 42 | 
| Anti-rubella Virus Antibody Concentration in Pooled MMR Groups | Antibody concentrations were expressed as GMCs in IU/mL. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any Solicited General AEs | Assessed solicited general AEs were drowsiness, irritability and loss of appetite. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 15-days (Days 0-14) post-vaccination period | 
| Number of Subjects Reporting Any Fever | Any fever = Fever ≥ 38°C. | During the 43-days (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting Any Rash | Assessed were any localized or generalized rash, rash with fever, varicella-like rash, measles/rubella-like rash. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 43-days (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting Any MMR Specific Solicited AEs | Assessed MMR specific solicited AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 43-days (Days 0-42) post-vaccination period | 
| Number of Subjects Reporting Any Unsolicited AEs | Unsolicited adverse event (AE) was defined as any adverse event reported in addition to those solicited during the clinical study and also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 43-days (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. | From Day 0 through the end of study (Day 180) | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity. Any SAE = Occurrence of SAE regardless of intensity grade or relation to vaccination. | From Day 0 through the end of study (Day 180) | 
| Percentage of Subjects With an Anti-HAV Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups | Percentage of subjects with an Anti-HAV antibody concentration equal to or above 15 mIU/mL were reported. | At Day 42 | 
| Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups | Antibody concentrations were expressed as GMCs in mIU/mL. | At Day 42 | 
| Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups | Antibody concentrations were expressed as GMCs in microgram/Milliliter (µg/mL). | At Day 42 | 
| Number of Subjects With Any Solicited Local Adverse Events (AEs) | Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 4-days (Days 0-3) post-vaccination period | 
| Percentage of Subjects With an Anti-Varicella Zoster Virus (VZV) Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups | Seroresponse was defined as post-vaccination anti-VZV antibody concentration ≥75 mIU/mL among subjects who were seronegative (antibody concentration <25 mIU/mL) before vaccination. | At Day 42 | 
| Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups | Antibody concentrations were expressed as GMCs in mIU/mL. | At Day 42 | 

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