Last updated: 07/17/2024 15:20:23

Study to compare the efficacy of GSK Biologicals’ adjuvants in combination with the antigen of the Hepatitis B vaccine

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GSK study ID
112115
See study documents
Clinicaltrials.gov ID
NCT00805389
See results summary
EudraCT ID
2008-004455-29
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Comparison of the immunogenicity and safety of various investigational and licensed formulations of Hepatitis B surface antigen (HBsAg) vaccines.
Trial description: The aim of this Observer-blind study is to compare different Adjuvant Systems with the same, well-known antigen (HBsAg) already used in the GSK marketed vaccines against Hepatitis B (Engerix-BTM and FendrixTM), in order to better understand the immune response induced by each of the Adjuvant System.
This Protocol Posting has been updated following Protocol amendment 6, October 2009. The section impacted is Eligibility Criteria
Primary purpose:
Prevention
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of Hepatitis B (HB)-specific Cluster of Differentiation 4 (CD4+) T cells .

Timeframe: At Day 44

Secondary outcomes:

Number of Hepatitis B (HB)-specific Cluster of Differentiation 4 (CD4+) T cells

Timeframe: At Days 0, 14, 30 and 60

Number of Hepatitis B (HB) - specific Cluster of Differentiation 8 (CD8+) T cells.

Timeframe: At Days 0, 14, 30, 44, and 60

Number of HB specific CD4+ T cells .

Timeframe: At Days 0, 180 and 360

Number of HB - specific CD8+ T cells.

Timeframe: At Days 0, 180 and 360

Number of HB - specific CD4+ T cells.

Timeframe: At Days 0, 360 and 374

Number of HB - specific CD8+ T cells

Timeframe: At Days 0, 360 and 374

Number of HB - specific CD4+ T cells

Timeframe: At Days 0, 14, 30, 33, 37, 44 and 60

Number of HB - specific CD8+ T cells

Timeframe: At Days 0, 14, 30, 44, 60 and 180

Number of Hepatitis B (HB)-specific Cluster of Differentiation 4 (CD4+) T cells expressing T helper cell type 1 response/T helper cell type 2 response (Th1/Th2) cytokine profile

Timeframe: At Days 0, 14, 30, 44 and 60

Number of HB specific Cluster of Differentiation 4 (CD4+) T cells expressing Th1/Th2 cytokine profile

Timeframe: At Days 0 and 180

Anti-Hepatitis B (anti-HB) antibody concentrations in serum, as measured by Chemi Luminescence Immuno Assay (CLIA)

Timeframe: At Days 0, 30, 44, and 60

Anti-HB antibody concentrations in serum, as measured by Chemi Luminescence Immuno Assay (CLIA)

Timeframe: At Days 0, 180 and 360

Anti-HB antibody concentrations in serum, as measured by CLIA

Timeframe: At Days 0, 374 and 390

Number of Hepatitis B (HB)-specific memory B cells

Timeframe: At Days 0, 30, 37, 44 and 60.

Number of HB-specific memory B cells

Timeframe: At Days 180 and 360

Concentrations of the Interferon-gamma (IFN-g), Interleukin (IL)-1beta, IL-5, IL-6, IL-10, Tumor Necrosis Factor-alpha, IFN-g-inducible protein-10 and monocyte chemotactic protein-1 cytokines in serum

Timeframe: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30,30+ (Day 30 + 3 to 6 hours), 31, 33 and 37.

Normalized levels of white blood cells (WBC) and creatine phosphokinases (CPK)

Timeframe: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60.

Normalized levels of C-reactive protein (CRP)

Timeframe: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33 and 37.

Normalized levels of WBC and of CPK

Timeframe: At Days 0, 30, 37 and 60.

Normalized levels of CRP

Timeframe: At Days 0, 30 and 37.

Levels of white blood cells, neutrophils, lymphocytes, monocytes, eosinophils and basophils

Timeframe: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60.

Levels of WBC, NEU, LYM, MON, EOS and BAS

Timeframe: At Days 0, 30, 37 and 60.

Normalized levels of red blood cells and platelets

Timeframe: At Days 0, 30, 37 and 60.

Normalized levels of haemoglobin, alanine aminotransferase and aspartate aminotransferase

Timeframe: At Days 0, 30, 37 and 60.

Normalized levels of serum creatinine, urea and lactate dehydrogenase

Timeframe: At Days 0, 30, 37 and 60.

Number of subjects with normal and abnormal levels of white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, C-reactive protein, and creatine phosphokinase.

Timeframe: At Day 0 and up to Day 60.

Number of subjects with normal and abnormal levels of WBC, NEU, LYM, MON, EOS, BAS, CRP, and CPK.

Timeframe: At Day 0 and up to Day 60.

Number of subjects presenting normal and abnormal levels of white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, C-reactive protein, and creatine phosphokinase.

Timeframe: Post vaccination (up to Day 360)

Number of subjects having normal and abnormal levels of WBC, NEU, LYM, MON, EOS, BAS, CRP, and CPK.

Timeframe: At Days 360 and 390.

Number of subjects with normal and abnormal levels of red blood cells, platelets, haemoglobin, alanine aminotransferase, aspartate aminotransferase, serum creatinine, urea and lactate dehydrogenase

Timeframe: At Day 0 and up to Day 60.

