A Study on the Safety and Immune Response of AS37 Together With Hepatitis B Antigen in Adults Aged 18-45 Years

A Phase I/IIa, Open-label, Randomised, Controlled, Multi-country, Dose-escalation Study to Assess the Safety and Immunogenicity of AS37 in Combination With the Hepatitis B Surface Antigen (HBsAg), According to a 0-1 Month Schedule, in Healthy, HBs naïve, Adults Aged 18-45 Years

This study is conducted to assess safety and immunogenicity of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system in healthy, HBs naïve, adults aged 18-45 years and to differentiate GSK's AS37 adjuvant system from other approved adjuvant systems and from an aluminum-based adjuvant.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Combination product: GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide; Biological: GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant system; Biological: GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant system; Biological: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37B adjuvant system (50 μg); Biological: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37A adjuvant system (100 μg)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • GSK Investigational Site
• Germany
  • Cologne, Germany, 51069
    • GSK Investigational Site
  • Hamburg, Germany, 22143
    • GSK Investigational Site
  • Magdeburg, Germany, 39120
    • GSK Investigational Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who the investigator believe can and will comply with the requirements of the protocol.
• Written informed consent obtained from the participant prior to performance of any study-specific procedure.
• Healthy participants as established by medical history, clinical examination and clinical laboratory assessment before entering the study.
• A male or female between, and including, 18 and 45 years at the time of the first study intervention administration.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.

• Female participants of childbearing potential may be enrolled in the study, if the participant:

  • has practiced adequate contraception for 1 month prior to study intervention administration, and
  • has a negative pregnancy test on the day of study intervention administration, and
  • has agreed to continue adequate contraception during the entire treatment period and for at least 3 months after completion of the study intervention administration series.
  • blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the investigator to confirm non-reproductive potential according to local laboratory reference range.

Exclusion Criteria:

Medical conditions

• Previous vaccination against Hepatitis B.
• Positive for anti-HBs antibodies or anti-HBc antibodies or HBsAg.
• Any previous administration of monophosphoryl lipid (MPL) and/or AS37.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Any confirmed or suspected autoimmune disease.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• Recurrent history or uncontrolled neurological disorders or seizures.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

• Any clinically significant* haematological and/or biochemical laboratory abnormality.

  *The investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.

• Any past or current malignancies and lymphoproliferative disorders.

Prior/Concomitant therapy

• Use of any investigational or non-registered product (drug or vaccine) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) or their planned use during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after each dose of study intervention(s) administration with the exception of influenza vaccine (pandemic or seasonal).

• A vaccine not foreseen by the study protocol administered during the period starting at Visit 1 or 30 days before each dose and ending 30 days after the last dose of study intervention(s) administration*, with the exception of influenza vaccine (pandemic or seasonal).

  *In case emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by public health authorities outside the routine immunisation programme, the time period described above can be reduced if necessary for that vaccine, provided it is licensed/authorised and used according to its Product Information.

• Administration of long-acting immune-modifying drugs at any time during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months before the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention(s) or planned administration during the study period.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational intervention.

Other exclusions

• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of chronic alcohol consumption and/or drug abuse.
• Any study personnel or their immediate depandants, family, or household members.

Specific exclusion for MRI-assessable subgroup participants (post-randomization procedure)

