Clinical trial NCT02798952: A Study to Evaluate Persistence of Hepatitis B Antibodies, Immunogenicity and Safety of Engerix™-B Kinder Challenge Dose, in Adolescents Vaccinated With Four Doses of Infanrix™ Hexa During Infancy
Official title: Persistence of Hepatitis B Antibodies, Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine, Engerix™-B Kinder (SKF103860) Challenge Dose, in Adolescents Vaccinated With Four Doses of Infanrix™ Hexa (SB217744) During Infancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B
Keywords: Hepatitis B antibodies
Safety
Challenge dose
Persistence
Engerix B Kinder
Infanrix hexa
Immunogenicity
Adolescents
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 302
Sex: ALL
Minimum age (years): 14
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the long-term persistence of immunity to hepatitis B in adolescents aged 14-15 years who were vaccinated with four doses of Infanrix™-Hexa in the first two years of life and to assess the anamnestic response, immunogenicity, safety and reactogenicity of a single challenge dose of the hepatitis B vaccine Engerix™-B Kinder.


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.
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
* In addition to the informed consent that will be signed by the parents/LAR(s), written informed assent of the subject will be sought.
* A male or female between the ages of 14 to 15 at the time of vaccination.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Subjects with documented evidence of previous vaccination with four consecutive doses of Infanrix hexa as part of routine vaccination in Germany: three doses of primary vaccination received by 9 months of age and one booster dose received between 11 and 18 months of age.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the dose of study vaccine, or planned use during the study period.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs at any time during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the dose and ending 30 days after the dose of HBV vaccine administration with the exception of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, which can be given as part of routine vaccination practice. Seasonal or pandemic influenza vaccine can be given at any time during the study, and according to the Summary of Product Characteristics and national recommendations.
* 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).
* Evidence of previous hepatitis B booster vaccination since administration of the fourth dose of Infanrix hexa booster in the second year of life.
* History of or intercurrent hepatitis B disease.
* Hepatitis B vaccination at birth.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* 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 or serious chronic illness including thrombocytopenia and bleeding disorders.
* 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 for oral, axillary or tympanic route, or ≥38.0°C for rectal route.
  * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the dose of study vaccine or planned administration during the study period.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.

Primary outcomes:
measure: Anti-Hepatitis B Surface (Anti-HBs) Antibody Concentrations
timeFrame: At Day 30.
Secondary outcomes:
measure: Anti-HBs Antibody Concentrations
timeFrame: At Day 0
measure: Number of Seropositive Subjects for Anti-HBs.
timeFrame: At Day 0 and Day 30
measure: Number of Seroprotected Subjects for Anti-HBs.
timeFrame: At Day 0 and day 30
measure: Number of Subjects With Anti-HBs Concentrations Above the Cut-off.
timeFrame: At Day 0 and Day 30
measure: Number of Subjects With an Anamnestic Response to the Hepatitis B Challenge Dose.
timeFrame: At Day 30
measure: Number of Subjects With Any Solicited Local and General Symptoms.
timeFrame: Within 4 days (Day 0 - Day 3) after the vaccination
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days (Day 0 - Day 30) after the vaccination.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 to Day 30
Other outcomes:
Locations:
city: Kehl
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuttlingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Bindlach
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Cham
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Frankenthal
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Wurzen
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bramsche
country: Germany
facility: GSK Investigational Site
city: Moenchengladbach
country: Germany
facility: GSK Investigational Site
city: Neumuenster
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schwarz TF, Behre U, Adelt T, Donner M, Suryakiran PV, Janssens W, Mesaros N, Panzer F. Long-term antibody persistence against hepatitis B in adolescents 14-15-years of age vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy. Hum Vaccin Immunother. 2019;15(1):235-241. doi: 10.1080/21645515.2018.1509658. Epub 2018 Sep 11.