Study to Determine the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals; Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants

Immunogenicity and Safety Study of GSK Biologicals' Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants

The purpose of this study is to assess the immunogenicity and safety of GSK Biologicals' Infanrix hexa vaccine when administered to healthy infants as primary vaccination at 2, 4 and 6 months of age, co-administered with Prevnar and Rotarix with a booster dose of GSK Biologicals' Infanrix and Hiberix vaccines at 15-18 months of age.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Tetanus; Diphtheria; Acellular Pertussis; Poliomyelitis; Haemophilus Influenzae Type b
• Intervention / Treatment: Biological: Infanrix hexa; Biological: Infanrix; Biological: Hiberix; Biological: Prevnar13; Biological: Rotarix; Biological: Pediarix; Biological: ActHIB; Biological: Pentacel; Biological: Engerix-B

• Study Type: Interventional
• Enrollment (Actual): 585
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • GSK Investigational Site
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • GSK Investigational Site
  • California
    • Anaheim, California, United States, 92804
      • GSK Investigational Site
    • Daly City, California, United States, 94015
      • GSK Investigational Site
    • Fresno, California, United States, 93726
      • GSK Investigational Site
    • Hayward, California, United States, 94545
      • GSK Investigational Site
    • Oakland, California, United States, 94611
      • GSK Investigational Site
    • Pleasanton, California, United States, 94588
      • GSK Investigational Site
    • Roseville, California, United States, 95661
      • GSK Investigational Site
    • Sacramento, California, United States, 95823
      • GSK Investigational Site
    • Sacramento, California, United States, 95815
      • GSK Investigational Site
    • San Jose, California, United States, 95119
      • GSK Investigational Site
    • Santa Clara, California, United States, 95051
      • GSK Investigational Site
    • Walnut Creek, California, United States, 94596
      • GSK Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80922
      • GSK Investigational Site
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • GSK Investigational Site
    • Orange City, Florida, United States, 32763
      • GSK Investigational Site
  • Georgia
    • Marietta, Georgia, United States, 30062
      • GSK Investigational Site
    • Woodstock, Georgia, United States, 30189
      • GSK Investigational Site
  • Idaho
    • Nampa, Idaho, United States, 83686
      • GSK Investigational Site
  • Kansas
    • Augusta, Kansas, United States, 67010
      • GSK Investigational Site
    • Newton, Kansas, United States, 67114
      • GSK Investigational Site
    • Topeka, Kansas, United States, 66604
      • GSK Investigational Site
    • Wichita, Kansas, United States, 67205
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • GSK Investigational Site
    • Louisville, Kentucky, United States, 40291
      • GSK Investigational Site
    • Nicholasville, Kentucky, United States, 40356
      • GSK Investigational Site
  • Maryland
    • Columbia, Maryland, United States, 21045
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • GSK Investigational Site
  • New York
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • Ohio
    • Dayton, Ohio, United States, 45414
      • GSK Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • GSK Investigational Site
    • Sellersville, Pennsylvania, United States, 18960
      • GSK Investigational Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • GSK Investigational Site
  • Utah
    • Layton, Utah, United States, 84041
      • GSK Investigational Site
    • Payson, Utah, United States, 84651
      • GSK Investigational Site
    • Provo, Utah, United States, 84604
      • GSK Investigational Site
    • Saint George, Utah, United States, 84790
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
    • South Jordan, Utah, United States, 84095
      • GSK Investigational Site
    • West Jordan, Utah, United States, 84088
      • GSK Investigational Site
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • GSK Investigational Site
  • Washington
    • Ellensburg, Washington, United States, 98926
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects' parent(s)/ Legally Acceptable Representative(s) (LARs) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
• A male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.
• Born full-term (i.e. after a gestation period of 37 weeks to less than 42 completed weeks [259 to 293 days]).
• Written informed consent obtained from parent(s)/LAR(s) of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrolment.

Exclusion Criteria:

• Child in care
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccines, or planned use during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.

• Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting from 30 days before the first vaccination until 30 days after Dose 3 (Epoch 001, primary vaccination) and from 30 days before the booster Dose 4 until 30 days after booster Dose 4 (Epoch 002, booster vaccination), i.e. the end of the study:

  • Inactivated influenza and hepatitis A vaccines are allowed throughout the study.
  • Routine administration(s) of vaccines are allowed from 30 days after the last dose of primary vaccination until 30 days before the booster dose and after post-booster blood sampling. Routine administration of measles-mumps-rubella vaccine, varicella, pneumococcal vaccines are allowed from 30 days after last dose of primary vaccine until 30 days before booster dose and from post-booster blood sampling, as well as according to the recommended immunization schedule in US.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• History of Hib, diphtheria, tetanus, pertussis, pneumococcal, rotavirus, poliovirus and hepatitis B diseases.
• Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, rotavirus and/or poliovirus; more than one previous dose of hepatitis B vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including yeast).
• Hypersensitivity to latex.
• Major congenital defects or serious chronic illness.
• History of any neurological disorders including seizures.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• History of intussusception or of any uncorrected congenital malformation of the gastrointestinal tract that would predispose the infant to intussusception.
• History of Severe Combined Immunodeficiency Disease (SCID).

• Acute disease and/or fever at the time of enrolment.

  • Fever is defined as temperature ≥38.0°C /100.4°F by any route. The preferred route for recording temperature in this study will be rectal for Epoch 001 and axillary for Epoch 002.
  • Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infanrix hexa Group; Subjects between, and including, 6 and 12 weeks of age at the time of the vaccination received, in the Primary Phase of the study, 3 doses of Infanrix hexa (lot A, lot B or lot C as per the group allocation) co-administered with Prevnar13 at 2, 4 and 6 months of age and Rotarix at 2 and 4 months of age. The injectable vaccines were administered by intramuscular injection in the anterolateral thigh, while Rotarix was administered orally. Subjects received a booster dose of Infanrix and Hiberix at 15-18 months of age by intramuscular injection in the anterolateral thigh.	Biological: Infanrix hexa; 3 doses administered intramuscularly in the right thigh.; Biological: Infanrix; 1 dose administered intramuscularly in the right thigh; Biological: Hiberix; 1 dose administered intramuscularly in the left thigh; Biological: Prevnar13; 3 doses administered intramuscularly in the lower left thigh; Biological: Rotarix; 2 doses administered orally
Active Comparator: Pediarix Group; Subjects between, and including, 6 and 12 weeks of age at the time of the vaccination received, in the Primary Phase of the study, 3 doses of Pediarix and ActHIB co-administered with Prevnar13 at 2, 4 and 6 months of age and Rotarix at 2 and 4 months of age. The injectable vaccines were administered by intramuscular injection in the anterolateral thigh, while Rotarix was administered orally. Subjects received a booster dose of Infanrix and ActHIB at 15-18 months of age by intramuscular injection in the anterolateral thigh.	Biological: Infanrix; 1 dose administered intramuscularly in the right thigh; Biological: Prevnar13; 3 doses administered intramuscularly in the lower left thigh; Biological: Rotarix; 2 doses administered orally; Biological: Pediarix; 3 doses administered intramuscularly in the right thigh; Biological: ActHIB; 4 doses administered intramuscularly in the upper left thigh
Active Comparator: Pentacel Group; Subjects between, and including, 6 and 12 weeks of age at the time of the vaccination received, in the Primary Phase of the study, 3 doses of Pentacel and Engerix co-administered with Prevnar13 at 2, 4 and 6 months of age and Rotarix at 2 and 4 months of age. The injectable vaccines were administered by intramuscular injection in the anterolateral thigh, while Rotarix was administered orally. Subjects received a booster dose of Pentacel at 15-18 months of age by intramuscular injection in the anterolateral thigh.	Biological: Prevnar13; 3 doses administered intramuscularly in the lower left thigh; Biological: Rotarix; 2 doses administered orally; Biological: Pentacel; 4 doses administered intramuscularly in the right thigh; Biological: Engerix-B; 2 or 3 doses administered intramuscularly in the upper left thigh

