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

• ClinicalTrials.gov Identifier: NCT01218308
• Recruitment Status: Completed
• First Posted: October 11, 2010
• Results First Posted: April 2, 2013
• Last Update Posted: August 1, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: October 7, 2010
• First Posted Date: October 11, 2010
• Results First Submitted Date: February 21, 2013
• Results First Posted Date: April 2, 2013
• Last Update Posted Date: August 1, 2018
• Study Start Date: December 9, 2010
• Actual Primary Completion Date: January 9, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2013)

Number of Subjects Reporting at Least One Confirmed Occurrence of Influenza A or B. [ Time Frame: From Day 14 to Day 180 ]

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.

• Original Primary Outcome Measures (submitted: October 7, 2010): Occurrence of Reverse-Transcribed Polymerase Chain Reaction- confirmed influenza A and/or B disease [ Time Frame: Approximately 6 months after the vaccination. ]

Current Secondary Outcome Measures (submitted: April 6, 2015)

• Number of Subjects Reporting at Least One Moderate to Severe Occurrence of Influenza A or B. [ Time Frame: From Day 14 to Day 180 ]
  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 ]
  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 ]
  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] ]
  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] ]
  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] ]
  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] ]
  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).
• Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Strains [ Time Frame: On Day 0 and at least 6 months after first vaccination (Month 6) ]
  HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/California/7/2009 (H1N1), Flu A/Victoria/210/09 (H3N2), Flu B/Brisbane/60/08 (Victoria) and Flu B/Florida/4/06 (Yamagata).
• Number of Seroconverted Subjects for HI Antibody Titers Against Each of the 4 Vaccine Influenza Strains. [ Time Frame: At least 6 months after first vaccination (Month 6) ]
  A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were 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 for HI Antibody Titers Against Each of the 4 Vaccine Influenza Strains. [ Time Frame: At Day 0 and at least 6 months after first vaccination (Month 6) ]
  A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were 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 Factors for HI Antibodies Against 4 Strains of Influenza Disease. [ Time Frame: At least 6 months after first vaccination (Month 6) ]
  Seroconversion factors were defined as the fold increase in serum HI 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 ]
  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 ]
  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 ]
  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 ]
  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) ]
  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) ]
  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) ]
  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.

Original Secondary Outcome Measures (submitted: October 7, 2010)

• Occurrence of Reverse-Transcribed Polymerase Chain Reaction- confirmed influenza A and/or B disease associated with a virus isolate phylogenetically-related to one of those included in the vaccine [ Time Frame: Approximately 6 months after the vaccination. ]
• Moderate to severe influenza defined by Reverse-Transcribed Polymerase Chain Reaction-confirmed influenza like illness [ Time Frame: Approximately 6 months after the vaccination ]
• Serum hemagglutination inhibition antibody titer against each of the four vaccine influenza strains (in a subset of subject) [ Time Frame: Day 0, Day 28(primed subjects), Day 56(unprimed subjects) and at the visit of extended safety follow-up (approximately Day 180) ]
• Occurrence, intensity, and relationship to vaccination of solicited local and general adverse events [ Time Frame: During a 7-day follow-up period after each vaccination (Day 0-6) ]
• Occurrence, intensity and relationship to vaccination of unsolicited adverse events [ Time Frame: During a 28-day follow-up period after each vaccination (Day 0-27) ]
• Occurrence and relationship to vaccination of medically attended adverse events, serious adverse events and potential immune-mediated diseases [ Time Frame: During the entire study (from Day 0 to approximately 6 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy of GSK Biologicals' Influenza Vaccine in Children
• Official Title: Efficacy Study of GSK Biologicals' Quadrivalent Influenza Vaccine, GSK2282512A, (FLU Q-QIV) When Administered in Children

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Influenza

Intervention

• Biological: FluLaval® Quadrivalent
  One intramuscular dose for primed subjects. Two intramuscular doses for unprimed subjects.
  Other Name: Quadrivalent seasonal influenza vaccine GSK2282512A
• Biological: Havrix™
  Two intramuscular doses for primed subjects. Three intramuscular doses for unprimed subjects.

Study Arms

• Experimental: FluLaval® Quadrivalent Group
  Subjects between 3 and 8 years of age at the time of first vaccination received, if primed, 1 dose of FluLaval® Quadrivalent vaccine at Day 0 and, if unprimed, 2 doses of FluLaval® Quadrivalent vaccine at Days 0 and 28. The vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm.
  Intervention: Biological: FluLaval® Quadrivalent
• 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.
  Intervention: Biological: Havrix™

• Publications *: Jain VK, Rivera L, Zaman K, Espos RA Jr, Sirivichayakul C, Quiambao BP, Rivera-Medina DM, Kerdpanich P, Ceyhan M, Dinleyici EC, Cravioto A, Yunus M, Chanthavanich P, Limkittikul K, Kurugol Z, Alhan E, Caplanusi A, Durviaux S, Boutet P, Ofori-Anyinam O, Chandrasekaran V, Dbaibo G, Innis BL. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2015): 5220
• Original Estimated Enrollment (submitted: October 7, 2010): 5200
• Actual Study Completion Date: January 9, 2012
• Actual Primary Completion Date: January 9, 2012 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 8 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bangladesh, Dominican Republic, Honduras, Lebanon, Panama, Philippines, Thailand, Turkey

Administrative Information

• NCT Number: NCT01218308
• Other Study ID Numbers: 114541
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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.

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: August 2016