Study to Compare the Efficacy of GSK Biologicals' Adjuvants in Combination With the Antigen of the Hepatitis B Vaccine

NCT00805389 | Completed Phase 2 Results

• 1 other identifier: 112115
• Study Type: interventional
• Target: 713
• Locations: 2 countries
• Sites: 14

Brief Summary

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

Conditions

Hepatitis B

Keywords

Adjuvant Systems; Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells .

  The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD40L), Interleukin (IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs). Results for the Day 44 time point are the primary results among the outcome measure results presented.

  At Day 44

Secondary Outcomes (47)

• Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells

  At Days 0, 14, 30 and 60

• Number of Hepatitis B (HB) - Specific Cluster of Differentiation 8 (CD8+) T Cells.

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

• Number of HB Specific CD4+ T Cells .

  At Days 0, 180 and 360

• Number of HB - Specific CD8+ T Cells.

  At Days 0, 180 and 360

• Number of HB - Specific CD4+ T Cells.

  At Days 0, 360 and 374

Study Arms (5)

GSK223192A 1 Group

EXPERIMENTAL

Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 1, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A); Biological: HBsAg (Booster injection)

GSK223192A 2 Group

EXPERIMENTAL

Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 2, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A); Biological: HBsAg (Booster injection)

GSK223192A 3 Group

EXPERIMENTAL

Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 3, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A); Biological: HBsAg (Booster injection)

Fendrix Group

EXPERIMENTAL

Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Fendrix™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Fendrix™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: Fendrix™; Biological: HBsAg (Booster injection)

Engerix-B Group

ACTIVE COMPARATOR

Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Engerix-B™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Engerix-B™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.

Biological: Engerix-B™; Biological: HBsAg (Booster injection)

Interventions

Engerix-B™ BIOLOGICAL

2 doses intramuscular injections

Engerix-B Group

Fendrix™ BIOLOGICAL

2 doses intramuscular injections

Fendrix Group

GSK Biologicals' Hepatitis B vaccines (GSK223192A) BIOLOGICAL

2 doses intramuscular injections 3 different formulations of (GSK223192A), each administered to 1 group

GSK223192A 1 Group; GSK223192A 2 Group; GSK223192A 3 Group

HBsAg (Booster injection) BIOLOGICAL

Single dose intramuscular injection

Engerix-B Group; Fendrix Group; GSK223192A 1 Group; GSK223192A 2 Group; GSK223192A 3 Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

La Louvière, 7100, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72074, Germany

Location

GSK Investigational Site

Haag, Bavaria, 83527, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80636, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81241, Germany

Location

GSK Investigational Site

Regensburg, Bavaria, 93053, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Berlin, 12627, Germany

Location

GSK Investigational Site

Berlin, 13125, Germany

Location

GSK Investigational Site

Hamburg, 20253, Germany

Location

Related Publications (6)

• Tasdighian S, Bechtold V, Essaghir A, Saeys Y, Burny W. An innate immune signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time. Front Immunol. 2024 Aug 14;15:1412732. doi: 10.3389/fimmu.2024.1412732. eCollection 2024.

  PMID: 39206189 DERIVED

• Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.

  PMID: 33493551 DERIVED

• De Mot L, Bechtold V, Bol V, Callegaro A, Coccia M, Essaghir A, Hasdemir D, Ulloa-Montoya F, Siena E, Smilde A, van den Berg RA, Didierlaurent AM, Burny W, van der Most RG. Transcriptional profiles of adjuvanted hepatitis B vaccines display variable interindividual homogeneity but a shared core signature. Sci Transl Med. 2020 Nov 11;12(569):eaay8618. doi: 10.1126/scitranslmed.aay8618.

  PMID: 33177181 DERIVED

• Hasdemir D, van den Berg RA, van Kampen A, Smilde AK. Modeling adaptive response profiles in a vaccine clinical trial. BMC Med Res Methodol. 2020 Jul 16;20(1):191. doi: 10.1186/s12874-020-01070-3.

  PMID: 32677968 DERIVED

• Burny W, Marchant A, Herve C, Callegaro A, Caubet M, Fissette L, Gheyle L, Legrand C, Ndour C, Tavares Da Silva F, van der Most R, Willems F, Didierlaurent AM, Yarzabal J; ECR-008 study group. Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans. Vaccine. 2019 Mar 28;37(14):2004-2015. doi: 10.1016/j.vaccine.2019.02.015. Epub 2019 Mar 5.

  PMID: 30850240 DERIVED

• Burny W, Callegaro A, Bechtold V, Clement F, Delhaye S, Fissette L, Janssens M, Leroux-Roels G, Marchant A, van den Berg RA, Garcon N, van der Most R, Didierlaurent AM; ECR-002 Study Group. Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans. Front Immunol. 2017 Aug 14;8:943. doi: 10.3389/fimmu.2017.00943. eCollection 2017.

  PMID: 28855902 DERIVED

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Hepatitis B

Interventions

Engerix-B; Fendrix; Hepatitis B Surface Antigens; Immunization, Secondary

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Hepatitis B Antigens; Hepatitis Antigens; Antigens, Viral; Viral Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2008
• First Posted: December 9, 2008
• Study Start: December 15, 2008
• Primary Completion: September 29, 2010
• Study Completion: July 14, 2011
• Last Updated: August 20, 2018
• Results First Posted: January 25, 2013

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (4); DE (10)