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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02853929
Registration number
NCT02853929
Ethics application status
Date submitted
14/07/2016
Date registered
3/08/2016
Titles & IDs
Public title
Evaluation of Immunogenicity and Safety of a Booster Dose of Infanrix Hexa™ in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
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Scientific title
Immunogenicity and Safety Study of a Booster Dose of GSK Biologicals' Infanrix Hexa™ (217744) in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
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Secondary ID [1]
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0
2014-001120-30
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Secondary ID [2]
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201334
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Diphtheria
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0
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Hepatitis B
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0
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Acellular Pertussis
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0
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Haemophilus Influenzae Type b
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0
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Tetanus
0
0
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Poliomyelitis
0
0
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Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines
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0
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Condition category
Condition code
Infection
0
0
0
0
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Other infectious diseases
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Oral and Gastrointestinal
0
0
0
0
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Respiratory
0
0
0
0
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Other respiratory disorders / diseases
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Neurological
0
0
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0
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Other neurological disorders
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Metabolic and Endocrine
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0
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0
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Metabolic disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - Infanrix hexa
Experimental: dTpa Group - This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a single dose of Boostrix during pregnancy and a dose of placebo immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure
Active comparator: Control Group - This group will consist of healthy male or female infants, aged 9 months at the time of enrollment, born to mothers who received a dose of placebo during pregnancy and single dose of Boostrix immediately post-delivery. All enrolled subjects in this group who will come back for subsequent visit will receive a booster dose of Infanrix hexa co-administered with Prevenar 13 according to the routine national/local immunization or study procedure
Treatment: Other: Infanrix hexa
All subjects will receive Infanrix hexa co-administered with Prevenar13 as a booster dose.
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Intervention code [1]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Seroprotected Subjects Against Anti-diphtheria (Anti-D), Anti-tetanus (Anti-T), Anti-hepatitis B (Anti-HBs), Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3 and Anti-polyribosyl-ribitol Phosphate (Anti-PRP)
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Assessment method [1]
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Seroprotected subjects were defined as subjects with antibody concentrations/titres above or equal (=) the assay cut-offs that are accepted immunological correlates of protection.
0.1 International units per milliliter (IU/ml) for anti-D and anti-T, 10 milli-International units per milliliter (mIU/mL) for anti-HB's, 8 Effective Dose 50 (ED50) for anti-polio virus (type 1,2,3) and 0.15 microgram/milliliter (µg/mL) for anti-PRP were considered as immunological correlates of protection.
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Timepoint [1]
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At one month after the booster dose (Day 30)
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Primary outcome [2]
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Number of Subjects With a Booster Response to Pertussis Antigens (Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN))
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Assessment method [2]
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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 = 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 = 4 times the pre-vaccination antibody concentration, and
* for subjects with pre-vaccination antibody concentration = 4 times the assay cut-off, post-vaccination antibody concentration = 2 times the pre-vaccination antibody concentration
Seronegative (S-) subjects are those who have antibody concentration less than (\<) assay cut-off.
Seropositive (S+) subjects are those who have antibody concentration = assay cut-off prior to vaccination.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti- FHA and 2.187 IU/mL for anti-PRN
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Timepoint [2]
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At one month after the booster dose (Day 30)
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Secondary outcome [1]
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Number of Seroprotected Subjects Against Anti-diphtheria, Anti-tetanus, Anti-poliovirus Type 1, Anti-poliovirus Type 2, Anti-poliovirus Type 3, Anti-HBs and Anti-PRP.
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Assessment method [1]
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Seroprotected subjects were defined as subjects with antibody concentrations/titers above or equal (=) the assay cut-offs that are accepted immunological correlates of protection.
0.1 IU/mL for anti-D and anti-T, 10 mIU/mL for anti-HB's, 8 ED50 for anti-polio virus (type 1,2,3) and 0.15 µg/mL for anti-PRP were considered as immunological correlates of protection.
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Timepoint [1]
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Before the booster dose (Day 0)
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Secondary outcome [2]
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Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN
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Assessment method [2]
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Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN
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Timepoint [2]
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Before the booster dose (Day 0)
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Secondary outcome [3]
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Number of Seropositive Subjects for Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)
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Assessment method [3]
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Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off's for anti-pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) are 0.080 µg/mL, 0.075 µg/mL, 0.061 µg/mL, 0.198 µg/mL, 0.111 µg/mL, 0.102 µg/mL, 0.063 µg/mL, 0.66 µg/mL, 0.160 µg/mL, 0.111 µg/mL, 0.199 µg/mL, 0.163 µg/mL, 0.073 µg/mL respectively.
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Timepoint [3]
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Before the booster dose (Day 0)
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Secondary outcome [4]
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Anti-D, Anti-T, Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations
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Assessment method [4]
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Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in IU/mL.
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Timepoint [4]
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Before the booster dose (Day 0) and One month after the booster dose (Day 30)
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Secondary outcome [5]
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Anti-poliovirus Type 1, 2, 3 Antibody Titres
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Assessment method [5]
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Anti-Poliovirus type 1, 2 and 3 antibody titers were expressed as Geometric Mean Titers (GMT).
