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临床试验/NCT03258710
NCT03258710已完成4 期

A Multi-centre, One-arm Prospective Study to Evaluate Efficacy and Safety of Switching From Entecavir (ETV) to Tenofovir Disoproxil Fumarate (TDF) in Japanese Chronic Hepatitis B HBeAg-positive and HBV-DNA Undetectable Subjects

GlaxoSmithKline1 个研究点 分布在 1 个国家目标入组 75 人开始时间: 2017年10月2日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
75
试验地点
1
主要终点
Percentage of Participants Who Achieved 0.25 Logarithm to the Base 10 (Log10) Hepatitis B Surface Antigen (HBsAg) Reduction From the Baseline at Week 48
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Tenofovir Disoproxil Fumarate is a nucleos(t)ide analogue that inhibits Hepatitis B Virus (HBV) growth, and is marketed in Japan with an indication for inhibition of HBV growth in subjects with chronic hepatitis B associated with HBV growth and abnormal liver function. This study has been planned to evaluate the virological effects and safety of switching from ETV to TDF in chronic hepatitis B (hepatitis B e-antigen [HBeAg])-positive and HBV- deoxyribonucleic acid (DNA) undetectable subjects. This study is designed as a multi-center, one-arm, post-marketing clinical study to investigate the HBsAg reduction in subjects who have not achieved the long-term goal, the loss of hepatitis B surface antigen (HBsAg). The study will be conducted in HBeAg-positive and HBV-DNA undetectable subjects treated with ETV. After switching ETV to TDF, TDF will be administered for 96 weeks. Approximately 80 subjects will be screened to achieve 65 evaluable subjects.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
20 Years 至 69 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Subjects must be 20 to 69 years of age inclusive, at the time of signing the informed consent
  • •Male and female subjects. A female subject is eligible to participate if she is not pregnant and not breastfeeding, and at least one of the following conditions applies:
  • •Not a woman of childbearing potential (WOCBP), OR
  • •A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 days after the last dose of study treatment
  • •Capable of giving signed informed consent form (ICF)
  • •Subjects with chronic hepatitis B (CHB) (excluding hospitalized subjects)
  • •Subjects treated with ETV for at least 2 years prior to initiation of study treatment.
  • •The serum HBV-DNA level at screening is below the limit of quantitation (< 2.1 Log10 copies/milliliter [mL] or < 20 international unit [IU]/mL).
  • •Subjects with serum HBeAg positive at screening
  • •Meet either of the following serum HBsAg levels at screening:
  • •Serum HBsAg 80 < to < 800 IU/mL and fluctuation range is equal or more than -0.1 Log10 IU/mL per year
  • •Serum HBsAg >=800 IU/mL
  • •Meet all of the following criteria at screening:
  • •Creatinine clearance (CLcr) >=70 mL/minute. CLcr is calculated using the following Cockcroft-Gault formula.
  • •Male: CLcr = (body weight in kilogram [kg] multiplied by [140 minus age in years]) divided by (72 multiplied by serum creatinine [milligram {mg}/deciliter {dL}]) Female: CLcr = CLcr (male) multiplied by 0.85
  • •Hemoglobin >= 8 gram/dL
  • •WBC >=1000 per cubic millimeter (mm^3)

排除标准

  • •QTc > 450 millisecond (msec) or > 480 msec for subjects with bundle branch block
  • •Received any interferon or Hepatitis B vaccine therapy within 24 weeks prior to initiation of the study treatment.
  • •Received overdose of nonsteroidal anti-inflammatory drugs (NSAIDs) (excluding temporary or topical use) within 7 days prior to initiation of the study treatment.
  • •Received any of the following drugs within 8 weeks prior to initiation of the study treatment (excluding topical products such as ointment and/or cream etc).
  • •Drugs causing renal impairment (examples: aminoglycosides, amphotericin B, vancomycin, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine, some contrast mediums [ionic high-osmolar contrast media, ionic low-osmolar contrast media]
  • •Competitors of renal excretion (except temporary use, example: probenecid)
  • •Immunosuppressants (examples: azathioprine, cycolphosphamide) or chemotherapeutics (example: etoposide)
  • •Glucocorticoid preparation
  • •Received TDF, Adefovir pivoxil (ADV) or Tenofovir Alafenamide Fumarate (TAF) within 2 years prior to initiation of the study treatment
  • •Participation in another clinical study within 6 months prior to screening, or planned participation in another clinical study simultaneously with this study.
  • •Co-infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
  • •Subjects with serious complication other than compensated CHB (cancer, significant renal, cardiovascular, pulmonary, or neurological disease, uncontrollable diabetes, etc.)
  • •Received or have a plan for solid organ or bone marrow transplantation
  • •Has proximal tubulopathy.
  • •Subjects with decompensated CHB who meet the following: direct bilirubin > 1.5 times upper limit of normal (ULN), Prothrombin Time (PT) < 60%, platelets < 75,000/mm3 and serum albumin < 3.0 g/dL
  • •Autoimmune hepatitis (Antinuclear titer > 1:160), excluding CHB
  • •Subjects with or suspected of having hepatocellular carcinoma (HCC) (including both primary and metastatic) from diagnostic imaging at screening, or with serum alpha-fetoprotein (AFP) > 50 nanogram (ng)/mL at screening
  • •History of HCC (except subjects who underwent resection or received curative treatment by radiofrequency, and with AFP <=10 ng/mL at screening)
  • •Woman who is pregnant, possibly pregnant, lactating or planning a pregnancy during the study period.
  • •Psychiatry disorder or cognitive disorder that may affect the subject's ability to give informed consent or to follow specified study procedures.
  • •Subjects with a history of alcohol or drug abuse
  • •Subjects whom the investigator (or sub-investigator) considers ineligible for the study.
  • •Subjects with hypersensitivity to study treatments or their components, nucleoside and/or nucleotide analogues. Subjects with drug allergy that, in the investigator's (sub-investigator's) [or medical monitor's] opinion, labeled contraindication for participation in the study, or other allergy.

