Clinical trial NCT01621802: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Combined Measles-mumps-rubella (MMR) Vaccine in Subjects Four to Six Years of Age
Official title: Immunogenicity and Safety Study of GSK Biologicals' Combined Measles-mumps-rubella Vaccine in Subjects Four to Six Years of Age (209762)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Measles-Mumps-Rubella
Keywords: Safety
Measles, mumps and rubella diseases
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-06-18
Enrollment: 4011
Sex: ALL
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to support licensure of GSK Biologicals' MMR vaccine (Priorix®) in the US by generating immunogenicity and safety data in contrast to the US standard of care, Merck's MMR vaccine (M-M-R®II), when given as a second dose to children four to six years of age.

Detailed description: The GSK Biologicals' MMR vaccine (Priorix®) and Merck's MMR vaccine (M-M-R®II) are referred to as Inv_MMR vaccine and Com_MMR vaccine respectively. 2 lots of the comparator vaccine (Com_MMR_L1 and Com_MMR_L2) will be used, but the 2 lots will be analysed as a pool.

The Inv_MMR vaccine will be administered as a second dose to children who already received a first dose Com_MMR vaccine. Since the second dose of a MMR vaccine in the US is routinely co-administered with DTaP-IPV vaccine (Kinrix®) and varicella vaccine (VV) (ProQuad® or Varivax®), some children will receive one dose of these vaccines along with either of the MMR vaccines.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they and/or their parent(s) or LAR/s can and will comply with the requirements of the protocol.
* Male or female subjects 4 to 6 years of age at the time of vaccination.
* Written informed consent is obtained from the parent(s)/LAR(s) of the subject (assent will be obtained from subjects in line with local rules and regulations).
* Subjects in stable health as determined by investigator's physical examination and assessment of subjects' medical history.
* Subjects received either a single dose of M-M-R II, M-M-R VaxPro or ProQuad in the second year of life.
* For subjects enrolled in the sub-cohort receiving co-administered DTaP-IPV and VV:

  * subjects received previous DTaP vaccine doses with INFANRIX® and/or PEDIARIX® for the first three doses and INFANRIX® for the fourth dose of the DTaP-containing vaccine.
  * subjects received a first dose of VV in the second year of life.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the day of study vaccination/s or planned during the entire study period.
* Previous vaccination with a second dose of measles, mumps, rubella containing vaccine/s.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to Day 0 or any planned administration of immunosuppressive and 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 before entering the study or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2.
* Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to the study vaccination/s and ending 42 days after the vaccination/s (at Visit 2), with the exception of live intranasal or inactivated influenza (flu) vaccine, which may be given at any time during the study, including the day of study vaccination/s. Inactivated influenza vaccine must be administered at a different location from the study vaccine. Any age appropriate vaccine may be given starting at Visit 2, and anytime thereafter.
* 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, and/or rubella disease.
* Known exposure to measles, mumps and/or rubella during the period starting 30 days prior to enrollment.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including systemic hypersensitivity to neomycin 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) measured 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 according to the subject's medical history.
* Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

In addition, for subjects enrolled in the sub-cohort receiving co-administered DTaP-IPV+VV:

* Previous vaccination with a second dose of varicella-containing vaccine.
* Receipt of any varicella-containing vaccine during the period starting 90 days before the day of study vaccination.
* History of varicella/zoster disease.
* Known exposure to varicella/zoster during the period starting 30 days prior to enrollment.
* History of diphtheria, tetanus, pertussis, and/or poliomyelitis disease.
* Vaccination against diphtheria, tetanus, pertussis or polio given after the second year of life.
* Occurrence of transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus toxoids.
* Following a previous administration of DTP vaccine: temperature ≥40.6°C (\>105°F) during the period starting 48 hours not due to another identifiable cause, collapse or shock-like state during the period starting 48 hours, persistent, inconsolable crying lasting three hours or more within 48 hours, seizures with or without fever occurring during the period starting three days, or encephalopathy of unknown aetiology occurring during the period starting 7 days of a previous administration of DTP vaccine.
* Hypersensitivity reaction to any component of the DTaP-IPV and/or varicella vaccines.

Primary outcomes:
measure: Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-measles Virus Antibody Concentrations
timeFrame: 42 days after vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-mumps Virus Antibody Concentrations
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-rubella Virus Antibody Concentrations
timeFrame: 42 days post vaccination (At Day 42)
Secondary outcomes:
measure: Number of Subjects With Anti-varicella Zoster Virus (VZV) Antibody Concentration Equal to or Above the Cut-off-value
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-VZV Antibody Concentrations
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Antibody Booster Response to Diphtheria Toxin (Anti-D) and Tetanus Toxin (Anti-T)
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Antibody Booster Response to Pertussis Toxin (PT)
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Antibody Booster Response to Filamentous Hemagglutinin (FHA)
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Antibody Booster Response to Pertactin (PRN)
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 1.0 IU/mL
timeFrame: 42 days post vaccination (At Day 42)
measure: Evaluation of Immunogenicity in Terms of Anti-polio Virus Types 1, 2 and 3 Antibody Titers
timeFrame: 42 days post vaccination (At Day 42)
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 4-day (Days 0-3) post-vaccination period
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 4-day (Days 0-3) post-vaccination period
measure: Number of Subjects Reporting Fever
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting MMR Specific Solicited General Symptoms
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects Reporting Investigator-confirmed Rash
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects With New Onset Chronic Diseases (NOCDs)
timeFrame: During the entire study period (from Day 0 up to Day 180)
measure: Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits
timeFrame: During the entire study period (from Day 0 up to Day 180)
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 43-day (Days 0-42) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 up to Day 180)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Benton
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Fayetteville
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Baldwin Park
country: United States
facility: GSK Investigational Site
state: California
city: Daly City
country: United States
facility: GSK Investigational Site
state: California
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Hayward
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Pleasanton
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Santa Clara
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Altamonte Springs
country: United States
facility: GSK Investigational Site
state: Florida
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Woodstock
country: United States
facility: GSK Investigational Site
state: Georgia
city: Nampa
country: United States
facility: GSK Investigational Site
state: Idaho
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Augusta
country: United States
facility: GSK Investigational Site
state: Kansas
city: Newton
country: United States
facility: GSK Investigational Site
state: Kansas
city: Bardstown
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Columbia
country: United States
facility: GSK Investigational Site
state: Maryland
city: Fall River
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Asheboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
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: Gresham
country: United States
facility: GSK Investigational Site
state: Oregon
city: Erie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Cheraw
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rapid City
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Tomball
country: United States
facility: GSK Investigational Site
state: Texas
city: Provo
country: United States
facility: GSK Investigational Site
state: Utah
city: Saint George
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: South Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Burke
country: United States
facility: GSK Investigational Site
state: Virginia
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Huntington
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Monroe
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Ansan
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: GyeongSangNam-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Iksan
country: Korea, Republic of
facility: GSK Investigational Site
city: Jeollabukdo
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Wonju-si Kangwon-do
country: Korea, Republic of
facility: GSK Investigational Site
city: New Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: MMR-158 Study Group. A second dose of a measles-mumps-rubella vaccine administered to healthy four-to-six-year-old children: a phase III, observer-blind, randomized, safety and immunogenicity study comparing GSK MMR and MMR II with and without DTaP-IPV and varicella vaccines co-administration. Hum Vaccin Immunother. 2019;15(4):786-799. doi: 10.1080/21645515.2018.1554971. Epub 2019 Feb 20.