A first-time-in Human (FTIH), Phase I/II, Randomized, Multi-centric, Single-blind, Controlled Dose-escalation Study to Evaluate the Reactogenicity, Safety, Immunogenicity and Efficacy of GSK Biologicals' HBV Viral Vector Vaccines Given in a Prime-boost Schedule With Sequential or Co-administration of Adjuvanted Proteins Therapeutic Vaccine (GSK3528869A) in Chronic Hepatitis B Patients (18-65 Years Old) Well Controlled Under Nucleo(s)Tide Analogue (NA) Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 236
- 试验地点
- 43
- 主要终点
- Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 1
研究概览
简要总结
A First-Time-In-Human study on GSK's therapeutic vaccines to evaluate the reactogenicity, safety, immunogenicity and efficacy on reduction of serum HBV surface antigen in HBV suppressed participants under nucleo(s)tide treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written informed consent obtained from the patient prior to performing any study specific procedure.
- •A male or female between, and including, 18 and 65 years of age at the time of the first vaccination.
- •Female patients of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, bilateral ovariectomy or post-menopause.
- •Female patients of childbearing potential may be enrolled in the study if the patient:
- •has practiced adequate contraception for 30 days prior to vaccination, and
- •has a negative pregnancy test at Screening, and
- •has agreed to continue adequate contraception from Screening until 12 weeks after completion of the vaccination series
- •Male patients:
- •with documented bilateral vasectomy and resultant azoospermia, bilateral orchiectomy or azoospermia, or
- •who agree to practice abstinence from penile-vaginal intercourse (when this is their preferred and usual lifestyle) or use condoms from Screening until 12 weeks after completion of the vaccination series.
- •Chronic Hepatitis B (CHB) patient, under and adherent to treatment with a nucleo(s)tide analogue with high barrier to resistance given as per approved label/dosage for at least 24 months.
- •Documented medical history of Hepatitis B Virus e Antigen (HBeAg)-negative CHB prior to onset of NA therapy (applicable to all patients in Step A and Step B and to some patients in Step C) or documented medical history of HBeAg-negative CHB over a period of at least 24 months prior screening (applicable to some patients in Step C only).
- •Documented HBV viral suppression as per local clinical diagnosis within the previous 24 months AND at Screening test HBV DNA < 10 IU/mL. If no results are available, two Screening tests need to be performed at least 2 weeks apart. Small fluctuations of HBV DNA (≤ 10 x LLOQ; LLOQ defined by laboratory that performed testing) are allowed provided HBV DNA is < 10 IU/mL at Screening and was clearly not rising during the previous 24 months.
- •Documented normal level of ALT as per local clinical diagnosis within the previous 24 months AND at Screening test ALT < 48U/L. Small fluctuations of ALT (≤ 1.5 X ULN) are allowed provided ALT< 48 U/L at Screening. If no results are available, two Screening tests need to be performed at least 2 weeks apart. ULN are to be defined according to local laboratory reference range.
- •No clinical diagnosis of cirrhosis (e.g. F4 by METAVIR scoring system or ≥ 6 by Ishak scoring system or FibroScan TE score > 12.5 kPa) within the previous 24 months.
- •FibroScan Transient Elastography (TE) score < 9.6 kPa and FibroTest score < 0.59 at Screening. A patient with one of these parameters out of range, but having the liver biopsy within 12 months before screening that showed F0-2 by METAVIR scoring system or stage 0-4 by Ishak scoring system, can be included.
- •HBsAg concentration > 50 IU/mL and anti-HBs negative at Screening.
- •Anti-HBc positive at Screening.
- •HBeAg-negative at Screening.
排除标准
- •Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period.
- •Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
- •Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 10 mg/day or equivalent. Inhaled and topical steroids are allowed.
- •Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.
- •Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which, in the opinion of the investigator, may have activity against HBV within the previous 6 months prior to randomization into this study. Antiviral treatment/prevention for influenza or herpes simplex virus is allowed.
