Clinical trial NCT00197015: Immunogenicity & Safety of Hepatitis A Vaccine Co-admin With a Measles/Mumps/Rubella & a Varicella Vaccine in Children
Official title: Immunogenicity & Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine (Havrix™) Co-administered With Merck & Company, Inc. Measles-Mumps-Rubella Vaccine (M-M-RII) & Merck & Co Varicella Vaccine (VARIVAX™) to Children 15 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis A
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 1474
Sex: ALL
Minimum age (years): 12
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a study to evaluate the immune response and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a measles/mumps/rubella vaccine and a varicella (chickenpox) vaccine in children as young as 15 months of age.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: An open, controlled comparison of Havrix™ administered alone or with MMR II and Varivax™. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + MMR II and Varivax™ and 3) MMR II and Varivax™ followed by Havrix™ one month later.

Eligibility criteria: Inclusion Criteria:

* Subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol
* A male or female child 12 and 13 months of age at the time of entry into the Enrollment Phase
* Written informed consent obtained from the parents or guardian of the subject,
* Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and
* Parents/guardian of the subject must have a telephone or be able to be contacted by telephone

Exclusion Criteria:

* Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 42 days preceding the first dose of study vaccine, or planned use during the study period, Chronic administration (defined as more than 14 days) of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period. (For corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.) Planned administration or administration of any vaccine not foreseen by the study protocol during the period 31 days before and 31 days after each dose of study vaccine(s).
* Previous vaccination against hepatitis A,
* History of hepatitis A,
* Known exposure to hepatitis A,
* Previous vaccination against measles, mumps, rubella and/or varicella,
* History of measles, mumps, rubella and/or varicella,
* Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to the start of the study,
* Planned chronic use of salicylates during the 6-week period following administration of the doses of study vaccine(s),
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection,
* A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection,
* History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of HavrixTM, M-M-RII or VARIVAXTM, including 2-phenoxyethanol, neomycin and gelatin,
* History of anaphylactic or anaphylactoid reactions to egg proteins,
* History of hypersensitivity/allergic reaction to latex. Note: The tip cap and the rubber plunger of the HavrixTM needleless pre-filled syringes contain dry natural latex rubber.
* Major congenital defects or serious chronic illness,
* Active untreated tuberculosis,
* History of significant blood dyscrasias
* History of any neurologic disorder (a history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject)
* Acute disease at the time of vaccination
* Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period

Primary outcomes:
measure: Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups.
timeFrame: 31 days following the second dose of Havrix®
measure: Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups
timeFrame: 31 days following the second dose of Havrix®
measure: Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
timeFrame: 42 days following the administration of M-M-R®II and VARIVAX®
measure: Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
timeFrame: 42 days following administration of M-M-R®II and VARIVAX®
Secondary outcomes:
measure: Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups
timeFrame: 42 days following the administration of M-M-R®II and VARIVAX®
measure: Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups
timeFrame: 42 days following the first dose of Havrix®
measure: Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups
timeFrame: 42 days following the first dose of Havrix®
measure: Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group
timeFrame: 31 days following the second dose of Havrix®
measure: Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group
timeFrame: 31 days following the second dose of Havrix®
measure: Number of Subjects With Vaccine Response to Havrix®
timeFrame: 31 days following the second dose of Havrix®
measure: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: During the 4-day period following each dose of vaccine
measure: Number of Subjects Reporting Solicited General Symptoms
timeFrame: During the 4-day period following each dose of vaccine
measure: Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events
timeFrame: During the 43-day period following each dose of vaccine
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: During the 31-day period following each dose of vaccine
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
measure: Number of Subjects Reporting New Chronic Illnesses
timeFrame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
measure: Number of Subjects Reporting Medically Significant Events
timeFrame: During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end)
Other outcomes:
Locations:
city: Cabot
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Jonesboro
country: United States
facility: GSK Investigational Site
state: Arkansas
city: North Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: Norwich
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Waterloo
country: United States
facility: GSK Investigational Site
state: Iowa
city: Waukee
country: United States
facility: GSK Investigational Site
state: Iowa
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Bossier City
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Brooklyn
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Lumberton
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Sylva
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: University Heights
country: United States
facility: GSK Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Beaver Falls
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Rydal
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sellersville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Warwick
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Bristol
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Temple
country: United States
facility: GSK Investigational Site
state: Texas
city: Layton
country: United States
facility: GSK Investigational Site
state: Utah
city: South Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Marshfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rinderknecht S, Michaels MG, Blatter M, Gaglani M, Andrews W, Abughali N, Chandreshekaran V, Trofa AF. Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with measles-mumps-rubella and varicella vaccines in children less than 2 years of age. Pediatr Infect Dis J. 2011 Oct;30(10):e179-85. doi: 10.1097/INF.0b013e31822256a5.