NCT06566248招募中2 期
Randomized, Double-blind, Placebo-controlled Phase IIa Trial to Evaluate the Efficacy and Safety of Combined/Uncombined Nucleoside (Acid) Analogues of TQA3810 Tablets in Primary/Treated Patients With Chronic Hepatitis B
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during the study period
研究概览
简要总结
To evaluate the efficacy and safety of combined/uncombined nucleoside (acid) analogues of TQA3810 tablets.
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
- Single (Participant)
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
- •Age 18-70 (including boundary values), male or female.
- •Serum virological criteria: serum HBsAg positive for more than 6 months or evidence of chronic hepatitis B for more than 6 months. During the screening period, 100 IU/ml≤HBsAg quantification ≤10000 IU/ml.
- •No obvious cirrhosis was found by the researchers.
- •The subjects can communicate well with the researchers, understand and comply with the requirements of this study, and understand and sign the informed consent.
- •The 12-lead electrocardiogram was normal, or there were no clinically significant abnormal values as assessed by the investigator.
- •Treated patients must meet the following conditions:
- •Subjects must have received oral nucleoside (acid) therapy (entecavir/ Tenofovir alafenamide Fumarate tablets/Tenofovir Disoproxil Fumarate Tablets) for ≥6 months prior to screening and stable treatment regimen for ≥3 months prior to screening.
- •Patients with medical history 6 months or more before enrollment had HBV DNA< the lower limit of normal detection, and hepatitis B virus (HBV) DNA<20 IU/mL was detected by Roche COBAS Taqman during the screening period.
- •Newly treated patients need to meet the following conditions:
- •At the time of screening, subjects had never received antiviral treatment for chronic hepatitis B (oral nucleoside drugs and interferon), or had received irregular antiviral treatment in the past, and had not received any antiviral treatment for chronic hepatitis B in the first 3 months of enrollment.
- •HBV DNA≥2000 IU/mL(Roche COBAS Taqman).
排除标准
- •Combined with other viral infections such as hepatitis A virus，hepatitis C virus, hepatitis D virus, hepatitis E virus, human immunodeficiency virus，syphilis (syphilis antibody positive by the researchers to determine the need for treatment). If hepatitis C virus (HCV) antibody positive, HCV RNA negative can not be excluded.
- •Patients with significant fibrosis or cirrhosis before or at the time of screening: liver histopathological findings indicating Metavir F3 or F4 within 1 year before screening; FibroScan≥ 9.7 kPa 6 months before screening in treated patients and ≥ 12.4 kPa 6 months before screening in newly treated patients; Abdominal ultrasonography suggested suspected cirrhosis. Previous history of hepatic decompensation or screening period of hepatic decompensation, such as ascites, hepatic encephalopathy, esophageal and gastric varices bleeding, etc.
- •Patients with a history of hepatocellular carcinoma (HCC) before or at the time of screening, or who may be at risk for HCC, such as suspicious nodules on imaging, or abnormal AFP (AFP>50ng/mL), should be excluded from HCC before enlisting.
- •A history of malignant tumors within 5 years prior to screening, except for certain cancers that can be completely cured by surgical resection (such as skin basal cell carcinoma). Subjects being evaluated for active or suspected malignancy at the time of screening.
- •Patients with other chronic liver diseases, including but not limited to autoimmune liver disease, alcoholic liver disease, hepatolenticular degeneration, etc.
- •Have previously received organ transplantation and bone marrow transplantation.
- •Patients with uncontrolled thyroid disease.
- •Eye diseases: including fundus lesions (cotton wool changes in the fundus with symptoms) and retinopathy.
- •Autoimmune diseases include but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis, autoimmune uveitis, etc.
- •Current alcohol and drug abuse was determined by the investigator. Subjects with a history of excessive alcohol use. A history of excessive alcohol use was defined as alcohol consumption >210g per week for men and >140g for women in the past 12 months. Alcohol intake (g) = amount of alcohol consumed (ml) × alcohol degree % × 0.
- •Blood transfusion ≤2 months before screening and/or blood donation ≤1 month before screening. Note: Subjects were not allowed to donate blood throughout the study period.
- •Have a history of allergy to the experimental drug or its excipients;
- •Female subjects are pregnant, breastfeeding or have positive pregnancy results during the screening period or during the test;
- •Those that researchers believe should not be included.
研究组 & 干预措施
Part A: TQA3810 tablets+NUC
Experimental
Part A: TQA3810 tablets+NUC：A total of 4 dose groups were set up, which were respectively TQA3810 tablets 0.1mg once a day, 0.2mg once every two days, 0.3mg twice a week and 0.2mg once a day combined with oral nucleoside (acid) drugs (NUC) group for 24 weeks.
干预措施: TQA3810 tablets+NUC (Drug)
Part A: Placebo+NUC
Placebo Comparator
Part A: Placebo+NUC: Placebo combined with oral nucleoside (acid) drugs (NUC) group was treated for 24 weeks.
干预措施: Placebo+NUC (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during the study period
时间窗: Up to 52 months
The study required collection of any adverse medical events, whether causally associated with the investigational drug or not, from the time the subject signed the informed consent to 28 days after the end of study medication or the initiation of other anti-HBV therapy (whichever came first).
次要结局
- Changes in serum HBsAg(24 weeks)
- HBeAg level change(24 weeks)
- Peak Concentration(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Apparent volume of distribution (Vd/F)(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Steady state minimal concentration(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- HBV DNA level changes and drug resistance monitoring(24 weeks)
- HBsAg clearance and/or serological conversion(24 weeks)
- HBeAg clearance and/or serological conversion(24 weeks)
- HBsAg level decreased by ≥0.5log10 IU/ml(24 weeks)
- Changes of HBV RNA and hepatitis B core-related antigen (HBcrAg) levels during treatment(24 weeks)
- Peak time (Tmax)(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Area under blood concentration-time curve (AUC)(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Plasma clearance(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Elimination half-life time(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Peaking Time(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Steady state maximum concentration(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Area under steady-state blood concentration-time curve(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Pharmacodynamic characteristics (IFN-γ, IL-1RA, CCL2, CCL4, CCL8, CCL11, CCL20, CXCL8, IL-12p70, IL-12p40, TNF-α, CRP)(In 60 minutes pre-dose on day 1, 0.5, 1, 2, 4, 12 hours after dose; Day 15 within 60 minutes pre-dose; Day 29 within 60 minutes pre-dose; Day 57 within 60 minutes pre-dose; Day 85 within 60 minutes pre-dose, 0.5, 1, 2, 4, 12 hours after dose)
- Evaluate whether TQA3810 will affect the heart rate-corrected QT interval (QTc) of newly treated/treated chronic hepatitis B patients(24 weeks)
研究者
研究点 (6)
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