Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life

Phase 3CompletedNCT01681992

GlaxoSmithKline4,538 enrolled

Overview

The purpose of this study is to evaluate end of shelf-life potency in terms of the immunogenicity and safety of GSK Biologicals' trivalent MMR vaccine, by comparing it to Merck \& Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

This trial is a Phase IIIA, randomized, observer-blind, controlled, multi-center, multi-country study with four parallel groups. This study will evaluate the immunogenicity and safety of GSK Biologicals' trivalent investigational MMR vaccine (referred to as Inv\_MMR vaccine, throughout this document) in contrast 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 first dose of this two-dose study is designed to establish the end of shelf-life potency of Inv\_MMR vaccine. The Inv\_MMR vaccine will be given as one of two lots; one of a minimum potency, designated Inv\_MMR\_Min; and the other at a mid-range or medium potency designated Inv\_MMR\_Med to two groups. The second dose for both of these Inv\_MMR groups will have a potency within the release range of the marketed vaccine. The Com\_MMR vaccine will consist of two lots designated Com\_MMR\_L1 and Com\_MMR\_L2 and will be analyzed as pooled lots within the study. The first MMR vaccine dose will be co-administered with Varivax, Havrix and (in the US sub-cohort only) Prevnar 13 which are routinely administered to children of this age in the US.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

4,538

Conditions

Measles Mumps Rubella Measles-Mumps-Rubella Vaccine

Interventions

PriorixBIOLOGICAL

Subjects receive one dose of either minimum (Inv\_MMR\_Min) or medium (Inv\_MMR\_Med) potency lot at Day 0 and a dose of separate potency lot (Inv\_MMR\_Release) at Day 42, administered subcutaneously in the triceps region of the left arm.

M-M-R IIBIOLOGICAL

Subjects receive two doses of either Lot 1 or Lot 2, one at Day 0 and one at Day 42, administered subcutaneously in the triceps region of the left arm.

VarivaxBIOLOGICAL

Subjects receive one dose co-administered subcutaneously with the study vaccines (Priorix and M-M-R II), in the triceps region of right arm, at Day 0.

Eligibility

Sex: ALLMin age: 12 MonthsMax age: 15 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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 with 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 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. * 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 (or ending at Visit 3 for the US post-dose 2 sub-cohort). Please Note: * Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time during the study, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s). * Any age appropriate vaccine may be given starting at Visit 2 (or starting at Visit 3 for the US post-dose 2 sub-cohort), 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, or at Visit 3 for the US post-dose 2 sub-cohort. * History of measles, mumps, rubella, varicella/zoster and/or hepatitis A diseases. * Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting 30 days prior to the 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. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Fever is defined as temperature ≥38°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 any pneumococcal conjugate vaccine.

Locations (81)

Outcomes

Primary Outcomes

Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])

For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration equal or above \[≥\] 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration less than \[\<\] 150 mIU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for measles virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to measles virus.

Time frame: At Day 42

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

For mumps virus, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 5 EU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for mumps virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to mumps virus.

Time frame: At Day 42

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])

For mumps virus as measured by PRNT, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 4 End point Dilution 50% (ED50) (PRNT) among subjects who were seronegative (antibody concentration \< 2.5 ED50) before dose 1.

Time frame: At Day 42

Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

For rubella virus, a seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 4 IU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv\_MMR\_Min/Inv\_MMR\_Med vaccine in terms of seroresponse rate for rubella virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv\_MMR\_Min/Inv\_MMR\_Med was to be ≥ 90% for antibodies to mumps virus.

Data from ClinicalTrials.gov

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Secondary Outcomes

Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration ≥ 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 150 mIU/mL) before dose 1.

Time frame: At Day 84

Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

Time frame: At Day 84

Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)

Time frame: At Day 84

Anti-measles Virus Antibody Concentrations (by ELISA)

Antibody concentrations were expressed as GMCs in mIU/mL.

Time frame: At Day 84

Anti-mumps Virus Antibody Concentrations (by ELISA)

Antibody concentrations were expressed as GMCs in EU/mL.

Time frame: At Day 84

Anti-rubella Virus Antibody Concentrations (by ELISA)

Antibody concentrations were expressed as GMCs in IU/mL.

Time frame: At Day 84

Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1

Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.

Time frame: During the 4-day (Days 0-3) post-vaccination period

Number of Subjects With Any Solicited Local AEs Post Dose 2

Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.

Time frame: During the 4-day (Days 0-3) post-vaccination period

Number of Subjects With Any Solicited General AEs Post Dose 1

Assessed solicited general AEs were drowsiness, irritability/fussiness and loss of appetite. Any = Occurrence of the AE regardless of intensity grade or relation to vaccination.

Time frame: During the 15-day (Days 0-14) post-vaccination period

Number of Subjects Reporting Any Fever Post Dose 1

Any fever = Fever (axillary) ≥ 38°C.