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Timepoint [5]
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Before the booster dose (Day 0) and One month after the booster dose (Day 30)
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Secondary outcome [6]
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Anti-HBs Antibody Concentrations
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Assessment method [6]
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Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in mIU/mL.
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Timepoint [6]
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Before the booster dose (Day 0) and One month after the booster dose (Day 30)
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Secondary outcome [7]
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Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and Anti-PRP Antibody Concentrations
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Assessment method [7]
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Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in µg/mL.
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Timepoint [7]
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Before the booster dose (Day 0) and One month after the booster dose (Day 30)
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Secondary outcome [8]
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Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.
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Assessment method [8]
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Seropositive subjects were defined as subjects whose antibody concentration/titre was greater than or equal to the assay cut-off.
Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti- FHA and 2.187 IU/mL for anti-PRN
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Timepoint [8]
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At one month after the booster dose (Day 30)
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Secondary outcome [9]
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Number of Subjects With Solicited Local Symptoms
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Assessment method [9]
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Assessed solicited local symptoms were pain, redness, swelling. Any redness, swelling is defined as a symptom with a surface diameter greater than 0 millimeter
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Timepoint [9]
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During the 4-day (Day 0-Day 3) follow-up period after booster vaccination of two vaccines (Infanrix hexa and Prevenar 13)
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Secondary outcome [10]
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Number of Subjects With Solicited General Symptoms
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Assessment method [10]
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Assessed solicited general symptoms were Drowsiness, Fever, Irritability/Fussiness and Loss of appetite.
Fever was defined as temperature =37.5 degree Celsius (°C) /99.5 degree Fahrenheit (°F) for oral, axillary or tympanic route, or =38.0°C/100.4°F on rectal route.
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Timepoint [10]
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During the 4-day (Day 0-Day 3) follow-up period after booster vaccination
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Secondary outcome [11]
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Number of Subjects With Unsolicited Adverse Events (AEs)
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Assessment method [11]
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An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Timepoint [11]
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During the 31-day (Day 0-Day 30) follow-up period after booster vaccination
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Secondary outcome [12]
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Number of Subjects With Serious Adverse Events (SAEs)
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Assessment method [12]
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SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, resulting in disability/incapacity
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Timepoint [12]
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From booster dose up to study end (approximately 6 or 7 months, per subject)
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Secondary outcome [13]
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Number of Subjects With an ASQ-3 Score (Ages & Stages Questionnaires, Third Edition) in the Black Zone
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Assessment method [13]
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Neurodevelopmental status was measured by ASQ-3 score scale \[ASQ-3, 2016\] in the black zone. The ASQ-3 included a series of questions designed to assess 5 areas of development (communication, gross motor, fine motor, problem solving, and personal-social). Any subject who scored below the cut-off i.e., a score more than 2 Standard Deviations (SDs) below the mean score for the U.S. reference group (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was to be referred to a developmental specialist for a formal neurodevelopmental assessment (using the Bayley Scale for Infant Development, Version III \[BSID-III\])
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Timepoint [13]
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At 9 months of age, 18 months of age, and 9 or 18 months of age
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Secondary outcome [14]
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Number of Subjects Referred for Formal Neurodevelopmental Evaluation Using BSID-III (Bayley Scale for Infant Development, Version III)
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Assessment method [14]
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Any subject who scored below the cut-off i.e., a score more than 2 Standard Deviations (SDs) below the mean score for the U.S. reference group (i.e., black zone in the score chart) in any of the 5 domains of the ASQ-3 was referred to a developmental specialist for a formal neurodevelopmental assessment (using the Bayley Scale for Infant Development, Version III BSID-III)
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Timepoint [14]
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At 9 months of age, 18 months of age, and 9 or 18 months of age
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Secondary outcome [15]
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Estimated Proportion of Infants With at Least One of the Indicators of Neurodevelopmental Impairment Using BSID-III (Bayley Scale for Infant Development, Version III)
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Assessment method [15]
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The estimated proportion (expressed in percentage) of infants with a BSID-III indicator of neurodevelopmental delay was based on ASQ-3 black zone indicator and subsequent BSID-III assessment using the following formula: 100 \* (Number of subjects with ASQ-3 below cut off / Number of enrolled subjects with available results) \* (Number of subjects with at least one indicator of neurodevelopmental delay using BSID III / Number of subjects referred for BSID III evaluation)
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Timepoint [15]
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At 9 months of age, 18 months of age, and 9 or 18 months of age
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Eligibility
Key inclusion criteria
* Subjects' parent(s)/Legally acceptable representatives (LAR(s)) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
* A male or female child 9 months of age at the time of enrolment.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Subjects born to mothers who were vaccinated in 116945 [DTPA (BOOSTRIX)-047] study and having completed their primary vaccination series as per protocol requirement in study 201330 [DTPA (BOOSTRIX)-048 PRI].