Number of subjects with normal and abnormal levels of RBC, PLA, HGB, ALT, AST, S-CREA, urea and LDH

Timeframe: post vaccination (up to Day 360).

Number of subjects presenting normal and abnormal levels of red blood cells, platelets, haemoglobin, alanine aminotransferase, aspartate aminotransferase, serum creatinine, urea and lactate dehydrogenase

Timeframe: At Days 360 and 390.

Number of subjects reporting any, grade 3 and related solicited local symptoms following primary vaccination.

Timeframe: Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccines.

Number of subjects reporting any, grade 3 and related solicited general symptoms following primary vaccination.

Timeframe: Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine.

Number of subjects reporting any, grade 3 and related solicited local symptoms following booster vaccination.

Timeframe: Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens

Number of subjects reporting any, grade 3 and related solicited general symptoms following booster vaccination.

Timeframe: Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens

Number of subjects reporting any, Grade 3 and/or related unsolicited adverse events (AEs) following primary vaccination

Timeframe: Within the 31-day (Days 0-30) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine

Number of subjects reporting any, Grade 3 and/or related unsolicited adverse events (AEs) following booster vaccination

Timeframe: Within the 31-day (Days 0-30) follow up period following booster vaccination with HBsAg antigens

Number of subjects reporting any and related adverse events of specific interest (AESIs)

Timeframe: During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2.

Number of subjects reporting any serious adverse events (SAEs) and SAEs related to study vaccination

Timeframe: During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2.

Levels of messenger ribonucleic acid (mRNA) as measured by quantitative polymerase chain reaction (qPCR)

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

mRNA levels as measured by qPCR

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

mRNA levels as measured by quantitative polymerase chain reaction (qPCR)

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

Messenger ribonucleic acid (mRNA) levels as measured by quantitative polymerase chain reaction (qPCR)

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

Levels of mRNA as measured by qPCR

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

Levels of messenger ribonucleic acid (mRNA) as measured by qPCR

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

Levels of mRNA as measured by quantitative polymerase chain reaction (qPCR)

Timeframe: At Days 0, 1, 14, 30, 31, 33 and 37

Interventions:
  • Biological/vaccine: Engerix-B™
  • Biological/vaccine: Fendrix™
  • Biological/vaccine: GSK Biologicals’ Hepatitis B vaccines (GSK223192A)
  • Biological/vaccine: HBsAg (Booster injection)
    • Enrollment:
    713
    Primary completion date:
    2010-29-09
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Burny W et al. (2017) Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans. Front Immunol. 8:943.
    Leroux-Roels G et al. (2016) Impact of adjuvants on CD4+ T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial. Clin Immunol.169:16-27.
    Burny W et al. (2019) Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans. Vaccine. 37(14):2004-2015. doi: 10.1016/j.vaccine.2019.02.015.
    Medical condition
    Hepatitis B
    Product
    GSK2231392A, SB208129, SKF103860
    Collaborators
    Not applicable
    Study date(s)
    December 2008 to July 2011
    Type
    Interventional
    Phase
    1/2

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 45 years
    Accepts healthy volunteers
    Yes
    • Inclusion Criteria:
    • All subjects must satisfy the following criteria at study entry :
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Inclusion Criteria: All subjects must satisfy the following criteria at study entry :
    • Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
    • A male or female between, and including, 18 and 45 years at the time of the first vaccination.
    • Written informed consent obtained from the subject.
    • Healthy subjects as established by medical history, clinical examination and clinical laboratory assessment before entering into the study.
    • If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series. Exclusion criteria: The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
    • Previous vaccination against Hepatitis B.
    • Positive for anti-HBs antibodies, antiHBc antibodies, HBsAg, HCV antibodies and/or HIV.
    • Any previous administration of specific adjuvant components.
    • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
    • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
    • Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the influenza vaccine (pandemic or seasonal) which can be administered > 21 days preceding or > 21 days following each primary vaccine dose (Doses 1 and 2) AND > 7 days preceding or > 7 days following the booster dose.
    • Administration of immunoglobulins and/or any blood products within the last 3 months.
    • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
    • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
    • Current serious neurologic or mental disease.
    • Any past or current malignancies and lymphoproliferative disorders.
    • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal functional abnormality, autoimmune disease or anemia, as determined by physical examination or laboratory screening tests at the discretion of the investigator.
    • Acute disease at the time of enrolment.
    • Pregnant or lactating female.
    • History of chronic alcohol consumption and/or drug abuse.
    • Other conditions that the principal investigator judges may interfere with study findings.

    Trial location(s)

    Location
    Status
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    Location
    GSK Investigational Site
    Haag, Bayern, Germany, 83527
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Berlin, Berlin, Germany, 12627
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Gent, Belgium, 9000
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Berlin, Berlin, Germany, 13125
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Tuebingen, Baden-Wuerttemberg, Germany, 72074
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Wuerzburg, Bayern, Germany, 97070
    Status
    Study Complete
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    Showing 1 - 6 of 15 Results

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2010-29-09
    Actual study completion date
    2011-14-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

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    Additional information
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