- •Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months except for adenovirus/adenovector-based COVID-19 vaccines that could be administered up to 30 days prior to the first study vaccine dose (applicable for all patients except for the patients in France) OR Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months (applicable for the patients in France only).
- •Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 14 days before each dose and ending 30 days after each dose of vaccines, with the exception of influenza vaccine that may be given at any time except within a 7-day period before or after each vaccine dose and COVID-19 vaccine that may be given at any time except within a 30-day period before or after each vaccine dose apart from COVID-19 mRNA based-vaccines that may be administered any time except for the period of 14 days before and 30 days after each study vaccine dose. Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 days before or after each study vaccine dose should be followed.
- •Treatment with nephrotoxic drugs or competitors of renal excretion within 2 months prior to Screening or the expectation that patient will receive any of these during the course of the study. TAF/TDF given as NA therapy is allowed.
- •Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational vaccine/product.
- •Medical history of cirrhosis or hepatic decompensation.
- •Planned for liver transplantation or previous liver transplantation.
- •Personal or family (first degree) history of autoimmune disease.
- •Family history of congenital or hereditary immunodeficiency.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
- •Evidence of Hepatitis C Virus and hepatitis D Virus infection.
- •Suspicion of or confirmed Hepatocellular Carcinoma or any other liver cancer in medical history or at Screening:
- •Suspicious foci at liver imaging exam
- •Elevated α-fetoprotein > 50 ng/mL.
- •Documented evidence of other currently active cause of hepatitis.
- •Hematology and biochemistry parameters outside normal clinical range at Screening:
- •Biochemistry:
- •Glomerular filtration rate < 60 mL/min
- •Bilirubin > 27.5 µmol/L unless *or the diagnosis of Gilbert Syndrome has been established and confirmed by the Investigator
- •GGT > 65 U/L (males) or > 45 U/L (females)*
- •ALT > 48 U/L
- •AST > 42 U/L*
- •ALP > 125 U/L*
- •Hematology:
- •Hemoglobin < 12.0 g/dL (females) or < 13.5 g/dL (males)*
- •Red blood cell count < 3.9 x 10^6 cells/mm^3 (females) or < 4.4 x 10^6 cells/mm^3 (males)*
- •White blood cell count < 3,500 cells/mm^3 or > 12,000 cells/mm^3*
- •Platelets < 140,000 cells/mm^3
- •INR > 1.32 (i.e. 1.1 x ULN) *unless it is considered as clinically not significant by the Investigator
- •Known diabetes Type I.
- •Body Mass Index > 35 kg/m^2 at Screening.
- •Any serious or active medical or psychiatric illnesses other than chronic hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
- •History of or current drug abuse and/or excess of alcohol consumption as defined per local guidelines.
- •HIV-positive patient.
- •Pregnant or lactating female.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions in the period starting from the Screening Visit up to 12 weeks post-last vaccination visit.
- •Fever and or acute minor illness may be enrolled for Screening at the discretion of the investigator, provided that the condition is resolved at the time of vaccination.
研究组 & 干预措施
Step A: Group A1
Participants were scheduled to receive one dose of Chimpanzee adenovirus HBV vaccine (ChAd155-hIi-HBV) low dose formulation on Day 1, one dose of Modified Vaccinia Ankara HBV vaccine (MVA-HBV) low dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 low dose formulation, one on Day 113 and one on Day 169.
干预措施: ChAd155-hIi-HBV low dose formulation (Biological)
Step A: Group A1
Participants were scheduled to receive one dose of Chimpanzee adenovirus HBV vaccine (ChAd155-hIi-HBV) low dose formulation on Day 1, one dose of Modified Vaccinia Ankara HBV vaccine (MVA-HBV) low dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 low dose formulation, one on Day 113 and one on Day 169.
干预措施: HBc-HBs/AS01B-4 low dose formulation (Biological)
Step A: Group A1
Participants were scheduled to receive one dose of Chimpanzee adenovirus HBV vaccine (ChAd155-hIi-HBV) low dose formulation on Day 1, one dose of Modified Vaccinia Ankara HBV vaccine (MVA-HBV) low dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 low dose formulation, one on Day 113 and one on Day 169.