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Concentrations for Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN).	Concentrations were expressed as geometric mean concentrations (GMCs) for the following cut-offs:2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN. The results for the Infanrix hexa Group and Pediarix Group were the primary outcome variables.	At Month 5, one month after the third dose of the primary vaccination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.	A seropositive subject was defined as a subject with antibody concentrations above to or equal to (≥) 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Month 5, one month after the third dose of the primary vaccination.
Number of Seroprotected Subjects Against Tetanus (T).	A seroprotected subject was defined a a subject with antibody concentrations ≥ 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination.
Number of Seroprotected Subjects Against Diphtheria (D).	A seroprotected subject was defined a a subject with antibody concentrations ≥ 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination.
Antibody Concentrations for Anti-T.	Concentrations were expressed as GMCs for the seroprotection cut-off of 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination
Antibody Concentrations for Anti-D.	Concentrations were expressed as GMCs for the seroprotection cut-off of 0.1 IU/mL.	At Month 5, one month after the third dose of the primary vaccination
Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.	A seroprotected subject was defined as a subject with anti-polio types 1, 2 and 3 titres ≥ 8 dilution.	At Month 5, one month after the third dose of the primary vaccination
Antibody Titres for Anti-polio Types 1, 2 and 3.	Titres were expressed as geometric mean titres (GMTs) for the cut-off of 8 dilution.	At Month 5, one month after the third dose of the primary vaccination
Number of Seroprotected Subjects Against Polyribosyl Ribitol Phosphate (Anti-PRP).	A seroprotected subject was defined as a subject with anti-PRP concentrations ≥ 0.15 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 1 µg/mL.	The cut-off for this assay was an anti-PRP concentration ≥ 1 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Antibody Concentrations for Anti-PRP.	Antibody concentrations were expressed as GMCs for the assay cut-off of 1 µg/mL.	At Month 5, one month after the third dose of the primary vaccination
Number of Seroprotected Subjects Against Hepatitis B (Anti-HBs).	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mili-International units per mililiter (mIU/mL).	At Month 5, one month after the third dose of the primary vaccination
Antibody Concentrations for Anti-HBs.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 10 mIU/mL.	At Month 5, one month after the third dose of the primary vaccination
Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (≥); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following Dose 1
Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness (Red) and swelling (Swe). Any = any reports of the specific symptom irrespective of intensity grade; above or equal (≥); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following Dose 2
Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (≥); Grade 2 Redness/Swelling: > 5 millimeters (mm); Grade 3 Redness (Red)/Swelling (Swe): > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA	During the 4-day (Days 0-3) post-vaccination period following Dose 3
Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (≥); Grade 2 Redness (Red)/Swelling (Swe): > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-vaccination period following any dose.
Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature ≥ 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 1.
Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature ≥ 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 2.
Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature ≥ 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Feve:r > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following Dose 3.
Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature ≥ 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-vaccination period following any dose.
Number of Subjects With Specific Adverse Events (AEs).	Occurrence of specific adverse events, i.e., new onset chronic diseases (e.g. autoimmune disorders, asthma, type I diabetes and allergies)	From Month 0 up to 6 months post primary-vaccination (Month 10)
Number of Subjects With Unsolicited AEs.	An unsolicited AE is 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.	During the 31-day (Days 0-30) post-primary vaccination period.
Number of Subjects With Serious Adverse Events (SAEs).	SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.	From Month 0 up to 6 months post-primary vaccination (Month 10)
Number of Seroprotected Subjects Against Anti-T.	A seroprotected subject was defined a subject with antibody concentrations ≥ 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 (At Month 14-17 one month after the booster dose (Dose 4)]
Number of Seroprotected Subjects Against Anti-D.	A seroprotected subject was defined a subject with antibody concentrations ≥ 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 (At Month 14-17 one month after the booster dose (Dose 4)]
Antibody Concentrations for Anti-T.	Concentrations were expressed as GMCs for the seropositivity cut-off of 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Antibody Concentrations for Anti-D.	Concentrations were expressed as GMCs for the seropositivity cut-off of 0.1 IU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.	A seropositive subject was defined as a subject with antibody concentrations above to or equal to (≥) 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 5 [Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [Month 14-17 one month after the booster dose (Dose 4)]
Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN.	Concentrations were expressed as geometric mean concentrations (GMCs) for the following cut-offs:2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 5 [Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [Month 14-17 one month after the booster dose (Dose 4)]
Number of Subjects With a Booster Response for Anti-PT, Anti-FHA and Anti-PRN.	Booster response to PT, FHA and PRN antigens was defined as: For subjects with pre-vaccination antibody concentration below the assay cut off, post-vaccination antibody concentration equal or above 4 times the assay cut-off.; For subjects with pre-vaccination antibody concentration between the assay cut off and below 4 times the assay cut-off, post-vaccination antibody concentration equal or above 4 times the pre-vaccination antibody concentration.; For subjects with pre-vaccination antibody concentration equal or above 4 times the assay cut-off, post-vaccination antibody concentration of at least two times the pre-vaccination antibody concentration. The assay cut off is 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, and 2.187 IU/mL for anti-PRN.	At Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Number of Seroprotected Subjects Against Anti-PRP.	A seroprotected subject was defined as a subject with anti-PRP concentrations ≥ 0.15 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose4)]
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 1 µg/mL.	The cut-off for this assay was an anti-PRP concentration ≥ 1 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose4)]
Antibody Concentrations for Anti-PRP.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 1 µg/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)] and at Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.	A seroprotected subject was defined as a subject with anti-polio types 1, 2 and 3 titres ≥ 8 dilution.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Antibody Titres for Anti-polio Types 1, 2 and 3.	Titres were expressed as geometric mean titres (GMTs) for the cut-off of 8 dilution.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Number of Seroprotected Subjects Against Anti-HBs.	A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Antibody Concentrations for Anti-HBs.	Antibody concentrations were expressed as GMCs for the seroprotection cut-off of 10 mIU/mL.	At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
Number of Subjects With Solicited Local Symptoms.	The solicited local symptoms assessed were pain, redness and swelling. Any = any reports of the specific symptom irrespective of intensity grade; above or equal (≥); Grade 2 Redness (Red)/Swelling (Swe): > 5 millimeters (mm); Grade 3 Redness/Swelling: > 20 mm; Grade 2 Pain = Moderate: cries/protests on touch; Grade 3 Pain = Severe: Cries when limb is moved/spontaneously painful. Grade = G; Medical Advice = MA.	During the 4-day (Days 0-3) post-booster vaccination.
Number of Subjects With Solicited General Symptoms.	The solicited general symptoms assessed were Drowsiness, Irritability/Fussiness, Loss Of Appetite and Fever (defined as temperature ≥ 38.0°C). Any = any reports of the specific symptom irrespective of intensity grade; Grade 2 (G2) Drowsiness = Drowsiness that interfered with normal activity; Grade 2 Irritability/Fussiness = Moderate: Cried more than usual/interfered with normal activity; Grade 2 Loss of appetite = Ate less than usual/interfered with normal activity; Grade 2 Fever: > 39.0 °C and ≤ 40.0 °C; Grade 3 (G3) Drowsiness/Irritability/Fussiness = symptom that prevented normal activity; Grade 3 Loss of appetite = Did not eat at all; Grade 3 Fever: > 40.0 °C; Related (Rel) = Symptom which was assessed by the investigator as related to vaccination.	During the 4-day (Days 0-3) post-booster vaccination.
Number of Subjects With Specific AEs.	Occurrence of specific adverse events, i.e., new onset chronic diseases (e.g. autoimmune disorders, asthma, type I diabetes and allergies)	During the 31-day (Days 0-30) post-booster vaccination.
Number of Subjects With Unsolicited AEs.	An unsolicited AE is 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.	During the 31-day (Days 0-30) post-booster vaccination.
Number of Subjects With SAEs.	SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.	During the 31-day (Days 0-30) post-booster vaccination.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Klein NP, Abu-Elyazeed R, Cheuvart B, Janssens W, Mesaros N. Immunogenicity and safety following primary and booster vaccination with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine: a randomized trial in the United States. Hum Vaccin Immunother. 2019;15(4):809-821. doi: 10.1080/21645515.2018.1549449. Epub 2019 Jan 4.

Helpful Links

• Full CSR redacted with additional report posting on GSK.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2014
• Primary Completion (Actual): February 6, 2015
• Study Completion (Actual): November 13, 2015

Study Registration Dates

• First Submitted: March 21, 2014
• First Submitted That Met QC Criteria: March 21, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Healthy; Immunogenicity; Infants; Infanrix Hexa
• Additional Relevant MeSH Terms: Digestive System Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Neuromuscular Diseases; Central Nervous System Infections; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Corynebacterium Infections; Hepatitis; Myelitis; Hepatitis B; Diphtheria; Poliomyelitis; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 117119; 2013-004304-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)