Immunogenicity & Safety of Hepatitis A Vaccine Co-admin With a Measles/Mumps/Rubella & a Varicella Vaccine in Children - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00197015

Purpose

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.

Condition	Intervention	Phase
Hepatitis A Vaccine Hepatitis A	Biological: Havrix® Biological: M-M-R®II Biological: VARIVAX®	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
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 m of Age

Resource links provided by NLM:

MedlinePlus related topics: Chickenpox Hepatitis Hepatitis A Measles Mumps Rubella Shingles

Drug Information available for: Hepatitis A Vaccines Chickenpox Vaccine

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups. [ Time Frame: 31 days following the second dose of Havrix® ] [ Designated as safety issue: No ]
Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL).
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 [ Time Frame: 31 days following the second dose of Havrix® ] [ Designated as safety issue: No ]
Anti-HAV antibody cut-off value assessed include 15 milli-international units per milliliter (mIU/mL).
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups [ Time Frame: 42 days following the administration of M-M-R®II and VARIVAX® ] [ Designated as safety issue: No ]
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 150 milli-international units per milliliter (mIU/mL) for anti-measles antibodies, 28 Effective Dose 50 (ED50) for anti-mumps antibodies and 1:5 for anti-varicella antibodies.
Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups [ Time Frame: 42 days following administration of M-M-R®II and VARIVAX® ] [ Designated as safety issue: No ]
Vaccine response is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off value assessed include 10 milli-international units per milliliter (mIU/mL).

Secondary Outcome Measures:

Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups [ Time Frame: 42 days following the administration of M-M-R®II and VARIVAX® ] [ Designated as safety issue: No ]
Titers are given as geometric mean titers (GMTs).
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups [ Time Frame: 42 days following the first dose of Havrix® ] [ Designated as safety issue: No ]
Concentrations are given as geometric mean concentrations (GMCs).
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 [ Time Frame: 42 days following the first dose of Havrix® ] [ Designated as safety issue: No ]
Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).
Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group [ Time Frame: 31 days following the second dose of Havrix® ] [ Designated as safety issue: No ]
Concentrations are given as geometric mean concentrations (GMCs).
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group [ Time Frame: 31 days following the second dose of Havrix® ] [ Designated as safety issue: No ]
Anti-HAV antibody cut-off value assessed include 15 milli-international units per millilitre (mIU/mL).
Number of Subjects With Vaccine Response to Havrix® [ Time Frame: 31 days following the second dose of Havrix® ] [ Designated as safety issue: No ]
Vaccine response was defined as: 1) a detectable anti-hepatitis A virus (HAV) antibody concentration 31 days following the second dose in subjects who were initially seronegative; and 2) a 2-fold increase in anti-HAV antibody concentrations above the pre-study concentration 31 days following the second dose in subjects who were initially seropositive.
Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 4-day period following each dose of vaccine ] [ Designated as safety issue: No ]
Solicited local symptoms assessed include pain, rash (local), redness and swelling.
Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 4-day period following each dose of vaccine ] [ Designated as safety issue: No ]
Solicited general symptoms assessed include drowsiness, fever, irritability, loss of appetite and rash (general).
Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events [ Time Frame: During the 43-day period following each dose of vaccine ] [ Designated as safety issue: No ]
Specific adverse events assessed include papules, vesicles, crusts, parotid/salivary gland swelling and suspected signs of meningitis/febrile seizures.
Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: During the 31-day period following each dose of vaccine ] [ Designated as safety issue: No ]
Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms
Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: 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) ] [ Designated as safety issue: No ]
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects Reporting New Chronic Illnesses [ Time Frame: 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) ] [ Designated as safety issue: No ]
New Chronic illnesses include autoimmune disorders, asthma, type I diabetes, allergies.
Number of Subjects Reporting Medically Significant Events [ Time Frame: 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) ] [ Designated as safety issue: No ]
Medically significant events include, but are not limited to, diabetes, autoimmune disease, asthma, allergies and/or conditions prompting emergency room or physician office visits that are not related to well-child care, vaccination or common acute illnesses (e.g., upper respiratory infection, otitis media, pharyngitis, gastroenteritis, injury and visits for routine physical examination).

Enrollment:	1474
Study Start Date:	October 2003
Study Completion Date:	June 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: HAV Group Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)	Biological: Havrix® 2 doses administered intramuscularly
Experimental: HAV+MMR+V Group Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9	Biological: Havrix® 2 doses administered intramuscularly Biological: M-M-R®II 1 dose administered subcutaneously Biological: VARIVAX® 1 dose administered subcutaneously
Active Comparator: MMR+V→HAV Group Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)	Biological: Havrix® 2 doses administered intramuscularly Biological: M-M-R®II 1 dose administered subcutaneously Biological: VARIVAX® 1 dose administered subcutaneously

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

Ages Eligible for Study:	12 Months to 13 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00197015

Show 38 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00197015 History of Changes
Other Study ID Numbers:	208109/231
Study First Received:	September 13, 2005
Results First Received:	March 11, 2010
Last Updated:	January 5, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Chickenpox
Hepatitis
Hepatitis A
Measles
Rubella
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Liver Diseases
Digestive System Diseases

Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Morbillivirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
Rubivirus Infections
Togaviridae Infections

ClinicalTrials.gov processed this record on February 12, 2012