干预措施: MVA-HBV low dose formulation (Biological)
Step A: Group A2
Participants were scheduled to receive four doses of HBc-HBs/AS01B-4 low dose formulation, one dose each on Day 1, Day 57, Day 113 and Day 169.
干预措施: HBc-HBs/AS01B-4 low dose formulation (Biological)
Step A: Group A3
Participants were scheduled to receive four doses of placebo, one dose each on Day 1, Day 57, Day 113 and Day 169.
干预措施: Placebo (Drug)
Step B: Group B1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation on Day 1, one dose of MVA-HBV high dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 high dose formulation, one on Day 113 and one on Day 169.
干预措施: ChAd155-hIi-HBV high dose formulation (Biological)
Step B: Group B1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation on Day 1, one dose of MVA-HBV high dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 high dose formulation, one on Day 113 and one on Day 169.
干预措施: HBc-HBs/AS01B-4 high dose formulation (Biological)
Step B: Group B1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation on Day 1, one dose of MVA-HBV high dose formulation on Day 57, and two doses of HBc-HBs/AS01B-4 high dose formulation, one on Day 113 and one on Day 169.
干预措施: MVA-HBV high dose formulation (Biological)
Step B: Group B2
Participants were scheduled to receive four doses of HBc-HBs/AS01B-4 high dose formulation, one dose each on Day 1, Day 57, Day 113 and Day 169.
干预措施: HBc-HBs/AS01B-4 high dose formulation (Biological)
Step B: Group B3
Participants were scheduled to receive two doses of placebo, one on Day 1 and one on Day 57, one dose of ChAd155-hIi-HBV high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation on Day 169.
干预措施: ChAd155-hIi-HBV high dose formulation (Biological)
Step B: Group B3
Participants were scheduled to receive two doses of placebo, one on Day 1 and one on Day 57, one dose of ChAd155-hIi-HBV high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation on Day 169.
干预措施: MVA-HBV high dose formulation (Biological)
Step B: Group B3
Participants were scheduled to receive two doses of placebo, one on Day 1 and one on Day 57, one dose of ChAd155-hIi-HBV high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation on Day 169.
干预措施: Placebo (Drug)
Step C: Group C1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation co-administered with one dose of HBc-HBs/AS01B-4 high dose formulation on Day 1, and 3 doses of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 57, Day 113 and Day 169.
干预措施: MVA-HBV high dose formulation (Biological)
Step C: Group C1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation co-administered with one dose of HBc-HBs/AS01B-4 high dose formulation on Day 1, and 3 doses of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 57, Day 113 and Day 169.
干预措施: ChAd155-hIi-HBV high dose formulation (Biological)
Step C: Group C1
Participants were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation co-administered with one dose of HBc-HBs/AS01B-4 high dose formulation on Day 1, and 3 doses of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 57, Day 113 and Day 169.
干预措施: HBc-HBs/AS01B-4 high dose formulation (Biological)
Step C: Group C2
Participants were scheduled to receive two co-administered doses of placebo on Day 1, two co-administered doses of placebo on Day 57, one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 169.
干预措施: ChAd155-hIi-HBV high dose formulation (Biological)
Step C: Group C2
Participants were scheduled to receive two co-administered doses of placebo on Day 1, two co-administered doses of placebo on Day 57, one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 169.
干预措施: HBc-HBs/AS01B-4 high dose formulation (Biological)
Step C: Group C2
Participants were scheduled to receive two co-administered doses of placebo on Day 1, two co-administered doses of placebo on Day 57, one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 169.
干预措施: MVA-HBV high dose formulation (Biological)
Step C: Group C2
Participants were scheduled to receive two co-administered doses of placebo on Day 1, two co-administered doses of placebo on Day 57, one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 113 and one dose of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation on Day 169.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 1
时间窗: Within 7 days after vaccination 1 occurring on Day 1
Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = ChAd155-hIi-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = Placebo / Vaccine B = Placebo.
Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 2
时间窗: Within 7 days after vaccination 2 occurring on Day 57
Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = Placebo / Vaccine B = Placebo.
Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 3
时间窗: Within 7 days after vaccination 3 occurring on Day 113
Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For step C: Group C2, Vaccine A = ChAd155-hIi-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation.
Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 4
时间窗: Within 7 days after vaccination 4 occurring on Day 169
Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation.
Number of Participants Reporting Any Solicited Systemic Events After Vaccination 1
时间窗: Within 7 days after vaccination 1 occurring on Day 1
Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature greater than or equal to (\>=) 38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Solicited Systemic Events After Vaccination 2
时间窗: Within 7 days after vaccination 2 occurring on Day 57
Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Solicited Systemic Events After Vaccination 3
时间窗: Within 7 days after vaccination 3 occurring on Day 113
Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/ 100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Solicited Systemic Events After Vaccination 4
时间窗: Within 7 days after vaccination 4 occurring on Day 169
Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Unsolicited Adverse Events (AEs) After Vaccination 1
时间窗: Within 30 days after vaccination 1 occurring on Day 1
An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Unsolicited AEs After Vaccination 2
时间窗: Within 30 days after vaccination 2 occurring on Day 57
An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Unsolicited AEs After Vaccination 3
时间窗: Within 30 days after vaccination 3 occurring on Day 113
An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants Reporting Any Unsolicited AEs After Vaccination 4
时间窗: Within 30 days after vaccination 4 occurring on Day 169
An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 1
时间窗: Within 30 days after vaccination 1 occurring on Day 1
The assessed parameters were: * hematological: haemoglobin decrease, white blood cells (WBCs) increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin international normalized ratio (INR) increase; * biochemical: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma glutamyl transferase (GGT), creatinine; * urinalysis: protein, glucose, red blood cells (RBCs). The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.
Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 2
时间窗: Within 30 days after vaccination 2 occurring on Day 57
The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Not done = parameter value missing for the specified parameter.
Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 3
时间窗: Within 30 days after vaccination 3 occurring on Day 113
The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.
Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 4
时间窗: Within 30 days after vaccination 4 occurring on Day 169
The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.
Number of Participants Reporting Serious Adverse Events (SAEs)
时间窗: From Day 1 until Day 337
An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or in other situations that were considered serious per medical or scientific judgment.
Number of Participants Reporting Potential Immune-mediated Diseases (pIMDs)
时间窗: From Day 1 until Day 337
pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Number of Participants Reporting Liver Disease-related (LDR) Adverse Events of Special Interest (AESIs)
时间窗: From Day 1 until Day 337
LDR AESIs are defined as adverse events related to the underlying chronic HBV infection and characterized by one or more of the following: * ALT flares: Elevation of ALT \> 3 X Upper Limit of Normal (ULN): Mild: \> 3-5 X ULN, Moderate: \> 5-10 X ULN, Severe: \> 10 X ULN. * ALT flares with other substantial biochemical changes: Bilirubin \>= 2 X ULN, And/or INR \>1.5. * Hepatic decompensation: occurrence of one or more of the following events: ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy. * HBV-Deoxyribonucleic Acid (DNA) breakthrough: any increase in serum HBV DNA by \>1 log10 from nadir or redetection of serum HBV DNA at levels 10-fold the Lower Limit of Quantification (LLOQ) of the viral load after HBV DNA was undetectable.
Number of Participants Reporting Hematological AESIs
时间窗: From Day 1 until Day 337
Hematological AESIs are defined as: * spontaneous local or general bleeding with thrombocytes \<50,000 platelets/cubic millimeter (mm\^3), * anemia with hemoglobin (Hgb) \<9.5 gram/deciliter (g/dL).