研究组 & 干预措施

All subjects treated with Tenofovir Disoproxil Fumarate

Experimental

Subjects with on-going ETV treatment will be switched to Tenofovir Disoproxil Fumarate treatment. Subjects will start TDF on the day ETV is discontinued, without having overlapping treatment periods. All subjects will receive one tablet of TDF 300 mg once daily orally for 96 weeks.

干预措施: Tenofovir Disoproxil Fumarate (Drug)

结局指标

主要结局

Percentage of Participants Who Achieved 0.25 Logarithm to the Base 10 (Log10) Hepatitis B Surface Antigen (HBsAg) Reduction From the Baseline at Week 48

时间窗: Baseline (Day 1, Pre-dose) and at Week 48

Blood samples were collected to evaluate the HBsAg reduction from Baseline at Week 48. HBsAg reduction potential was obtained by evaluating log10 observation values minus log10 Baseline values. The HBsAg responder values were\<=-0.25 log10 and non-responder values were \>-0.25 log10 . Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Full analysis set (FAS) Population is defined as population of all participants enrolled in the study, excluding those who meet either of the following criteria: who have not received any dose of study treatment and who have no efficacy data (HBsAg, HBV-DNA, hepatitis B core-related antigen \[HBcrAg\], HBeAg, hepatitis B surface antibody \[HBsAb\],Hepatitis B envelope antibody \[HBeAb\], alanine aminotransferase \[ALT\]) from at least 15 days after the start of study treatment. Data for HBsAg responders have been presented.

次要结局

  • Change From Baseline Log Values for HBcrAg Titer at Weeks 24, 48 and 96(Baseline (Day 1, Pre-dose) and at Weeks 24, 48 and 96)
  • Absolute Values for Clinical Chemistry Parameter: Alpha-fetoprotein (AFP)(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatinine Kinase (CPK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH)(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Clinical Chemistry Parameters: Amylase and Lipase(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Percentage of Participants Who Achieved HBsAg/Ab Seroconversion at Weeks 24, 48 and 96(At Weeks 24, 48 and 96)
  • Absolute Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Percentage of Participants Who Achieved HBeAg/Ab Seroconversion at Weeks 24, 48 and 96(At Weeks 24, 48 and 96)
  • Number of Participants Who Reported Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)(Up to Week 96)
  • Change From Baseline Log Values for HBsAg Titer at Weeks 24, 48 and 96(Baseline (Day 1, Pre-dose) and at Weeks 24, 48 and 96)
  • Absolute Values for Clinical Chemistry Parameters: Albumin and Total Protein(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Percentage of Participants Who Achieved 0.25 Log10 HBsAg Reduction From the Baseline at Weeks 24 and 96(Baseline (Day 1, Pre-dose) and at Weeks 24 and 96)
  • Percentage of Participants Who Achieved HBsAg Loss at Weeks 24, 48 and 96(At Weeks 24, 48 and 96)
  • Percentage of Participants Who Achieved HBeAg Loss at Weeks 24, 48 and 96(At Weeks 24, 48 and 96)
  • Percentage of Lymphocytes at Indicated Time Points(At Weeks 36, 48, 60, 72, 84 and 96)
  • Percentage of Monocytes at Indicated Time Points(At Weeks 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Hematology Parameter: Hemoglobin(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Lactic Acid, Sodium, Phosphorus and Blood Urea Nitrogen (BUN)(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Clinical Chemistry Parameter: Creatinine Clearance(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Number of Participants With Abnormal Urinalysis Values at Weeks 4, 12, 24, 36 and 48(Weeks 4, 12, 24, 36 and 48)
  • Absolute Values for Clinical Chemistry Parameter: Glomerular Filtration Rate (GFR)(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Percentage of Basophils at Indicated Time Points(At Weeks 36, 48, 60, 72, 84 and 96)
  • Percentage of Total Neutrophils at Indicated Time Points(At Weeks 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Hematology Parameter: Hematocrit(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Hematology Parameter: Prothrombin Time(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Percentage of Eosinophils at Indicated Time Points(At Weeks 36 , 48, 60, 72, 84 and 96)
  • Absolute Values for Hematology Parameters: Platelet Count and White Blood Cell (WBC) Count(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Hematology Parameter: Red Blood Cell (RBC) Count(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Change From Baseline Values for Beta-2-microglobulin(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Change From Baseline Values for Urine Creatinine Concentration and Urine Phosphate(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Heart Rate(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Absolute Values for Temperature(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Change From Baseline Values for Bone Density(Baseline (Day -1) and at Weeks 24, 48, 72 and 96)
  • Number of Participants With Abnormal Urinalysis Values at Weeks 60, 72, 84 and 96(Weeks 60, 72, 84 and 96)
  • Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1, Pre-dose) and at Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96)
  • Number of Participants With Worst Case Post-Baseline Electrocardiogram (ECG) Values(Up to Week 96)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (1)

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