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Trial record 1 of 29 for:    infanrix | gsk | Phase 4
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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02853929
Recruitment Status : Completed
First Posted : August 3, 2016
Results First Posted : January 14, 2020
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Diphtheria Hepatitis B Acellular Pertussis Haemophilus Influenzae Type b Tetanus Poliomyelitis Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines Biological: Infanrix hexa Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 551 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official 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
Actual Study Start Date : September 19, 2016
Actual Primary Completion Date : March 19, 2019
Actual Study Completion Date : March 19, 2019


Arm Intervention/treatment
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
Biological: Infanrix hexa
All subjects will receive Infanrix hexa co-administered with Prevenar13 as a booster dose.

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
Biological: Infanrix hexa
All subjects will receive Infanrix hexa co-administered with Prevenar13 as a booster dose.




Primary Outcome Measures :
  1. 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) [ Time Frame: At one month after the booster dose (Day 30) ]

    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.


  2. Number of Subjects With a Booster Response to Pertussis Antigens (Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN)) [ Time Frame: At one month after the booster dose (Day 30) ]

    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



Secondary Outcome Measures :
  1. 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. [ Time Frame: Before the booster dose (Day 0) ]

    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.


  2. Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN [ Time Frame: Before the booster dose (Day 0) ]

    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


  3. Number of Seropositive Subjects for Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) [ Time Frame: Before the booster dose (Day 0) ]

    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.


  4. Anti-D, Anti-T, Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations [ Time Frame: Before the booster dose (Day 0) and One month after the booster dose (Day 30) ]
    Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in IU/mL.

  5. Anti-poliovirus Type 1, 2, 3 Antibody Titres [ Time Frame: Before the booster dose (Day 0) and One month after the booster dose (Day 30) ]
    Anti-Poliovirus type 1, 2 and 3 antibody titers were expressed as Geometric Mean Titers (GMT).

  6. Anti-HBs Antibody Concentrations [ Time Frame: Before the booster dose (Day 0) and One month after the booster dose (Day 30) ]
    Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in mIU/mL.

  7. Anti-pneumococcal Serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and Anti-PRP Antibody Concentrations [ Time Frame: Before the booster dose (Day 0) and One month after the booster dose (Day 30) ]
    Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in µg/mL.

  8. Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN. [ Time Frame: At one month after the booster dose (Day 30) ]

    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


  9. Number of Subjects With Solicited Local Symptoms [ Time Frame: During the 4-day (Day 0-Day 3) follow-up period after booster vaccination of two vaccines (Infanrix hexa and Prevenar 13) ]
    Assessed solicited local symptoms were pain, redness, swelling. Any redness, swelling is defined as a symptom with a surface diameter greater than 0 millimeter

  10. Number of Subjects With Solicited General Symptoms [ Time Frame: During the 4-day (Day 0-Day 3) follow-up period after booster vaccination ]

    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.


  11. Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: During the 31-day (Day 0-Day 30) follow-up period after booster vaccination ]
    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.

  12. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From booster dose up to study end (approximately 6 or 7 months, per subject) ]
    SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, resulting in disability/incapacity

  13. Number of Subjects With an ASQ-3 Score (Ages & Stages Questionnaires, Third Edition) in the Black Zone [ Time Frame: At 9 months of age, 18 months of age, and 9 or 18 months of age ]
    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])

  14. Number of Subjects Referred for Formal Neurodevelopmental Evaluation Using BSID-III (Bayley Scale for Infant Development, Version III) [ Time Frame: At 9 months of age, 18 months of age, and 9 or 18 months of age ]
    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)

  15. Estimated Proportion of Infants With at Least One of the Indicators of Neurodevelopmental Impairment Using BSID-III (Bayley Scale for Infant Development, Version III) [ Time Frame: At 9 months of age, 18 months of age, and 9 or 18 months of age ]
    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)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   9 Months to 19 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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].

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02853929


Locations
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Australia, Victoria
GSK Investigational Site
Carlton, Victoria, Australia, 3053
Canada, Alberta
GSK Investigational Site
Calgary, Alberta, Canada, T3B 6A8
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H3T 1C5
Czechia
GSK Investigational Site
Brno, Czechia, 613 00
GSK Investigational Site
Hradec Kralove, Czechia, 500 02
GSK Investigational Site
Ostrava - Vitkovice, Czechia, 703 84
GSK Investigational Site
Praha 4, Czechia, 140 59
GSK Investigational Site
Praha, Czechia, 14700
Finland
GSK Investigational Site
Kokkola, Finland, 67100
GSK Investigational Site
Oulu, Finland, 90220
GSK Investigational Site
Seinajoki, Finland, 60100
GSK Investigational Site
Tampere, Finland, 33100
GSK Investigational Site
Turku, Finland, 20520
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Milano, Lombardia, Italy, 20142
GSK Investigational Site
Milano, Lombardia, Italy, 20154
GSK Investigational Site
Novara, Piemonte, Italy, 28100
Spain
GSK Investigational Site
Malaga, Andalucia, Spain, 29004
GSK Investigational Site
Antequera/Málaga, Spain, 29200
GSK Investigational Site
Aravaca, Spain, 28023
GSK Investigational Site
Burgos, Spain, 09006
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Madrid, Spain, 28050
GSK Investigational Site
Majadahonda (Madrid), Spain, 28222
GSK Investigational Site
Móstoles, Spain, 28938
GSK Investigational Site
Santiago de Compostela, Spain, 15706
GSK Investigational Site
Sevilla, Spain, 41014
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] December 12, 2016
Statistical Analysis Plan  [PDF] March 22, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02853929    
Other Study ID Numbers: 201334
2014-001120-30 ( EudraCT Number )
First Posted: August 3, 2016    Key Record Dates
Results First Posted: January 14, 2020
Last Update Posted: January 14, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Pertussis
Immunogenicity
Poliomyelitis
Tetanus
Hepatitis B
Diptheria
Additional relevant MeSH terms:
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Hepatitis A
Influenza, Human
Hepatitis B
Whooping Cough
Tetanus
Diphtheria
Poliomyelitis
Hepatitis
Tetany
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Respiratory Tract Infections
Orthomyxoviridae Infections
Respiratory Tract Diseases
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Clostridium Infections
Gram-Positive Bacterial Infections