Clinical trial NCT00805389: Study to Compare the Efficacy of GSK Biologicals' Adjuvants in Combination With the Antigen of the Hepatitis B Vaccine
Official title: Comparison of the Immunogenicity and Safety of Various Investigational and Licensed Formulations of Hepatitis B Surface Antigen (HBsAg) Vaccines.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B
Keywords: Adjuvant Systems
Hepatitis B
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-12-09
Enrollment: 713
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


Eligibility 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.

Primary outcomes:
measure: Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells .
timeFrame: At Day 44
Secondary outcomes:
measure: Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells
timeFrame: At Days 0, 14, 30 and 60
measure: Number of Hepatitis B (HB) - Specific Cluster of Differentiation 8 (CD8+) T Cells.
timeFrame: At Days 0, 14, 30, 44, and 60
measure: Number of HB Specific CD4+ T Cells .
timeFrame: At Days 0, 180 and 360
measure: Number of HB - Specific CD8+ T Cells.
timeFrame: At Days 0, 180 and 360
measure: Number of HB - Specific CD4+ T Cells.
timeFrame: At Days 0, 360 and 374
measure: Number of HB - Specific CD8+ T Cells
timeFrame: At Days 0, 360 and 374
measure: Number of HB - Specific CD4+ T Cells
timeFrame: At Days 0, 14, 30, 33, 37, 44 and 60
measure: Number of HB - Specific CD8+ T Cells
timeFrame: At Days 0, 14, 30, 44, 60 and 180
measure: 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
measure: Number of HB Specific Cluster of Differentiation 4 (CD4+) T Cells Expressing Th1/Th2 Cytokine Profile
timeFrame: At Days 0 and 180
measure: 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
measure: Anti-HB Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA)
timeFrame: At Days 0, 180 and 360
measure: Anti-HB Antibody Concentrations in Serum, as Measured by CLIA
timeFrame: At Days 0, 374 and 390
measure: Number of Hepatitis B (HB)-Specific Memory B Cells
timeFrame: At Days 0, 30, 37, 44 and 60.
measure: Number of HB-specific Memory B Cells
timeFrame: At Days 180 and 360
measure: 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.
measure: 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.
measure: 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.
measure: Normalized Levels of WBC and of CPK
timeFrame: At Days 0, 30, 37 and 60.
measure: Normalized Levels of CRP
timeFrame: At Days 0, 30 and 37.
measure: 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.
measure: Levels of WBC, NEU, LYM, MON, EOS and BAS
timeFrame: At Days 0, 30, 37 and 60.
measure: Normalized Levels of Red Blood Cells and Platelets
timeFrame: At Days 0, 30, 37 and 60.
measure: Normalized Levels of Haemoglobin, Alanine Aminotransferase and Aspartate Aminotransferase
timeFrame: At Days 0, 30, 37 and 60.
measure: Normalized Levels of Serum Creatinine, Urea and Lactate Dehydrogenase
timeFrame: At Days 0, 30, 37 and 60.
measure: 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.
measure: 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.
measure: 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)
measure: Number of Subjects Having Normal and Abnormal Levels of WBC, NEU, LYM, MON, EOS, BAS, CRP, and CPK.
timeFrame: At Days 360 and 390.
measure: 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.
measure: 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).
measure: 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.
measure: 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.
measure: 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.
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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.
measure: 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.
measure: 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
measure: mRNA Levels as Measured by qPCR
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
measure: mRNA Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR)
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
measure: Messenger Ribonucleic Acid (mRNA) Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR)
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
measure: Levels of mRNA as Measured by qPCR
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
measure: Levels of Messenger Ribonucleic Acid (mRNA) as Measured by qPCR
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
measure: Levels of mRNA as Measured by Quantitative Polymerase Chain Reaction (qPCR)
timeFrame: At Days 0, 1, 14, 30, 31, 33 and 37
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: La Louvière
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Haag
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Regensburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.