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

GlaxoSmithKline122 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

122

Conditions

Hepatitis B

Interventions

GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxideCOMBINATION_PRODUCT

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.

GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant systemBIOLOGICAL

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.

GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant systemBIOLOGICAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (5)

GSK Investigational Site

Leuven, Belgium

GSK Investigational Site

Cologne, Germany

GSK Investigational Site

Hamburg, Germany

GSK Investigational Site

Magdeburg, Germany

GSK Investigational Site

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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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.

GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37B adjuvant system (50 μg)BIOLOGICAL

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.

GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37A adjuvant system (100 μg)BIOLOGICAL

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.

Cambridge, United Kingdom

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: At Day 8

Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 31

Time frame: At Day 31

Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 38

Time frame: At Day 38

Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 61

Time frame: At Day 61

Secondary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: At Day 31, Day 61 and Day 361