Clinical trial NCT02422264: Immunogenicity and Safety Study of Infanrix Hexa in Healthy Infants Born to Mothers Vaccinated With Boostrix™ During Pregnancy or Immediately Post-delivery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acellular Pertussis
Tetanus
Poliomyelitis
Diphtheria
Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-04-21
Enrollment: 601
Sex: ALL
Minimum age (years): 6
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off
timeFrame: 1 month after the last dose of the primary vaccination
Secondary outcomes:
measure: Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off.
timeFrame: Before the first dose of Infanrix hexa
measure: Anti-D and Anti-T Antibody Concentrations
timeFrame: Before the first dose of Infanrix hexa
measure: Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off.
timeFrame: Before the first dose of Infanrix hexa
measure: Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
timeFrame: Before the first dose of Infanrix hexa
measure: Anti-D and Anti-T Antibody Concentrations
timeFrame: 1 month after the last dose of the primary vaccination
measure: Anti-Polio Type 1, 2 and 3 Antibody Titers
timeFrame: 1 month after the last dose of the primary vaccination
measure: Anti-HBs Antibody Concentrations
timeFrame: 1 month after the last dose of the primary vaccination
measure: Anti-PRP Antibody Concentrations
timeFrame: 1 month after the last dose of the primary vaccination
measure: Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations
timeFrame: 1 month after the last dose of the primary vaccination
measure: Anti-pneumococcal Antibody Concentrations
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off.
timeFrame: 1 month after the last dose of the primary vaccination
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination
measure: Number of Subjects With Unsolicited Adverse Events
timeFrame: During the 31-day (days 0-30) follow-up period after each vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0, prior to vaccination until the study end, at Month 3 or 5 (depending on vaccination schedule of the country)
Other outcomes:
Locations:
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Vitkovice
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha
country: Czechia
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Novara
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Malaga
country: Spain
facility: GSK Investigational Site
state: Andalucia
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Aravaca
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Móstoles
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Perrett KP, Halperin SA, Nolan T, Carmona Martinez A, Martinon-Torres F, Garcia-Sicilia J, Virta M, Vanderkooi OG, Zuccotti GV, Manzoni P, Kostanyan L, Meyer N, Ceregido MA, Cheuvart B, Kuriyakose SO, Stranak Z, Merino Arribas JM, Cilleruelo Ortega MJ, Miranda-Valdivieso M, Arias Novas B, Ramos Amador JT, Omenaca F, Baca M, Marchisio PG, Mesaros N. Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial. Vaccine. 2020 Feb 18;38(8):2105-2114. doi: 10.1016/j.vaccine.2019.10.104. Epub 2019 Nov 24.