A Study to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine in Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01218308
First received: October 7, 2010
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

This study is designed to test the efficacy of an investigational influenza vaccine, in children compared to Havrix®, a licensed Hepatitis A virus vaccine.

This study will also evaluate the immunogenicity and safety of the investigational vaccine.


Condition Intervention Phase
Seasonal Influenza
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
Biological: Havrix™
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Efficacy Study of GSK Biologicals' Quadrivalent Influenza Vaccine, GSK2282512A, (FLU Q-QIV) When Administered in Children

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting at Least One Confirmed Occurrence of Influenza A or B. [ Time Frame: From Day 14 to Day 180 ] [ Designated as safety issue: No ]
    To confirm influenza A and/or B disease, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.


Secondary Outcome Measures:
  • Number of Subjects Reporting at Least One Moderate to Severe Occurrence of Influenza A or B. [ Time Frame: From Day 14 to Day 180 ] [ Designated as safety issue: No ]

    To confirm influenza A and/or B disease moderate to severe cases, a positive RT-PCR result for influenza A or B virus from a nose and throat swab obtained concurrently with an ILI was required. Moderate to severe influenza was defined as RT-PCR-confirmed ILI with:

    • Fever >39°C, and/or at least one of the following manifestations,
    • Physician-verified shortness of breath, pulmonary congestion, pneumonia, bronchiolitis, bronchitis, wheezing, croup, or acute otitis media, and/or one of the following,
    • Physician-diagnosed serious extra-pulmonary complication of influenza, including myositis, encephalitis, seizure, or myocarditis

  • Number of Subjects Reporting at Least One Culture Confirmed Occurrence of Influenza A or B Due to Antigenically Matched Strain. [ Time Frame: From Day 14 to Day 180 ] [ Designated as safety issue: No ]
    To confirm influenza A and/or B disease due to antigenically matched strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.

  • Number of Subjects Reporting at Least One Culture Confirmed Occurrence of Influenza A or B Due to Any Strain. [ Time Frame: From Day 14 to Day 180 ] [ Designated as safety issue: No ]
    To confirm influenza A and/or B disease due to any strain, a positive reverse transcriptase polymerase chain reaction (RT-PCR) result for influenza A or B virus from a nose and throat swab obtained concurrently with an influenza like illness (ILI) was required. ILI was defined as the presence of an oral or axillary temperature ≥ 37.8 degrees Celsius (°C) in the presence of at least one of the following symptoms on the same day: cough, sore throat, runny nose or nasal congestion.

  • Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). The reference cut-off value was the seropositivity cut-off of 1:10. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

  • Number of Seroconverted Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination titer. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

  • Number of Seroprotected Subjects Against 4 Strains of Influenza Disease. [ Time Frame: At Day 0 [PRE] and 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

  • Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At 28 days post vaccination (Day 28 for primed subjects and day 56 for unprimed subjects) [POST] ] [ Designated as safety issue: No ]
    The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 4 influenza strains assessed were the Flu A/California/7/09 (H1N1), Flu A/Victoria/210/09 (H3N2), FluB/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).

  • Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling at the injection site. Any = Incidence of a particular symptom regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful for subjects < 5 years of age or significant pain at rest that prevented normal, everyday activities for subjects ≥ 5 years of age. Grade 3 redness/swelling = Redness/swelling above 100 millimeters (mm) of the injection site. All solicited local symptoms were considered related to vaccination.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects Below 5 Years of Age. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade and relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = not eating at all. Related = General symptom assessed by the investigator as causally related to the study vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Subjects of 5 Years of Age and Above. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (Gastro.), headache, joint pain at other location (Joint pain), muscle aches, shivering and temperature. Any = Occurrence of any solicited general symptom regardless of intensity grade or relation to vaccination. Any temperature = Axillary temperature ≥ 38.0 °C. Grade 3 symptom = Symptom that prevented normal activity. Related = Symptom assessed by the investigator as causally related to the vaccination. Grade 3 temperature = Axillary temperature ≥ 39.0°C.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: During the 28-day (Days 0-27) follow-up period after vaccination ] [ 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. Any = Any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3 = Unsolicited AE that prevented normal activity. Related = Unsolicited AE assessed by the investigator as causally related to the vaccination.

