Development of Read-outs in Healthy, Hepatitis B Virus Naive Adults Vaccinated With the Hepatitis B Surface Antigen (HBsAg) in Combination With a GlaxoSmithKline (GSK) Biologicals' Adjuvant System

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Public Private Partnership with Institute for Medical Immunology (Universite Libre de Bruxelles)
Region Wallonne
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01777295
First received: January 24, 2013
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

This study aims to develop innovative immunological read-outs and new technologies in order to further characterise the early immune response and its kinetics as well as the adaptive immune responses to adjuvanted vaccines.

This study will also evaluate the reactogenicity in healthy, hepatitis B virus naive adults vaccinated with the hepatitis B surface antigen in combination with a GSK Biologicals' Adjuvant System.


Condition Intervention Phase
Hepatitis B
Biological: Adjuvanted Hepatitis B surface antigen (HBsAg) candidate vaccine GSK2231392A.
Biological: EngerixTM-B
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Development of Read-outs to Detect and Characterise the Early and Adaptive Immune Responses in Healthy, Hepatitis B Virus Naive Adults Vaccinated With the Hepatitis B Surface Antigen in Combination With a GSK Biologicals' Adjuvant System

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Innate/early immune response: Soluble mediators from the innate/early immune response in all subjects (Step 1 only). [ Time Frame: Day of study product administration (Day -30, Day 0 and Day 30) and during a 7-day follow-up period post study product administration. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adaptive response: Classical cellular and humoral immune response to components of the study vaccine in all subjects (Step 1 and 2). [ Time Frame: Day 0, Day 44, Day 60, Day 180 and Day 210. ] [ Designated as safety issue: No ]
  • Occurrence of solicited and non-serious unsolicited adverse events (AEs) (Step 1 and 2). [ Time Frame: Day of study product administration (Day -30 [step 1 only], Day 0 and Day 30 [both Steps]) and during a maximum of 28 day follow-up period post study product administration. ] [ Designated as safety issue: No ]
  • Occurrence of any serious adverse event (SAE) (Step 1 and 2). [ Time Frame: During the entire study period. ] [ Designated as safety issue: No ]
  • Occurrence of any Potential Immune-Mediated Disease (pIMD) (Step 1 and 2). [ Time Frame: During the entire study period. ] [ Designated as safety issue: No ]
  • Occurrence of any new medical condition requiring medical attention (Step 1 and 2). [ Time Frame: During the entire study period. ] [ Designated as safety issue: No ]
  • Safety laboratory parameters (Step 1 and 2). [ Time Frame: At Day 0, Day 1, Day 7, Day 30, Day 31, Day 37 and Day 60. ] [ Designated as safety issue: No ]
  • Vital signs at protocol defined time-points (Step 1 and 2). [ Time Frame: Day of study product administration (Day -30 [step 1 only], Day 0 and Day 30 [both Steps]) and during a 7 day follow-up period post study product administration. ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: February 2013
Estimated Study Completion Date: November 2015
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Subjects in this group will receive GSK Biologicals' adjuvanted investigational vaccine and a placebo (Step 1).
Biological: Adjuvanted Hepatitis B surface antigen (HBsAg) candidate vaccine GSK2231392A.
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.
Active Comparator: Group B
Subjects in this group will receive Engerix-B and a placebo (Step 1).
Biological: EngerixTM-B
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.
Experimental: Group C
Subjects in this group will receive GSK Biologicals' adjuvanted investigational vaccine (Step 2).
Biological: Adjuvanted Hepatitis B surface antigen (HBsAg) candidate vaccine GSK2231392A.
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.
Active Comparator: Group D
Subjects in this group will receive Engerix-B (Step 2).
Biological: EngerixTM-B
Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

Detailed Description:

This study will be conducted in 2 steps:

  • Step 1 will aim at the development of innate and adaptive read-outs. This evaluation of the early immune response will lead to the selection of the most informative time-points for Step 2.
  • Step 2 will gather additional data on the cellular component of the vaccine-induced immune response at selected time-points and will evaluate additional exploratory read-outs of the innate immune response.

