Clinical trial NCT01681992: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Children in Their Second Year of Life
Official title: Immunogenicity and Safety Study of GSK Biologicals' Priorix Vaccine (209762) at an End of Shelf-life Potency Compared to Merck & Co., Inc.'s Measles-mumps-rubella (MMR) Vaccine When Both Are Given on a 2-dose Schedule to Healthy Children in Their 2nd Year of Life
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Measles
Mumps
Rubella
Measles-Mumps-Rubella Vaccine
Keywords: Safety
Measles, mumps and rubella diseases
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-09-10
Enrollment: 4538
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])
timeFrame: At Day 42
measure: Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
timeFrame: At Day 42
measure: Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])
timeFrame: At Day 42
measure: Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
timeFrame: At Day 42
measure: Anti-measles Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 42
measure: Anti-mumps Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 42
measure: Anti-mumps Virus Antibody Concentrations (by PRNT)
timeFrame: At Day 42
measure: Anti-rubella Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 42
Secondary outcomes:
measure: Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
timeFrame: At Day 84
measure: Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
timeFrame: At Day 84
measure: Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
timeFrame: At Day 84
measure: Anti-measles Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 84
measure: Anti-mumps Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 84
measure: Anti-rubella Virus Antibody Concentrations (by ELISA)
timeFrame: At Day 84
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1
timeFrame: During the 4-day (Days 0-3) post-vaccination period
measure: Number of Subjects With Any Solicited Local AEs Post Dose 2
timeFrame: During the 4-day (Days 0-3) post-vaccination period
measure: Number of Subjects With Any Solicited General AEs Post Dose 1
timeFrame: During the 15-day (Days 0-14) post-vaccination period
measure: Number of Subjects Reporting Any Fever Post Dose 1
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any Fever Post Dose 2
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any Rash Post Dose 1
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any Rash Post Dose 2
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any Unsolicited AES Post Dose 1
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any Unsolicited AES Post Dose 2
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Any AEs of Specific Interest
timeFrame: From Day 0 through the end of the study (Day 222)
measure: Number of Subjects Reporting Any Serious Adverse Events (SAEs)
timeFrame: From Day 0 through the end of the study (Day 222)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Jonesboro
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: West Covina
country: United States
facility: GSK Investigational Site
state: California
city: Altamonte Springs
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Naples
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Muncie
country: United States
facility: GSK Investigational Site
state: Indiana
city: New Albany
country: United States
facility: GSK Investigational Site
state: Indiana
city: West Des Moines
country: United States
facility: GSK Investigational Site
state: Iowa
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Annapolis
country: United States
facility: GSK Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Frederick
country: United States
facility: GSK Investigational Site
state: Maryland
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Lincoln
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Clyde
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Toledo
country: United States
facility: GSK Investigational Site
state: Ohio
city: Youngstown
country: United States
facility: GSK Investigational Site
state: Ohio
city: Gresham
country: United States
facility: GSK Investigational Site
state: Oregon
city: Johnstown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Layton
country: United States
facility: GSK Investigational Site
state: Utah
city: Saint George
country: United States
facility: GSK Investigational Site
state: Utah
city: Springville
country: United States
facility: GSK Investigational Site
state: Utah
city: Midlothian
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ellensburg
country: United States
facility: GSK Investigational Site
state: Washington
city: Benesov
country: Czechia
facility: GSK Investigational Site
city: Chlumec nad Cidlinou
country: Czechia
facility: GSK Investigational Site
city: Decin
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Kladno
country: Czechia
facility: GSK Investigational Site
city: Liberec
country: Czechia
facility: GSK Investigational Site
city: Lipnik nad Becvou
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Odolena voda
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Kuala Terengganu
country: Malaysia
facility: GSK Investigational Site
city: Kuching
country: Malaysia
facility: GSK Investigational Site
city: Sibu
country: Malaysia
facility: GSK Investigational Site
city: Guayama
country: Puerto Rico
facility: GSK Investigational Site
city: Ponce
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Centelles (Barcelona)
country: Spain
facility: GSK Investigational Site
city: L'Eliana, Valencia
country: Spain
facility: GSK Investigational Site
city: Manlleu
country: Spain
facility: GSK Investigational Site
city: Quart De Poblet, Valencia
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vic
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiang mai
country: Thailand
facility: GSK Investigational Site
city: Pathum Thani
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: MMR-161 Study Group. Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12-15 months: A phase III, randomized, non-inferiority trial. Vaccine. 2018 Sep 11;36(38):5781-5788. doi: 10.1016/j.vaccine.2018.07.076. Epub 2018 Aug 10.