To Evaluate the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets in Multiple-center, Randomized, Double-blind, Placebo-controlled Multiple-dose, Multiple-administration Study in Patients With Chronic Hepatitis B
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of patients with chronic HBV infection with treatment-related adverse events and laboratory abnormalities.
研究概览
简要总结
To Evaluate the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets in Multiple-center, Randomized, Double-blind, Placebo-controlled Multiple-dose, Multiple-administration Study in Patients With Chronic Hepatitis B (CHB)
详细描述
This study includes 3 cohorts of 25 mg BID, 50 mg BID and 100 mg BID. 30 patients with chronic hepatitis B will be enrolled in this study and each cohort will enroll 10 patients (GST-HG141 tablets : PBO=8:2). All enrolled patients will be given research drugs twice a day for 28 days (D28 was administered only once in the morning). And each cohort requires at least 4 subjects with elevated ALT. Tolerability, pharmacodynamics and pharmacokinetics will be evaluated according to the protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign the informed consent before the study and fully understand the content and process of the study as well as the possible adverse drug reactions;
- •Be able to complete the study in accordance with protocol requirements;
- •Subjects (including partners) are willing to take effective contraceptive measures from completion of screening to 6 months after the last Administration;
- •Ages ranged from 18 to 70 years old (including 18 and 70 years old);
- •Male subjects weighing no less than 45 kg, and female subjects weighing no less than 40 kg. [Body mass index (BMI) = body weight (kg) / height 2 (m^2)], body mass index is in the range of 18 ~ 32 kg / m^2 (including critical value);
- •Patients with HBsAg-positive for at least 6 months (based on outpatient/inpatient medical records or laboratory report; or with IgM HBcAb-negative and HBsAg-positive when screening;
- •Patients without interferon/nucleoside analogue treatment when screening, or interferon treatment was stopped more than 1 year ago, and nucleoside analogue treatment was stopped more than 6 months ago.
- •For HBeAg-positive patients, HBV DNA ≥ 2×10^5 IU/mL; For HBeAg-negative patients, HBV DNA ≥ 2×10^4 IU/mL;
- •Patients with Serum ALT less than 5×ULN when screening.
排除标准
- •Patients with suspected allergy to any component of the study drug or allergic constitution (multiple drug and food allergy)；
- •Patients who had major trauma or Large surgical operation within 3 months before screening or are planning to take surgical treatment during the study ;
- •Patients who had blood donation or massive blood loss (≥400 mL), or had a blood transfusion within 3 months before screening; or had blood donation or massive blood loss (≥200 mL) within 1 months before screening;
- •Patients with smoking more than 5 cigarettes per day within 3 months before the study or heavy drinking within 4 weeks before screening (drinking more than 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine)；
- •Patients who had used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or had received live attenuated vaccine within 1 month before screening;
- •Patients who used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or who had received live attenuated vaccine within 1 month before screening;
- •Patients with clinically significant acute or chronic liver disease caused by non HBV infection (fatty liver disease is ruled out or recruited by researcher);
- •Patients with history of liver cirrhosis or progressive liver fibrosis (e.g., liver histopathology reported liver cirrhosis or endoscopy indicated esophageal and gastric varices);
- •Patients with confirmed or suspected decompensated hepatitis B cirrhosis including but not limited to: hepatic encephalopathy, hepatorenal syndrome, esophageal and gastric variceal bleeding, splenomegaly, ascites, primary liver cancer, etc. ;
- •Patients with history of other malignancies or complicating with other malignant tumors;
- •Patients complicating with severe circulatory, digestive, respiratory, urinary, blood, metabolism, immune, nervous and other systemic;
- •Patients with acute infection within 2 weeks before screening;
- •Patients who had participated in clinical trials of drugs or medical devices within 1 month before screening;
- •Patients who could not ban smoking, drinking, caffeinated food or drinks within 2 days before administration and during the study , and patients who have special dietary requirements and can not follow the unified diet;
- •Laboratory examination: platelet count<90×10^9/L; leukocyte count<3.0×10^9/L; neutrophil absolute value<1.3×10^9/L; serum total bilirubin>2×ULN; albumin<30 g/L; creatinine clearance rate≤60ml/min (calculated by MDRD formula); international standardization ratio value of prothrombin time (INR) >1.5;
- •Patients with Alpha fetoprotein (AFP) more than 50 UG / L or imaging findings of malignant liver lesions;
- •Patients with HCAb-positive , AIDS Ag/Ab-positive, or positive syphilis spirochemical Ab simultaneously RPR test-positive;
- •For patients with normal ALT or less than 2×ULN, LSM≥12.4 kPa; or for patients with ALT≥2×ULN, LSM≥17.0 kPa;
- •Patients with positive urine drug screening (morphine, marijuana) or alcohol breath test;
- •Patients with positive urine drug screening (morphine, marijuana) or alcohol breath test；
- •Patients with other factors that are not suitable to participate in this study in researcher's thought.
研究组 & 干预措施
GST-HG141
GST-HG141 tablets at varying dosages by mouth for 28 days
干预措施: GST-HG141 tablets (Drug)
Matching Placebo for GST-HG141
Placebos for GST-HG141 tablets at varying dosages by mouth for 28 days
干预措施: Matching Placebos for GST-HG141 tablets (Drug)
结局指标
主要结局
Number of patients with chronic HBV infection with treatment-related adverse events and laboratory abnormalities.
时间窗: Up to 33 days
Symptoms and physical examination, clinical laboratory examination, vital signs，12 lead ECG and adrenal ultrasounds were collected and assessed by CTCAE v5.0.
Cmax of GST-HG141
时间窗: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
Plasma samples were collected at different points for pharmacokinetic analysis
AUC of GST-HG141
时间窗: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
Plasma samples were collected at different points for pharmacokinetic analysis
t1/2 of GST-HG141
时间窗: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
Plasma samples were collected at different points for pharmacokinetic analysis
Cl/F of GST-HG141
时间窗: Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.
Plasma samples were collected at different points for pharmacokinetic analysis
次要结局
- The value of serum HBV DNA decreased from baseline(Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33)
- The value of serum HBV pgRNA decreased from baseline(Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33)
- The value of serum HBsAg decreased from baseline(Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33)
- The value of serum HBeAg decreased from baseline(Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33)