There will be 2 study groups in each step. The entire study period for Step 1 is from Day -30 to Day 210 (240 days). The entire study period for Step 2 is from Day 0 to Day 210 (210 days).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
  • A male or female between, and including, 18 and 45 years of age at the time of first study product administration.
  • Written informed consent obtained from the subject.
  • Healthy subjects, in the opinion of the investigator, as established by medical history, clinical examination, and clinical laboratory assessment with no active disease that could interfere with the study endpoints, before entering into the study.
  • Body Mass Index (BMI) between 18.5 and 30 kg/m2.
  • Female subjects of non-childbearing potential may be enrolled in the study

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

    • has practiced adequate contraception for 30 days prior to first study product administration and
    • has a negative pregnancy test on the day of placebo administration/ vaccination, and
    • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study.

Exclusion Criteria:

  • Known history of HBV infection.
  • Previous vaccination against hepatitis B.
  • Positive for anti-hepatitis B surface (HBs) antibodies, anti-hepatitis B core (HBc) antibodies, HBsAg, HCV antibodies and/or HIV.
  • Any previous administration of vaccine components.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first study product administration, or planned use during the study period.
  • No significant dietary restrictions or life-threatening food allergies.
  • Regular use of non steroidal anti-inflammatory drugs within 1 month prior to first study product administration.
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first study product administration. Inhaled and topical steroids are allowed.
  • Planned administration / administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study product administration and during the entire study period (both Steps), with the exception of the influenza vaccine (pandemic or seasonal) which can be administered > 21 days preceding or > 21 days following each placebo/vaccine administration.
  • Administration of immunoglobulins and/or any blood products within the last 3 months preceding the first study product administration or planned administration during the study period.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV based on screening evaluations and on medical history and physical examination.
  • History of or current bleeding or coagulation disorder.
  • Any known or clinical signs of anaemia or any clinical condition (including vascular disorder) that would preclude frequent blood drawings.
  • Poor venous access as assessed at screening by the investigator.
  • Blood loss, including blood donation, of more than 300 mL within 90 days before the first study product administration.
  • History of or current autoimmune or other immune-mediated disease.
  • Any haematological or biochemical level out of normal range before entering into the study, as follows:

    • Haemoglobin level < lower normal limit (LNL).
    • Platelet counts out of normal range.
    • Alanine aminotransferase [ALT] > upper normal limit (UNL).
    • Aspartate aminotransferase [AST] > UNL.
    • Creatinine > UNL.
    • c-reactive protein [CRP] > UNL.
    • Creatine phosphokinase [CPK] > UNL without any plausible explanation for this abnormality (such as sport activity).

In case of haematological and/or biochemical value out of range for parameters mentioned here above, one re-testing of out of range value may be performed.

  • Any acute or chronic, clinically significant disease, as determined by medical history, physical examination or laboratory screening tests.
  • Known or suspected reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • Acute disease and/or fever at the time of enrolment.

    • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
    • Fever is defined as temperature ≥ 37.5°C for oral route.
  • Pregnant or lactating female.
  • Recent history of chronic alcohol consumption and/or drug abuse.
  • Other conditions that the principal investigator judges may interfere with study findings.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01777295

Locations
Belgium
GSK Investigational Site
Antwerpen, Belgium, 2060
Sponsors and Collaborators
GlaxoSmithKline
Public Private Partnership with Institute for Medical Immunology (Universite Libre de Bruxelles)
Region Wallonne
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01777295     History of Changes
Other Study ID Numbers: 116640, 2012-001344-22
Study First Received: January 24, 2013
Last Updated: March 27, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by GlaxoSmithKline:
Adults
Reactogenicity
Naive
Immune responses
Read-outs
Hepatitis B
Healthy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on July 28, 2014