Number of Participants Reporting Medically-attended Adverse Events (MAEs)
时间窗: From Day 1 until Day 337
MAEs are defined as events for which the participant received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.
次要结局
- Number of Seropositive Participants for Anti-hepatitis B Core Antibody (Anti-HBc)(At Days 1, 15, 71, 113, 127, 183, 337, 505 and 841)
- Anti-HBc Antibody Concentrations(At Days 1, 15, 71, 113, 127, 183, 337, 505 and 841)
- Number of Participants With Anti-hepatitis B Surface Antigen (Anti-HBs) Seroconversion(At Days 1,15, 71, 113, 127, 183, 337, 505 and 841)
- Anti-HBs Antibody Concentrations(At Days 1, 15, 71, 113, 127, 183, 337, 505 and 841)
- Number of Participants With Anti-HBs Antibody Concentration >=10 mIU/mL(At Days 1,15, 71, 113, 127, 183, 337, 505 and 841)
- Number of Participants With Anti-HBs Antibody Concentration >=100 mIU/mL(At Days 1, 15, 71, 113, 127, 183, 337, 505 and 841)
- Frequency of HBs-specific CD4+ T-cells(At Days 1, 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841)
- Frequency of HBs-specific CD8+ T-cells(At Days 1, 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841)
- Frequency of HBc-specific CD4+ T-cells(At Days 1, 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841)
- Frequency of HBc-specific CD8+ T-cells(At Days 1, 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841)
- Number of Responders for HBs-specific CD4+ T-cells at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841 compared to pre-vaccination (Day 1))
- Number of Responders for HBs-specific CD8+ T-cells at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841 compared to pre-vaccination (Day 1))
- Number of Responders for HBc-specific CD4+ T-cells at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841 compared to pre-vaccination (Day 1))
- Number of Responders for HBc-specific CD8+ T-cells at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841 compared to pre-vaccination (Day 1))
- Number of Participants With ≥ 0.5 Log Decrease of qHBsAg at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 31, 57, 87, 113, 143, 169, 199, 225, 281, 337, 421, 505, 673, 841 compared to pre-vaccination (Day 1))
- Number of Participants With ≥ 1 Log Decrease of qHBsAg at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 31, 57, 87, 113, 143, 169, 199, 225, 281, 337, 421, 505, 673, 841 compared to pre-vaccination (Day 1))
- Number of Participants With qHBsAg Loss at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 31, 57, 87, 113, 143, 169, 199, 225, 281, 337, 421, 505, 673, 841 compared to pre-vaccination (Day 1))
- Number of Participants With Any Log-changes in qHBsAg at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 31, 57, 87, 113, 143, 169, 199, 225, 281, 337, 421, 505, 673, 841 compared to pre-vaccination (Day 1))
- Number of Participants With qHBsAg Loss and Anti-HBs Seroconversion at the Specified Time Points Compared to Pre-vaccination (Day 1)(At Days 113, 337, 505 and 841 compared to pre-vaccination (Day 1))
- Evaluation of qHBsAg Geometric Mean Concentrations(At Days 1, 31, 57, 87, 113, 143, 169, 199, 225, 281, 337, 421, 505, 673, 841)
- Number of Participants Reporting Any SAEs and SAEs Causally Related to an Investigational Vaccine(From Day 1 until Day 841)
- Number of Participants Reporting MAEs(From Day 1 until Day 841)
- Number of Participants Reporting pIMDs(From Day 1 until Day 841)
- Number of Participants Reporting LDR AESIs(From Day 1 until Day 841)
- Number of Participants Reporting Spontaneous Local or General Bleeding With Thrombocytopenia(From Day 1 until Day 841)
- Number of Participants Reporting Anemia(From Day 1 until Day 841)
- Number of Participants Reporting AEs/SAEs Leading to Study Withdrawal(From Day 1 until Day 841)
- Number of Participants Reporting Pregnancies(From Day 1 until Day 841)
- Number of Participants With Outcomes of Reported Pregnancies(From Day 1 until Day 841)