Clinical trial NCT02096263: Study to Determine the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals; Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants
Official title: Immunogenicity and Safety Study of GSK Biologicals' Infanrix Hexa at 2, 4 and 6 Months of Age in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Poliomyelitis
Diphtheria
Haemophilus Influenzae Type b
Tetanus
Acellular Pertussis
Hepatitis B
Keywords: Infants
Safety
Healthy
Infanrix Hexa
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-03-26
Enrollment: 585
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Antibody Concentrations for Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN).
timeFrame: At Month 5, one month after the third dose of the primary vaccination.
Secondary outcomes:
measure: Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.
timeFrame: At Month 5, one month after the third dose of the primary vaccination.
measure: Number of Seroprotected Subjects Against Tetanus (T).
timeFrame: At Month 5, one month after the third dose of the primary vaccination.
measure: Number of Seroprotected Subjects Against Diphtheria (D).
timeFrame: At Month 5, one month after the third dose of the primary vaccination.
measure: Antibody Concentrations for Anti-T.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Antibody Concentrations for Anti-D.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Antibody Titres for Anti-polio Types 1, 2 and 3.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Number of Seroprotected Subjects Against Polyribosyl Ribitol Phosphate (Anti-PRP).
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Number of Subjects With Anti-PRP Antibody Concentrations ≥ 1 µg/mL.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Antibody Concentrations for Anti-PRP.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Number of Seroprotected Subjects Against Hepatitis B (Anti-HBs).
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Antibody Concentrations for Anti-HBs.
timeFrame: At Month 5, one month after the third dose of the primary vaccination
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 1
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 2
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 3
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following any dose.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 1.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 2.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following Dose 3.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 4-day (Days 0-3) post-vaccination period following any dose.
measure: Number of Subjects With Specific Adverse Events (AEs).
timeFrame: From Month 0 up to 6 months post primary-vaccination (Month 10)
measure: Number of Subjects With Unsolicited AEs.
timeFrame: During the 31-day (Days 0-30) post-primary vaccination period.
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 up to 6 months post-primary vaccination (Month 10)
measure: Number of Seroprotected Subjects Against Anti-T.
timeFrame: 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)]
measure: Number of Seroprotected Subjects Against Anti-D.
timeFrame: 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)]
measure: Antibody Concentrations for Anti-T.
timeFrame: 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)]
measure: Antibody Concentrations for Anti-D.
timeFrame: 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)]
measure: Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN.
timeFrame: 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)]
measure: Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN.
timeFrame: 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)]
measure: Number of Subjects With a Booster Response for Anti-PT, Anti-FHA and Anti-PRN.
timeFrame: At Visit 6 [At Month 14-17 one month after the booster dose (Dose 4)]
measure: Number of Seroprotected Subjects Against Anti-PRP.
timeFrame: 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)]
measure: Number of Subjects With Anti-PRP Antibody Concentrations ≥ 1 µg/mL.
timeFrame: 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)]
measure: Antibody Concentrations for Anti-PRP.
timeFrame: 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)]
measure: Number of Seroprotected Subjects Against Anti-polio Types 1, 2 and 3.
timeFrame: At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
measure: Antibody Titres for Anti-polio Types 1, 2 and 3.
timeFrame: At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
measure: Number of Seroprotected Subjects Against Anti-HBs.
timeFrame: At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
measure: Antibody Concentrations for Anti-HBs.
timeFrame: At Visit 5 [At Month 13-16 before the booster dose (Dose 4)]
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-booster vaccination.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 4-day (Days 0-3) post-booster vaccination.
measure: Number of Subjects With Specific AEs.
timeFrame: During the 31-day (Days 0-30) post-booster vaccination.
measure: Number of Subjects With Unsolicited AEs.
timeFrame: During the 31-day (Days 0-30) post-booster vaccination.
measure: Number of Subjects With SAEs.
timeFrame: During the 31-day (Days 0-30) post-booster vaccination.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fayetteville
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Daly City
country: United States
facility: GSK Investigational Site
state: California
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Hayward
country: United States
facility: GSK Investigational Site
state: California
city: Oakland
country: United States
facility: GSK Investigational Site
state: California
city: Pleasanton
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Jose
country: United States
facility: GSK Investigational Site
state: California
city: Santa Clara
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Altamonte Springs
country: United States
facility: GSK Investigational Site
state: Florida
city: Orange City
country: United States
facility: GSK Investigational Site
state: Florida
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Woodstock
country: United States
facility: GSK Investigational Site
state: Georgia
city: Nampa
country: United States
facility: GSK Investigational Site
state: Idaho
city: Augusta
country: United States
facility: GSK Investigational Site
state: Kansas
city: Newton
country: United States
facility: GSK Investigational Site
state: Kansas
city: Topeka
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Nicholasville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Columbia
country: United States
facility: GSK Investigational Site
state: Maryland
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Erie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sellersville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Layton
country: United States
facility: GSK Investigational Site
state: Utah
city: Payson
country: United States
facility: GSK Investigational Site
state: Utah
city: Provo
country: United States
facility: GSK Investigational Site
state: Utah
city: Saint George
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: South Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: West Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Ellensburg
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.