  • Number of Subjects With Any and Related Medically Attended Adverse Events (MAEs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    MAEs were defined as AEs that resulted in medical attention (defined as hospitalization, an emergency room visit or a visit to or from medical personnel for any reason). Any = Any MAE regardless of intensity or relationship to vaccination. Related = MAE assessed by the investigator as causally related to the vaccination.

  • Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    pIMDs were defined as a subset of AEs that included both clearly autoimmune diseases (AID) and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any = Any pIMD(s) regardless of intensity or relationship to vaccination. Related = pIMDs assessed by the investigator as causally related to the vaccination.

  • Number of Subjects With Any and Related Serious Adverse Events (SAEs). [ Time Frame: During the entire study period (Day 0 - Day 180) ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Any = Any SAE(s) regardless of intensity or relationship to vaccination. Related = SAEs assessed by the investigator as causally related to the vaccination.


Enrollment: 5168
Study Start Date: December 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2282512A Group
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of GSK2282512A vaccine at Day 0 and, if unprimed, 2 doses of GSK2282512A vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Biological: Quadrivalent seasonal influenza vaccine GSK2282512A
One intramuscular dose for primed subjects. Two intramuscular doses for unprimed subjects.
Active Comparator: Havrix Group
Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of Havrix™ vaccine at Day 0 and, if unprimed, 2 doses of Havrix™ vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
Biological: Havrix™
Two intramuscular doses for primed subjects. Three intramuscular doses for unprimed subjects.

  Eligibility

Ages Eligible for Study:   3 Years to 8 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they and/or their parent(s) or legally acceptable representative(s) can and will comply with the requirements of the protocol.
  • A male or female child aged between 3 and 8 years inclusive at the time of the first vaccination; children are eligible regardless of history of administration of influenza vaccine in a previous season. However, subjects who have received any seasonal or pandemic influenza vaccine within 6 months preceding the first dose of study vaccine will not be enrolled.
  • Written informed consent obtained from the subject/from the parent(s)/legally acceptable representative(s) of the subject.
  • Written assent obtained from the subject if/as required by local regulations.
  • Subjects in stable health as determined by investigator's clinical examination and assessment of subjects' medical history.
  • Access to a consistent means of telephone contact

Exclusion Criteria:

  • Child in care.
  • Use of an investigational or non-registered product other than the study vaccines within 30 days before study vaccination or planned use during study period. Routine registered childhood vaccinations are permitted.
  • Prior receipt of any seasonal or pandemic influenza vaccine within 6 months preceding the first dose of study vaccine, or planned use of such vaccines during the study period. Prior receipt of more than one dose of a licensed hepatitis A vaccine, with the first dose administered at >=12 months of age.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
  • History of Guillain-Barre syndrome within 6 weeks of receipt of prior influenza virus vaccine.
  • Any known or suspected allergy to any constituent of influenza vaccines ; a history of anaphylactic-type reaction to constituent of vaccine; or a history of severe adverse reaction to a previous influenza vaccine.
  • Fever at the time of enrolment.
  • Acute disease at the time of enrolment.
  • Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Ongoing aspirin therapy.
  • Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01218308

Locations
Bangladesh
GSK Investigational Site
Dhaka, Bangladesh, 1000
Thailand
GSK Investigational Site
Bangkok, Thailand, 10400
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):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01218308     History of Changes
Other Study ID Numbers: 114541
Study First Received: October 7, 2010
Results First Received: February 21, 2013
Last Updated: April 17, 2013
Health Authority: Philippines: Philippines Food and Drug Administration
Lebanon: Republic of Lebanon, Ministry of Health
Turkey: Ministry of Health of Turkey, General Directorate of Pharmaceuticals and Pharmacy
Honduras: Secretaria de Salud de Honduras
United States: Food and Drug Administration
Panama: Departamento de Farmacia y Drogas, Ministerio de Salud de Panama
Dominican Republic: Ministerio de Salud Publica de Republica Dominicana/Direccion general de Drogas y Farmacia, Ministerio de Garantia de Calidad
Thailand: Ministry of Public Health
Bangladesh: Drug Administration Authority, Bangladesh
India: Drugs Controller General of India (DCGI)

Keywords provided by GlaxoSmithKline:
Influenza

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 16, 2014