Immune Response & Safety of a Hepatitis A Vaccine Given Together With a Pneumococcal Vaccine in Healthy Children 15 m of Age

Hepatitis A Clinical Trial

Official title:

A Phase IIIb, Open, Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine Administered on a 0-6 Mth Schedule Concomitantly With Wyeth Lederle's Pneumococcal Conjugate Vaccine in Healthy Children 15 Months of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00197002
• Other study ID #: 208109/220
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2003
• Est. completion date: January 16, 2006

Study information

• Verified date: June 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to evaluate the immunogenicity and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a pneumococcal conjugate vaccine in children as young as 15 months of age.

Description:

An open, controlled comparison of Havrix administered alone or with Prevnar. The three groups evaluated are: 1) Havrix alone, 2) Havrix plus Prevnar and 3) Prevnar followed by Havrix one month later.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 521
• Est. completion date: January 16, 2006
• Est. primary completion date: January 16, 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 13 Months

Eligibility

Inclusion Criteria:

• A male or female child 12 or 13 months of age at the time of entry into the Enrollment Phase,

• Free of obvious health problems,

• Subjects must have previously received three doses of Prevnar in his/her first year of life.

Exclusion Criteria:

• Use of any investigational or non-registered drug or vaccine within 42 days preceding the first dose of study vaccine, or planned use during the study period,

• Chronic administration 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, less than 0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.),

• Administration of the ACIP-recommended fourth dose of Prevnar prior to entering the Enrollment Phase of the study,

• Planned administration or administration of any vaccine not foreseen by the study protocol within the period of 42 days before and 30 days after each dose of study vaccine(s),

• Previous vaccination against hepatitis A,

• History of hepatitis A or known exposure to hepatitis A,

• 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 Havrix (e.g., neomycin, 2-phenoxyethanol) or Prevnar (e.g., diphtheria toxoid),

• Major congenital defects or serious chronic illness,

• History of any neurologic disorder (history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject),

• Acute disease, defined as the presence of a moderate or severe illness with or without fever, 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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A

Intervention

Biological:
• GSK Biologicals 2-dose inactivated hepatitis A vaccine (Havrix)
Two doses, administered intramuscularly in the right anterolateral thigh.
• Prevnar™
One dose, administered intramuscularly in the left anterolateral thigh.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Bardstown	Kentucky
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Centennial	Colorado
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Kalamazoo	Michigan
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	North Las Vegas	Nevada
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Stony Brook	New York
United States	GSK Investigational Site	University Heights	Ohio
United States	GSK Investigational Site	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (1)

Trofa AF, Levin M, Marchant CD, Hedrick J, Blatter MM. Immunogenicity and safety of an inactivated hepatitis a vaccine administered concomitantly with a pneumococcal conjugate vaccine in healthy children 15 months of age. Pediatr Infect Dis J. 2008 Jul;27(7):658-60. doi: 10.1097/INF.0b013e31816907bd. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Seropositive Subjects for Anti-HAV Antibodies	Cut-off values assessed were greater than or equal to (=) 15 milli-international units per milliliter (mIU/mL) in the sera of subjects seronegative before vaccination.	At one month after Dose 2 of Havrix® vaccine (Month 7-10)
Primary	Concentrations for Anti-HAV Antibodies	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL).	At one month after Dose 2 of Havrix® vaccine (Month 7-10)
Secondary	Anti-4, Anti-6B, Anti-9V, Anti-14, Anti-19F and Anti-23F Antibody Concentrations	Antibody concentrations against pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (µg/mL).	At one month after Prevnar™ vaccination (Day 30)
Secondary	Number of Subjects With an Immune Response to Anti-pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F	The immune response was defined, with respect to anti-pneumococcal response rates, as an antibody concentration equal to or above (=) 0.05 µg/mL.	At one month after Prevnar™ vaccination (Day 30)
Secondary	Number of Seropositive Subjects for Anti-HAV Antibodies	Cut-off values assessed were greater than or equal to (=) 15 mIU/mL in the sera of subjects seronegative before vaccination.	At one month after Dose 1 of Havrix® vaccine (Day 30)
Secondary	Concentrations for Anti-HAV Antibodies	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).	At one month after Dose 1 of Havrix® vaccine (Day 30)
Secondary	Number of Seropositive Subjects for Anti-HAV Antibodies	Cut-off values assessed were greater than or equal to (=) 15 mIU/mL in the sera of subjects seronegative before vaccination.	At one month after Dose 2 of Havrix® vaccine (Month 8-11)
Secondary	Concentrations for Anti-HAV Antibodies	Anti-HAV antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli international units per milliliter (mIU/mL).	At one month after Dose 2 of Havrix® vaccine (Month 8-11)
Secondary	Number of Subjects With Vaccine Response to Anti-HAV Antibodies	The vaccine response was defined as: a detectable anti-HAV antibody concentration one month after Dose 2 in subjects who were initially seronegative (antibody concentrations < 15 mIU/mL for anti-HAV); or; a 2-fold increase above the pre-vaccination concentration one month after Dose 2 in subjects who were initially seropositive (antibody concentrations = 15 mIU/mL for anti-HAV).	One month after Dose 2 of Havrix® vaccine (Month 7-10/8-10)
Secondary	Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.	During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (=) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Grade 3 irritability = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination.	During the 4-day (Day 0-3) follow-up period after each vaccine dose and across doses
Secondary	Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the 31-day (Day 0-30) follow-up period
Secondary	Number of Subjects With Serious Adverse Events (SAEs), New Chronic Illnesses (NCIs) and Medically Significant Events (MSEs)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	During the Active Phase (from Day 0 to Day 30 after final vaccine dose for each subject)
Secondary	Number of Subjects With SAEs, NCIs and MSEs	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. NCIs include autoimmune disorders, asthma, type I diabetes, allergies. MSEs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	During the Extended Safety Follow-up (ESFU) Phase (from Day 30 to 6 months after final vaccine dose)

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