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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 5
- 主要终点
- Number of Participants With Solicited Administration Site Adverse Events (AEs) After Dose 1
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 AS
- •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.
研究组 & 干预措施
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.
干预措施: GSK's Hepatitis B vaccine adjuvanted with aluminum hydroxide (Combination Product)
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.
干预措施: GSK's HBsAg candidate vaccine adjuvanted with GSK's AS03 adjuvant system (Biological)
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.
干预措施: GSK's Hepatitis B vaccine adjuvanted with GSK's AS04 adjuvant system (Biological)
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.
干预措施: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37B adjuvant system (50 μg) (Biological)
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.
干预措施: GSK's HBsAg (20 μg) vaccine adjuvanted with GSK's AS37A adjuvant system (100 μg) (Biological)
结局指标
主要结局
Number of Participants With Solicited Administration Site Adverse Events (AEs) After Dose 1
时间窗: Day 1 (day of administration) to Day 14
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.
Number of Participants With Solicited Administration Site AEs After Dose 2
时间窗: Day 31 (day of administration) to Day 45
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.
Number of Participants With Solicited Systemic AEs After Dose 1
时间窗: Day 1 (day of administration) to Day 14
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.
Number of Participants With Solicited Systemic AEs After Dose 2
时间窗: Day 31 (day of administration) to Day 45
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.
Duration in Days of Solicited Administration Site AEs After Dose 1
时间窗: Day 1 (day of administration) to Day 14
Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.
Duration in Days of Solicited Administration Site AEs After Dose 2
时间窗: Day 31 (day of administration) to Day 45
Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.
Duration in Days of Solicited Systemic AEs After Dose 1
时间窗: Day 1 (day of administration) to Day 14
Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.
Duration in Days of Solicited Systemic AEs After Dose 2
时间窗: Day 31 (day of administration) to Day 45
Duration is the number of days in which a participant experienced the symptom within the 14-day solicited follow-up period.
Number of Participants With Any Unsolicited AEs After Dose 1
时间窗: Day 1 (day of administration) to Day 31
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.
Number of Participants With Any Unsolicited AEs After Dose 2
时间窗: Day 31 (day of administration) to Day 61
Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants With Serious AEs (SAEs)
时间窗: Throughout the entire study period (from Day 1 to Day 361)
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.
Number of Participants With Medically Attended AEs (MAEs)
时间窗: Throughout the entire study period (from Day 1 to Day 361)
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.
Number of Participants With AEs Leading to Study Withdrawal
时间窗: Throughout the entire study period (from Day 1 to Day 361)
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.
Number of Participants With Potential Mediated Immune Diseases (pIMDs)
时间窗: Throughout the entire study period (from Day 1 to Day 361)
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.
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 1
时间窗: At Day 8 (relative to baseline [pre-vaccination Day 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).
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 1
时间窗: At Day 31 (compared with baseline [prevaccination, 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.
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 2
时间窗: At Day 38 (compared with baseline [pre-vaccination, 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.
Mean Percent Change From Baseline (Pre-vaccination, Day 1) in Hematology and Biochemistry Parameters Post-dose 2
时间窗: At Day 61 (compared with baseline [pre-vaccination, 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.
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 1
时间窗: At Day 1 (baseline)
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.
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 8
时间窗: 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.
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 31
时间窗: 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.
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 38
时间窗: 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.
Number of Participants With Abnormal Hematology and Biochemistry Laboratory Parameter Values at Day 61
时间窗: 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.
次要结局
- Geometric Mean Concentration (GMC) of Anti-HBs Antibody Concentrations(At Day 1, Day 31, Day 61 and Day 361)
- Percentage of Participants Who Seroconverted for Anti-HBs(At Day 31, Day 61 and Day 361)
- Percentage of Participants Seroprotected for Anti-HBs(At Day 31, Day 61 and Day 361)