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Minimum age
9
Months
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Maximum age
19
Months
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
* Child in care
* Concurrently participating in another clinical study, within three months prior to the booster vaccine dose and at any time during the present booster study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period within six months prior to the booster vaccine dose. For corticosteroids, this will mean prednisone =0.5mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
* A vaccine not foreseen by the study protocol administered during the period starting from 30 days before the booster dose of study vaccine and ending 30 days after*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunization schedule, that are allowed at any time during the study period.
* In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its SPC or Product Information (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Major congenital defects.
* Serious chronic illness.
* Administration of immunoglobulins and/or any blood products during the period within three months before the booster dose of study vaccines or planned administration during the study period.
* Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination with Infanrix hexa and generally consisting of major alterations in consciousness, unresponsiveness, generalised or focal seizures that persist more than a few hours, with failure to recover within 24 hours.
* History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases since the conclusion visit of study 201330 [DTPA (BOOSTRIX)-048 PRI].
* Previous booster vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B and/or poliovirus since the conclusion visit of study 201330 [DTPA (BOOSTRIX)-048 PRI].
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (e.g: antigen, excipients).
* Hypersensitivity to latex.
* History of any neurological disorders or seizures.
* Any condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Acute disease and/or fever at the time of vaccination.
* Fever is defined as temperature = 37.5°C /99.5°F for oral, axillary or tympanic route, or = 38.0°C /100.4°F on rectal route.
* Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
19/09/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/03/2019
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Sample size
Target
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Accrual to date
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Final
551
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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GSK Investigational Site - Carlton
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Recruitment postcode(s) [1]
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3053 - Carlton
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Recruitment outside Australia
Country [1]
0
0
Canada
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State/province [1]
0
0
Alberta
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Country [2]
0
0
Canada
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State/province [2]
0
0
Nova Scotia
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Country [3]
0
0
Canada
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State/province [3]
0
0
Quebec
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Country [4]
0
0
Czechia
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State/province [4]
0
0
Brno
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Country [5]
0
0
Czechia
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State/province [5]
0
0
Hradec Kralove
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Country [6]
0
0
Czechia
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State/province [6]
0
0
Ostrava - Vitkovice
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Country [7]
0
0
Czechia
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State/province [7]
0
0
Praha 4
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Country [8]
0
0
Czechia
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State/province [8]
0
0
Praha
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Country [9]
0
0
Finland
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State/province [9]
0
0
Kokkola
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Country [10]
0
0
Finland
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State/province [10]
0
0
Oulu
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Country [11]
0
0
Finland
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State/province [11]
0
0
Seinajoki
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Country [12]
0
0
Finland
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State/province [12]
0
0
Tampere
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Country [13]
0
0
Finland
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State/province [13]
0
0
Turku
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Country [14]
0
0
Italy
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State/province [14]
0
0
Lombardia
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Country [15]
0
0
Italy
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State/province [15]
0
0
Piemonte
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Country [16]
0
0
Spain
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State/province [16]
0
0
Andalucia
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Country [17]
0
0
Spain
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State/province [17]
0
0
Antequera/Málaga
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Country [18]
0
0
Spain
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State/province [18]
0
0
Aravaca
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Country [19]
0
0
Spain
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State/province [19]
0
0
Burgos
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Country [20]
0
0
Spain
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State/province [20]
0
0
Madrid
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Country [21]
0
0
Spain
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State/province [21]
0
0
Majadahonda (Madrid)
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Country [22]
0
0
Spain
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State/province [22]
0
0
Móstoles
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Country [23]
0
0
Spain
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State/province [23]
0
0
Santiago de Compostela
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Country [24]
0
0
Spain
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State/province [24]
0
0
Sevilla
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to assess the immunogenicity and safety of the Infanrix hexa booster dose given at 11-18 months of age to infants who received primary vaccination at 6-14 weeks. All infants in this booster study were born to pregnant women who participated in the study 116945 \[DTPA (BOOSTRIX)-047\] and having received the full primary vaccination series as per protocol requirement in study 201330 \[DTPA (BOOSTRIX)-048.
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Trial website
https://clinicaltrials.gov/study/NCT02853929
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Trial related presentations / publications
Martinon-Torres F, Halperin SA, Nolan T, Tapiero B, Perrett KP, de la Cueva IS, Garcia-Sicilia J, Stranak Z, Vanderkooi OG, Kosina P, Rumlarova S, Virta M, Arribas JMM, Miranda-Valdivieso M, Novas BA, Bozensky J, Ortega MJC, Amador JTR, Baca M, Palomino EE, Zuccotti GV, Janota J, Marchisio PG, Kostanyan L, Meyer N, Ceregido MA, Cheuvart B, Kuriyakose SO, Mesaros N. Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial. Vaccine. 2021 Mar 12;39(11):1598-1608. doi: 10.1016/j.vaccine.2021.02.001. Epub 2021 Feb 19.
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Public notes
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Contacts
Principal investigator
Name
0
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GSK Clinical Trials
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Address
0
0
GlaxoSmithKline
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
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When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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Available to whom?
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.
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/29/NCT02853929/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/29/NCT02853929/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT02853929