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

Study Overview
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Brief Summary
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This study is conducted to assess the 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.

Official Title
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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

Conditions
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Hepatitis B

Intervention / Treatment
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* 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 vaccine adjuvanted with GSK's AS37 adjuvant system formulation 1
* Biological: GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HBs-alum Group<br>Participants receive three doses of GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide, one each at Day 1, Day 31 and Day 181. | Combination Product: GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide<br>* 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.<br>* Other names: Engerix-B;|
| Experimental: HBs-AS03 Group<br>Participants receive two doses of GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03, adjuvant system, one each at Day 1 and Day 31. | Biological: GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant system<br>* 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.<br>|
| Experimental: HBs-AS04 Group<br>Participants receive two doses of GSK's Hepatitis B vaccine adjuvanted with GSK's AS04, adjuvant system, one each at Day 1 and Day 31. | Biological: GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant system<br>* 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.<br>* Other names: Fendrix;|
| Experimental: HBs-AS37_formulation 1 Group<br>Participants receive two doses of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 1, one each at Day 1 and Day 31. | Biological: GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 1<br>* Two doses of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 1 administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.<br>|
| Experimental: HBs-AS37_formulation 2 Group<br>Participants receive two doses of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 2, one each at Day 1 and Day 31. | Biological: GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 2<br>* Two doses of GSK's HBsAg vaccine adjuvanted with GSK's AS37 adjuvant system formulation 2 administered intramuscularly in the non-dominant arm, one each at Day 1 and Day 31.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with solicited administration site events | The solicited administration site events are pain, redness and swelling. | Within 14 days after Dose 1 administration (Dose 1 administered at Day 1) | 
| Percentage of participants with solicited administration site events | The solicited administration site events are pain, redness and swelling. | Within 14 days after Dose 2 administration (Dose 2 administered at Day 31) | 
| Percentage of participants with solicited systemic events | The solicited systemic events are fever, fatigue, myalgia, arthralgia, headache, chills, malaise, loss of appetite, nausea, vomiting, diarrhoea. The preferred location for measuring temperature is the oral cavity. Fever is defined as temperature equal to or above (≥) 38.0 degree Celsius (°C)/ 100.4°F, regardless the location of measurement. | Within 14 days after Dose 1 administration (Dose 1 administered at Day 1) | 
| Percentage of participants with solicited systemic events | The solicited systemic events are fever, fatigue, myalgia, arthralgia, headache, chills, malaise, loss of appetite, nausea, vomiting, diarrhoea. The preferred location for measuring temperature is the oral cavity. Fever is defined as temperature equal to or above (≥) 38.0 degree Celsius (°C)/ 100.4°F, regardless the location of measurement. | Within 14 days after Dose 2 administration (Dose 2 administered at Day 31) | 
| Duration of solicited administration site events | Duration is defined as the number of days with solicited administration site events. | Within 14 days after Dose 1 administration (Dose 1 administered at Day 1) | 
| Duration of solicited administration site events | Duration is defined as the number of days with solicited administration site events. | Within 14 days after Dose 2 administration (Dose 2 administered at Day 31) | 
| Duration of solicited systemic events | Duration is defined as the number of days with solicited systemic events. | Within 14 days after Dose 1 administration (Dose 1 administered at Day 1) | 
| Duration of solicited systemic events | Duration is defined as the number of days with solicited systemic events. | Within 14 days after Dose 2 administration (Dose 2 administered at Day 31) | 
| Percentage of participants with any unsolicited adverse events (AEs) | 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. | Within 31 days after Dose 1 administration (Dose 1 administered at Day 1) | 
| Percentage of participants with any unsolicited adverse events (AEs) | 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. | Within 31 days after Dose 2 administration (Dose 2 administered at Day 31) | 
| Percentage 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. | Throughout the entire study period (from Day 1 to Day 361) | 
| Percentage 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. | Throughout the entire study period (from Day 1 to Day 361) | 
| Percentage 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) | 
| Percentage 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. | Throughout the entire study period (from Day 1 to Day 361) | 
| Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 8 |  | At Day 8 | 
| Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 31 |  | At Day 31 | 
| Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 38 |  | At Day 38 | 
| Percentage of participants with changes from baseline (pre-vaccination, Day 1) in haematology and biochemistry parameters at Day 61 |  | At Day 61 | 
| Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 1 | In the absence of a diagnosis, abnormal laboratory findings assessments (haematology or biochemistry) or other abnormal results the investigator considers clinically significant will be recorded as an AE or SAE, if they meet the definition of an AE or SAE. | At Day 1 | 
| Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 8 |  | At Day 8 | 
| Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 31 |  | At Day 31 | 
| Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 38 |  | At Day 38 | 
| Percentage of participants with abnormal haematology and biochemistry laboratory parameter values at Day 61 |  | At Day 61 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HBs antibody concentrations | Anti-HBs antibody concentrations are expressed as geometric mean concentrations (GMCs). | At Day 1, Day 31, Day 61 and Day 361 | 
| Percentage of participants seroconverted for anti-HBs | A participant seroconverted for anti-HBs is defined as a participant with an anti-HBs antibody concentration higher than (>) 6.2 milli-international units per milliliter (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 higher > 10 mIU/mL. | At Day 31, Day 61 and Day 361 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Hepatitis B virus, Hepatitis B surface antigen, Aluminum hydroxide, Adjuvant System, Safety, Immunogenicity