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Immunogenicity and Safety Study of Infanrix Hexa in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery

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ClinicalTrials.gov Identifier: NCT02422264
Recruitment Status : Completed
First Posted : April 21, 2015
Results First Posted : June 10, 2019
Last Update Posted : July 9, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' Infanrix hexa, given in the primary vaccination schedule to infants born to pregnant women who participated in study 116945 [DTPA (BOOSTRIX)-047]. This study will help us evaluate if the presence of transplacentally transferred maternal antibodies interfere with the immune response to primary vaccination with Infanrix hexa and a co-administered pneumococcal conjugate vaccine given as a part of this study in infants.

Condition or disease Intervention/treatment Phase
Acellular Pertussis Tetanus Poliomyelitis Diphtheria Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines Biological: Infanrix hexa Drug: Prevnar13 Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 601 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GSK Biologicals' Combined Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated Polio-virus and Haemophilus Influenzae Type b Vaccine (Infanrix Hexa™) (217744) in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
Actual Study Start Date : January 22, 2016
Actual Primary Completion Date : March 7, 2018
Actual Study Completion Date : March 7, 2018


Arm Intervention/treatment
Experimental: dTpa Group
This group will consist of infants born to mothers belonging to the dTpa Group in study 116945 [DTPA (BOOSTRIX)-047] i.e. who received a single dose of BoostrixTM during pregnancy and a dose of placebo immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®.
Biological: Infanrix hexa
• All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.

Drug: Prevnar13
• All subjects will receive Infanrix hexa co-administered with Prevenar13* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. *In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.

Active Comparator: Control Group
This group will consist of infants born to mothers belonging to the Control group in study 116945 [DTPA (BOOSTRIX)-047], i.e. who received a single dose of placebo during pregnancy and a dose of BoostrixTM immediately post-delivery. All infants in this group will receive Infanrix hexaTM co-administered with Prevenar 13®.
Biological: Infanrix hexa
• All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.

Drug: Prevnar13
• All subjects will receive Infanrix hexa co-administered with Prevenar13* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. *In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.




Primary Outcome Measures :
  1. Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Vaccine response to the PT, FHA and PRN antigens, is defined as the appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations lower than (<) the cut-off value of the assay), or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations greater than or equal to (≥) the cut-off value of the assay). Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, 2.187 IU/mL for anti-PRN.

  2. Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off [ Time Frame: 1 month after the last dose of the primary vaccination ]
    A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.1 International Units per milliliter (IU/mL).

  3. Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off [ Time Frame: 1 month after the last dose of the primary vaccination ]
    A seroprotected subject is a subject whose antibody concentration/titre was ≥ to the level defining clinical protection, of 10 micro International Units per milliliter (mIU/mL).

  4. Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 [ Time Frame: 1 month after the last dose of the primary vaccination ]
    A seroprotected subject is a subject whose antibody titre was ≥ the level defining clinical protection, of 8 ED50.

  5. Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off [ Time Frame: 1 month after the last dose of the primary vaccination ]
    A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.15 micrograms per milliliter (µg/mL).


Secondary Outcome Measures :
  1. Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. [ Time Frame: Before the first dose of Infanrix hexa ]
    A seroprotected subject is a subject whose antibody concentration was ≥ the level defining clinical protection, of 0.1 IU/mL.

  2. Anti-D and Anti-T Antibody Concentrations [ Time Frame: Before the first dose of Infanrix hexa ]
    Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL.

  3. Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. [ Time Frame: Before the first dose of Infanrix hexa ]
    A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN

  4. Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations [ Time Frame: Before the first dose of Infanrix hexa ]
    Anti-PT, anti-FHA and anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL.

  5. Anti-D and Anti-T Antibody Concentrations [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL.

  6. Anti-Polio Type 1, 2 and 3 Antibody Titers [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Anti-Polio type 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMT).

  7. Anti-HBs Antibody Concentrations [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Anti-HBs antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL.

  8. Anti-PRP Antibody Concentrations [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Anti-PRP antibody concentrations were expressed as GMCs and measured in µg/mL.

  9. Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Anti-PT, anti-FHA, anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL.

  10. Anti-pneumococcal Antibody Concentrations [ Time Frame: 1 month after the last dose of the primary vaccination ]
    Assessed anti-pneumococcal serotypes were (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), expressed as GMCs and measured in µg/mL.

  11. Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. [ Time Frame: 1 month after the last dose of the primary vaccination ]
    A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN

  12. Number of Subjects With Solicited Local Symptoms [ Time Frame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Solicited local symptoms were assessed by each and across dose.

  13. Number of Subjects With Solicited General Symptoms [ Time Frame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination ]
    Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite and fever [defined as axillary route temperature ≥ 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Solicited general symptoms were assessed by each and across dose.

  14. Number of Subjects With Unsolicited Adverse Events [ Time Frame: During the 31-day (days 0-30) follow-up period after each vaccination ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  15. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From Day 0, prior to vaccination until the study end, at Month 3 or 5 (depending on vaccination schedule of the country) ]
    SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.



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:   6 Weeks to 14 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects' parent(s)/Legally Acceptable Representative(s) [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 between, 6 and 14 weeks of age (including 6 weeks and up to and including 14 weeks and 6 days of age) at the time of the first vaccination.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Born to a mother enrolled in study 116945 [DTPA (BOOSTRIX)-047].
  • Medically stable* prematurely born infants, born after a gestation period of 27-36 weeks may be enrolled in the study at the discretion of the investigator.

    • Medically stable refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study vaccine.

Exclusion Criteria:

  • Child in care
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting at birth prior to the first 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).
  • Administration of any chronic drug therapy to be continued during the study period.
  • A vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of vaccine and ending 30 days after*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunisation 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 immunisation 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 package insert (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained.
  • 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 vaccine/product (pharmaceutical product or device).
  • Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, and/or poliovirus since birth.
  • History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition including severe combined immunodeficiency disease (SCID), 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 vaccine.
  • Major congenital defects
  • Serious chronic illness.
  • History of any neurological disorders or seizures.
  • Acute disease and/or fever at the time of enrolment.

    • Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic route, or ≥38.0°C/100.4°F for 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.
  • Administration of immunoglobulins and/or any blood products during the period starting at birth before the first dose of study vaccines or planned administration during the study period.
  • Hypersensitivity to latex.

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): NCT02422264


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
GSK Investigational Site
Torino, Piemonte, Italy, 10126
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] September 6, 2016
Statistical Analysis Plan  [PDF] July 16, 2018


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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02422264     History of Changes
Other Study ID Numbers: 201330
2014-001117-41 ( EudraCT Number )
First Posted: April 21, 2015    Key Record Dates
Results First Posted: June 10, 2019
Last Update Posted: July 9, 2019
Last Verified: June 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
Additional relevant MeSH terms:
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Whooping Cough
Tetanus
Diphtheria
Influenza, Human
Hepatitis B
Poliomyelitis
Hepatitis
Tetany
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Orthomyxoviridae Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Hepadnaviridae Infections
DNA Virus Infections
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Infection
Clostridium Infections
Gram-Positive Bacterial Infections
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Hypocalcemia