Randomized, Double-blind, Placebo-controlled Phase Ib/IIa Clinical Trial to Evaluate the Efficacy and Safety of TQA3605 Tablets Monotherapy or in Combination With Nucleoside (Acid) Analogues in Treatment-naïve Patients and Treated Patients With Chronic Hepatitis B
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 88
- 试验地点
- 3
- 主要终点
- The incidence of adverse events (AEs)
研究概览
简要总结
This is a randomized, double-blind Phase Ib/IIa multicenter trial. All eligible subjects will receive TQA3605 tablets or placebo in combination with nucleoside (acid) analogues. A total of 64 subjects will be enrolled.
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
- •Subjects voluntarily participate in this study and sign informed consent;
- •Male and female, ≥18 years old and ≤70 years old (subject to the date of signing the informed consent);
- •Patients diagnosed with chronic hepatitis B (CHB) who have been serum HBsAg positive for more than 6 months and HBeAg positive or negative ;
- •The liver fibrosis ultrasound transient imaging elastic technology (Fibroscan/FibroTouch) showed that the liver hardness (LSM) was less than 12.4 Kpa;
- •Patients with chronic hepatitis B after treatment;
- •Treatment-naïve patients of chronic hepatitis B patients;
排除标准
- •Complicated with other infected disease such as hepatitis A virus (HAV), hepatitis C virus (HCV), Hepatitis D virus (HDV), hepatitis E virus (HEV), human immunodeficiency virus (HIV), syphilis (syphilis antibody positive and need treatment determined by the investigator);
- •Abdominal ultrasound or other imaging or histology showed suspected cirrhosis or other liver disease before or during screening;
- •Patients have a history of hepatocellular carcinoma (HCC) before or at the time of screening, or may be at risk for HCC;
- •Active autoimmune disease diagnosed with immunodeficiency or undergoing systemic therapy which was continuing within 2 weeks before first dosing;
- •Currently being treated with nephrotoxic drugs or drugs that alter renal excretion;
- •Abnormal thyroid function;
- •Renal diseases such as chronic kidney disease and renal insufficiency or creatinine clearance (CLCr) <60 ml/min during the screening period;
- •Hematologic and biochemical abnormalities;
- •History of allergy to the investigational drug or its excipients;
- •Recipients of solid organs or bone marrow transplants;
- •A history of malignant tumors within the past 5 years;
- •Interstitial lung disease, acute lung disease, etc.;
- •Uncontrolled systemic diseases such as high blood pressure and diabetes;
- •Have used any investigational drug or participated in a clinical trial within one month prior to the administration of study drug;
- •Those who received live attenuated vaccine within 28 days before the start of study treatment, inactivated vaccine within 7 days, or planned vaccination during the study period;
- •The investigator determines that there is any medical or psychiatric condition that puts the subject at risk, interferes with participation in the study, or interferes with the interpretation of the study results;
- •Female subjects that were pregnant, lactating or had a positive pregnancy result during the screening period or during the trial; Male and female patients with reproductive potential who were unwilling to use effective contraceptive methods during the study period;
- •Subjects who have any medical condition that may affect the absorption of oral drugs;
- •Within 12 weeks prior to screening, treated chronic hepatitis B patients who had stopped taking nucleoside (acid) analogues for more than 14 consecutive days;
- •Those considered unsuitable for enrollment by the investigators.
研究组 & 干预措施
Placebo +Nucleoside (acid) analogs (NAs) combination therapy 24 weeks
Placebo and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
50 mg of TQA3605 tablets +NAs combination therapy 24 weeks
50 mg of TQA3605 tablets and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: TQA3605 tablets (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy 24 weeks
Placebo and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Placebo (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy 24 weeks
Placebo and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Entecavir dispersible tablets (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy 24 weeks
Placebo and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
50 mg of TQA3605 tablets +NAs combination therapy 24 weeks
50 mg of TQA3605 tablets and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Entecavir dispersible tablets (Drug)
50 mg of TQA3605 tablets +NAs combination therapy 24 weeks
50 mg of TQA3605 tablets and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
50 mg of TQA3605 tablets +NAs combination therapy 24 weeks
50 mg of TQA3605 tablets and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
100 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 100mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: TQA3605 tablets (Drug)
100 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 100mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Entecavir dispersible tablets (Drug)
100 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 100mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
100 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 100mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
200 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 200mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: TQA3605 tablets (Drug)
200 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 200mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Entecavir dispersible tablets (Drug)
200 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 200mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
200 mg of TQA3605 tablets +NAs combination therapy 48 weeks
TQA3605 is taken orally 200mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy
Placebo taken orally once daily, continue for 12 weeks. Placebo was then combined with nucleoside (acid) analogues (once daily) for 36 weeks
干预措施: Placebo (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy
Placebo taken orally once daily, continue for 12 weeks. Placebo was then combined with nucleoside (acid) analogues (once daily) for 36 weeks
干预措施: Entecavir dispersible tablets (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy
Placebo taken orally once daily, continue for 12 weeks. Placebo was then combined with nucleoside (acid) analogues (once daily) for 36 weeks
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
Placebo +Nucleoside (acid) analogs (NAs) combination therapy
Placebo taken orally once daily, continue for 12 weeks. Placebo was then combined with nucleoside (acid) analogues (once daily) for 36 weeks
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
100 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 100mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: TQA3605 tablets (Drug)
100 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 100mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Entecavir dispersible tablets (Drug)
100 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 100mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
100 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 100mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
200 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 200mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: TQA3605 tablets (Drug)
200 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 200mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Entecavir dispersible tablets (Drug)
200 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 200mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
200 mg of TQA3605 tablets +NAs combination therapy
TQA3605 was taken orally 200mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
300 mg of TQA3605 tablets+NAs combination therapy
TQA3605 was taken orally 300mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: TQA3605 tablets (Drug)
300 mg of TQA3605 tablets+NAs combination therapy
TQA3605 was taken orally 300mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Entecavir dispersible tablets (Drug)
300 mg of TQA3605 tablets+NAs combination therapy
TQA3605 was taken orally 300mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir disoproxil fumarate tablet (Drug)
300 mg of TQA3605 tablets+NAs combination therapy
TQA3605 was taken orally 300mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.
干预措施: Tenofovir alafenamide fumarate tablet (Drug)
结局指标
主要结局
The incidence of adverse events (AEs)
时间窗: Up to 48 weeks
The incidence of adverse events (AEs) during treatment
Severity of adverse events (AEs)
时间窗: Up to 48 weeks
The severity of adverse events (AEs) during treatment
Incidence of serious adverse events (SAEs)
时间窗: Up to 48 weeks
The incidence of serious adverse events (SAEs) during treatment
Severity of serious adverse events (SAEs)
时间窗: Up to 48 weeks
The severity of serious adverse events (SAEs) during treatment
次要结局
- Incidence of abnormal laboratory test values(Up to 48 weeks)
- Severity of abnormal laboratory test values(Up to 48 weeks)
- Deoxyribonucleic acid level of hepatitis B virus(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Hepatitis B surface antigen(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Hepatitis B e antigen(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Serologic clearance and/or serologic conversion of HBsAg(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Serologic clearance and/or serologic conversion of HBeAg(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Virological breakthrough rate(At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study)
- Peak time (Tmax)(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Peak concentration(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Area under blood concentration-time curve (AUC)(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Apparent volume of distribution (Vd/F)(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Plasma clearance(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Elimination half-life(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Steady state peak time(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Steady state maximum concentration(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)
- Steady state minimal concentration(pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.)