• Presence of pacemakers, metal implants and/or prostheses.
• Claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HBs-alum Group; Participants received 3 doses of GSK's Hepatitis B (HBsAg) vaccine adjuvanted with aluminum hydroxide, at Day 1, Day 31 and Day 181.	Combination product: GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide; Three doses of GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide administered intramuscularly in the non-dominant arm, one each at Day 1, Day 31 and Day 181.; Other Names: Engerix-B
Experimental: HBs-AS03 Group; Participants received 2 doses of GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03, adjuvant system, at Day 1 and Day 31.	Biological: GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant system; Two doses of GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant system administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.
Experimental: HBs-AS04 Group; Participants received 2 doses of GSK's HBsAg vaccine adjuvanted with GSK's AS04, adjuvant system, at Day 1 and Day 31.	Biological: GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant system; Two doses of GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant system administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.; Other Names: Fendrix
Experimental: HBs-AS37B Group; Participants received 2 doses of GSK's HBsAg (20 µg) candidate vaccine adjuvanted with GSK's AS37B adjuvant system (50 µg), at Day 1 and Day 31.	Biological: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37B adjuvant system (50 μg); Two doses of GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37B adjuvant system (50 μg) administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.
Experimental: HBs-AS37A Group; Participants received 2 doses of GSK's HBsAg (20 µg) candidate vaccine adjuvanted with GSK's AS37A adjuvant system (100 µg), at Day 1 and Day 31.	Biological: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37A adjuvant system (100 μg); Two doses of GSK's HBsAg (20 μg )vaccine adjuvanted with GSK's AS37A adjuvant system (100 μg) administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Administration Site Adverse Events (AEs) After Dose 1	Assessed solicited administration site events after vaccination included erythema, pain, and swelling at the injection site. Any = occurrence of the event regardless of intensity grade.	Day 1 (day of administration) to Day 14
Number of Participants With Solicited Administration Site AEs After Dose 2	Assessed solicited administration site events after vaccination included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade.	Day 31 (day of administration) to Day 45
Number of Participants With Solicited Systemic AEs After Dose 1	Assessed solicited systemic events included fever (defined as temperature greater than or equal to (>=) 38.0°C regardless of the location of measurement), fatigue, myalgia, arthralgia, headache, chills, malaise, loss of appetite, nausea, vomiting, and diarrhea.	Day 1 (day of administration) to Day 14
Number of Participants With Solicited Systemic AEs After Dose 2	Assessed solicited systemic events included fever (defined as temperature >=38.0°C regardless of the location of measurement), fatigue, myalgia, arthralgia, headache, chills, malaise, loss of appetite, nausea, vomiting, and diarrhea.	Day 31 (day of administration) to Day 45
Duration in Days of Solicited Administration Site AEs After Dose 1	Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.	Day 1 (day of administration) to Day 14
Duration in Days of Solicited Administration Site AEs After Dose 2	Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.	Day 31 (day of administration) to Day 45
Duration in Days of Solicited Systemic AEs After Dose 1	Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.	Day 1 (day of administration) to Day 14
Duration in Days of Solicited Systemic AEs After Dose 2	Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.	Day 31 (day of administration) to Day 45
Number of Participants With Any Unsolicited AEs After Dose 1	An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.	Day 1 (day of administration) to Day 31
Number of Participants With Any Unsolicited AEs After Dose 2	Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.	Day 31 (day of administration) to Day 61
Number of Participants With Serious AEs (SAEs)	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or is an abnormal pregnancy outcome. Any = occurrence of the SAE regardless of intensity grade or relation to the study vaccination.	Throughout the entire study period (from Day 1 to Day 361)
Number of Participants With Medically Attended AEs (MAEs)	An MAE is any AE with medically attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any = occurrence of the MAE regardless of intensity grade or relation to the study vaccination.	Throughout the entire study period (from Day 1 to Day 361)
Number of Participants With AEs Leading to Study Withdrawal	An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact.	Throughout the entire study period (from Day 1 to Day 361)
Number of Participants With Potential Mediated Immune Diseases (pIMDs)	pIMDs are a subset of adverse events that include autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune aetiology. Any = occurrence of the pIMD regardless of intensity grade or relation to the study vaccination.	Throughout the entire study period (from Day 1 to Day 361)
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 1	In the analysis were included biochemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, white blood cells (WBC).	At Day 8 (relative to baseline [pre-vaccination Day 1])
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 1	In the analysis were included biochemistry parameters: ALT, AST, bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, WBC.	At Day 31 (compared with baseline [prevaccination, Day 1])
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 2	In the analysis were included biochemistry parameters: ALT, AST, bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, WBC.	At Day 38 (compared with baseline [pre-vaccination, Day 1])
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 2	In the analysis were included biochemistry parameters: ALT, AST, bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, WBC.	At Day 61 (compared with baseline [pre-vaccination, Day 1])
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 1	In the analysis were included biochemistry parameters: ALT, AST, bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, WBC. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 1 (baseline)
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 8	In the analysis were included biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, white blood cells (WBC).Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 31	In the analysis were included biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, white blood cells (WBC).Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 31
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 38	In the analysis were included biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, white blood cells (WBC).Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 38
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 61	In the analysis were included biochemistry parameters: alanine aminotransferase (ALT), aspartate transaminase (AST), bicarbonate, blood urea nitrogen, chloride, C reactive protein, creatinine, potassium, sodium; and hematology parameters: eosinophils, erythrocytes, hemoglobin, lymphocytes, platelets, monocytes, neutrophils, white blood cells (WBC).Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 61

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) of Anti-HBs Antibody Concentrations	Anti-HBs antibody concentration was measured as GMC and expressed in milli international units per milliliter (mIU/mL).	At Day 1, Day 31, Day 61 and Day 361
Percentage of Participants Who Seroconverted for Anti-HBs	A participant who seroconverted for anti-HBs is defined as a participant with an anti-HBs antibody concentration higher than (>) 6.2 mIU/mL.	At Day 31, Day 61 and Day 361
Percentage of Participants Seroprotected for Anti-HBs	A participant seroprotected for anti-HBs is defined as a participant with an anti-HBs antibody concentration >10 mIU/mL.	At Day 31, Day 61 and Day 361

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2022
• Primary Completion (Actual): November 29, 2024
• Study Completion (Actual): November 29, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Hepatitis B; Hepatitis B virus; Hepatitis B surface antigen; Aluminum hydroxide; Adjuvant System
• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Inorganic Chemicals; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Aluminum Compounds; Aluminum Hydroxide; Engerix-B; Fendrix
• Other Study ID Numbers: 215301; 2021-005629-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer tohttps://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No