Clinical trial NCT01453998: Safety and Immunogenicity of a Booster Dose of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744)
Official title: Safety and Immunogenicity of a Booster Dose of New Formulations of GlaxoSmithKline Biologicals' DTPa-HBV-IPV/Hib Vaccine (GSK217744)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acellular Pertussis
Hepatitis B
Haemophilus Influenzae Type b
Tetanus
Diphtheria
Poliomyelitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-18
Enrollment: 657
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
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 assess the immunogenicity, safety and reactogenicity of the booster vaccine dose of 2 new formulations of DTPa-HBV-IPV/Hib administered between 12 and 15 months of age, and the immune persistence following the primary series. All children in this booster study received a primary vaccination at 2, 3 and 4 months of age in study 113948 (NCT01248884). No new subjects will be enrolled in this booster study.


Eligibility criteria: Inclusion Criteria:

* Subjects who participated in the study 113948 (NCT01248884) and received three doses of the new or licensed DTPa-HBV-IPV/Hib study vaccine.
* A male or female child between, and including, 12 and 15 months of age at the time of the booster vaccination.
* Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visit).
* Written informed consent obtained from the parent(s)/LAR(s) of the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the study.

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 booster dose of study vaccine, or planned use during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose.
* Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period.
* Participation in another clinical study within three months prior to enrolment in the present booster study or 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 product (pharmaceutical product or device).
* Evidence of previous or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hib vaccination or disease since the conclusion visit of study 113948 (NCT01248884).
* Serious chronic illness.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* History of any neurological disorders or seizures.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the booster dose of study vaccine or planned administration during the study period.
* Occurrence of any of the following events following previous administration of the study vaccine constitutes an absolute contraindication to further dosing.

  * Anaphylactic or other hypersensitivity reaction.
  * Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, with failure to recover within 24 hours.
  * Temperature of ≥ 40.0°C (axillary) or 40.5°C (rectal) within 48 hours of vaccination, not due to another identifiable cause.
  * Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination.
  * Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting ≥ 3 hours.
  * Seizures with or without fever occurring within 3 days of vaccination.

The following condition is temporary or self-limiting, and a subject may be vaccinated once the condition has resolved if no other exclusion criteria is met:

• Acute disease and/or fever at the time of enrolment.

* Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥ 38.0° on rectal setting.
* Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.

Primary outcomes:
measure: Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-D and Anti-T Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects Against Anti-Hepatitis B (Anti-HBs) Antigens
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects Against Anti-HBs Antigens
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-poliovirus Type 1, 2 and 3
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP)
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-PRP
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN)
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-PT, Anti-FHA and Anti-PRN
timeFrame: 1 month post booster vaccination (subjects enrolled after protocol amendment 2)
Secondary outcomes:
measure: Concentrations for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies
timeFrame: Before (PRE) and 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-D and Anti-T Antibodies
timeFrame: Before (PRE) 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-D and Anti-T Antibodies
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN)
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-PT, Anti-FHA and Anti-PRN
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Number of Seropositive Subjects for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN)
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seropositive Subjects for Anti-PT, Anti-FHA, Anti-PRN
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Anti-Hepatitis B (Anti-HBs) Antibody Concentrations
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2))
measure: Anti-HBs Antibody Concentrations
timeFrame: 1 month post booster vaccination (POST) ( subjects enrolled after protocol amendment 2)
measure: Anti-Hepatitis B (Anti-HBs) Antibody Concentration
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Anti-HBs Antibody Concentrations
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects Against Anti-Hepatitis B (Anti-HBs) Antigens
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects Against Anti-HBs Antigens
timeFrame: Before (PRE) booaster vaccination (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-poliovirus Types 1, 2, 3
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Concentration for Anti-poliovirus Types 1, 2, 3
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-poliovirus Types 1, 2 and 3
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Concentration for Anti-poliovirus Type 1, 2 and 3
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-poliovirus Type 1, 2 and 3
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects Against Anti-Poliovirus Type 1, 2 and 3
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-PRP Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibodies
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-polyribosyl-ribitol Phosphate Antibodies
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2))
measure: Number of Seropositive Subjects for Anti-Pertussis Toxoid (Anti-PT), Anti-Filamentous Haemagglutinin (Anti-FHA), Anti-Pertactin (Anti-PRN)
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Number of Seropositive Subjects for Anti-PT, Anti-FHA, Anti-PRN
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-polyribosyl-ribitol Phosphate (Anti-PRP)
timeFrame: Before (PRE) booster vaccination (subjects enrolled before protocol amendment 2)
measure: Number of Seroprotected Subjects for Anti-PRP
timeFrame: Before (PRE) booster vaccination (subjects enrolled after protocol amendment 2)
measure: Concentrations for Anti-pneumococcal (Anti-PNE) Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Concentrations for Anti-PNE Antibodies
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Seropositive Subjects for Anti-PNE Serotypes
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Subjects With Booster Response to Anti-pertussis Antigens (Anti-PT, Anti-FHA and Anti-PRN)
timeFrame: 1 month post booster vaccination (POST) (subjects enrolled before protocol amendment 2)
measure: Number of Subjects With Booster Response to Anti-pertussis Antigens
timeFrame: 1 month poste booster vaccination (POST) (subjects enrolled after protocol amendment 2)
measure: Number of Subjects Reporting Any Solicited Local Symptoms
timeFrame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2)
measure: Number of Subjects Reporting Any Solicited Local Symptom
timeFrame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2)
measure: Number of Subjects Reporting Any Solicited General Symptoms
timeFrame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled before protocol amendment 2)
measure: Number of Subjects Reporting Any Solicited General Symptom
timeFrame: During the 4-day (Days 0-3) post-vaccination period. (subjects enrolled after protocol amendment 2)
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs)
timeFrame: Within the 31-day (Days 0-30) follow up period after vaccination. (subjects enrolled before protocol amendment 2)
measure: Number of Subjects Reporting Any Unsolicited AEs
timeFrame: Within the 31-day (Days 0-30) follow up period after vaccination. (subjects enrolled after protocol amendment 2)
measure: Number of Subjects Reporting Any Serious Adverse Events (SAEs)
timeFrame: During the entire study period (Days 0-30). (subjects enrolled before protocol amendment 2)
measure: Number of Subjects Reporting Any SAEs
timeFrame: During the entire study period (Days 0-30). (subjects enrolled after protocol amendment 2)
Other outcomes:
Locations:
city: Santo Domingo, Distrito Nacional
country: Dominican Republic
facility: GSK Investigational Site
city: Santo Domingo
country: Dominican Republic
facility: GSK Investigational Site
city: Espoo
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: Lahti
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
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: Vantaa
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Rivera L, Korhonen T, Ahonen A, Cheuvart B, Hezareh M, Janssens W, Mesaros N. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa. Hum Vaccin Immunother. 2017 Jul 3;13(7):1505-1515. doi: 10.1080/21645515.2017.1294294. Epub 2017 Mar 24.