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Study to Evaluate the Immunogenicity and Safety of an Investigational Influenza Vaccine (H1N1) in Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00972517
First received: September 3, 2009
Last updated: September 22, 2016
Last verified: September 2016
  Purpose
The objective of this study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A in children aged between 3 and 17 years.

Condition Intervention Phase
Influenza
Biological: GSK investigational vaccine GSK2340272A
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 3 to 17 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Humoral immune response in terms of Haemagglutination Inhibition (HI) antibody titers against the Flu A/California/7/2009 (H1N1) vaccine strain [ Time Frame: At Day 0, Day 21 and Day 42 ] [ Designated as safety issue: No ]
  • Number of seroconverted subjects for HI antibodies against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.

  • Number of subjects who were seroprotected for HI antibodies against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.

  • HI antibody geometric mean fold rise (GMFR) against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]
    GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years


Secondary Outcome Measures:
  • Humoral immune response in terms of Haemagglutination Inhibition (HI) antibody titers against the Flu A/California/7/2009 (H1N1) vaccine strain [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as geometric mean titers (GMTs)

  • Humoral immune response in terms of Haemagglutination Inhibition (HI) antibody titers against the Flu A/California/7/2009 (H1N1) vaccine strain [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as geometric mean titers (GMTs)

  • Number of seroconverted subjects for HI antibodies against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.

  • Number of subjects who were seroprotected for HI antibodies against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.

  • Number of subjects who were seroprotected for HI antibodies against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.

  • HI antibody geometric mean fold rise (GMFR) against the Flu A/California/7/2009 (H1N1) virus strain [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
    GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years

  • Humoral immune response in terms of neutralising antibodies against the Flu A/Netherlands/602/2009 (H1N1) vaccine strain [ Time Frame: At Day 0, Day 21, Day 42 and Month 6 ] [ Designated as safety issue: No ]
  • Humoral immune response in terms of neutralising antibodies against the Flu A/Netherlands/602/2009 (H1N1) vaccine strain [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). This analysis was conducted on a subset of one third of the subjects who were randomly selected.

  • Number of seroconverted subjects for neutralising antibodies against the Flu A/Netherlands/602/2009 (H1N1) virus strain [ Time Frame: At Day 21 and Day 42 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. This analysis was conducted on a subset of one third of the subjects who were randomly selected.

  • Number of seroconverted subjects for neutralising antibodies against the Flu A/Netherlands/602/2009 (H1N1) virus strain [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years. This analysis was conducted on a subset of one third of the subjects who were randomly selected.

  • Number of subjects reporting Any and Grade 3 solicited local symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities as assessed by inability to attend/do work or school or cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. > 50mm.

  • Number of subjects reporting Any, Grade 3 and Related solicited general symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were arthralgia, diarrhoea, drowsiness, fatigue, gastro-intestinal symptoms, headache, irritability, loss of appetite, myalgia, shivering, sweating and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C.

  • Number of subjects reporting any Medically Attended Adverse Events (MAEs) [ Time Frame: During the entire study period (Day 0 to Month 12) ] [ Designated as safety issue: No ]
    MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination.

  • Number of subjects reporting any Adverse Events of Specific Interest (AESI)/potential immune-mediated diseases (pIMDs) [ Time Frame: During the entire study period (Day 0 to Month 12) ] [ Designated as safety issue: No ]
    Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune etiology. "Any pIMD" was defined as at least one pIMD experienced by the study subject.

  • Number of subjects reporting any, grade 3 and related unsolicited adverse events (AEs). [ Time Frame: Within the 84-day after the first vaccination or from 63-day follow-up period after the second vaccination ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

  • Number of subjects reporting any and related serious adverse events (SAEs) [ Time Frame: During the entire study period (Day 0 to Month 12) ] [ Designated as safety issue: No ]
    A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

  • Number of subjects with normal and abnormal haematological and biochemistry parameters with respect to Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), Total Bilirubin, Bilirubin Conjugated/ Direct,Creatine and Blood urea nitrogen(BUN) [ Time Frame: At Day 0, Day 21, Day 42 and Month 6 (M6) ] [ Designated as safety issue: No ]
    Subjects were categorized by age and according to their results at pre-vaccination (Day 0), Day 21, Day 42 and Month 6 which were below, within and above the normal ranges or unknown


Enrollment: 245
Study Start Date: September 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Subjects receiving alternative dose of GSK23440272A vaccine
Biological: GSK investigational vaccine GSK2340272A
Three intramuscular injections

Detailed Description:
This Protocol Posting has been updated following Protocol amendment 1, October 2009. The impacted section are the study design section, the outcomes measures section and the intervention section.
  Eligibility

Ages Eligible for Study:   3 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
  • Children, male or female, aged between 3 and 17 years at the time of the first study vaccination.
  • Written informed consent obtained from the subject parent(s) or LAR(s) of the subject. Assent obtained from the subject when applicable.
  • Healthy children as established by medical history and clinical examination when entering into the study.
  • Parent/LAR with access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device.

Exclusion Criteria:

  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period.
  • Clinically or virologically confirmed influenza infection within six months preceding the study start.
  • Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration.
  • Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period.
  • Acute disease and/or fever at the time of enrolment
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
  • Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
  • Previous administration of any H1N1 A/California-like vaccine.
  • Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study.
  • If the subject is female and if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.
  • Any known or suspected allergy to any constituent of influenza vaccines; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
  • Known use of an analgesic or antipyretic medication within 12 hours prior to first vaccination.
  • Child in Care.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972517

Locations
Germany
GSK Investigational Site
Kehl, Baden-Wuerttemberg, Germany, 77694
GSK Investigational Site
Pforzheim, Baden-Wuerttemberg, Germany, 75172
GSK Investigational Site
Schwaebisch-Hall, Baden-Wuerttemberg, Germany, 74523
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70469
GSK Investigational Site
Bindlach, Bayern, Germany, 95463
GSK Investigational Site
Cham, Bayern, Germany, 93413
GSK Investigational Site
Muenchen, Bayern, Germany, 81241
GSK Investigational Site
Noerdlingen, Bayern, Germany, 86720
GSK Investigational Site
Frankenthal, Rheinland-Pfalz, Germany, 67227
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Worms, Rheinland-Pfalz, Germany, 67547
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00972517     History of Changes
Other Study ID Numbers: 113638 
Study First Received: September 3, 2009
Last Updated: September 22, 2016
Health Authority: Germany: Paul-Ehrlich-Institut
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
GSK Bio's influenza vaccine GSK2340272A
influenza infection

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 26, 2016