A Randomized, Double-Blind, Placebo-Controlled Phase III Trial With an Open-Label Extension to Evaluate the Efficacy and Safety of TQA3605 Tablets in Chronic Hepatitis B Virus-Infected Patients With Low-Level Viremia or Suboptimal Response After at Least 12 Months of NAs Therapy
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 930
- 试验地点
- 78
- 主要终点
- HBV DNA
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled Phase III study with an open-label extension. The purpose is to evaluate efficacy and safety in adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy, to demonstrate that TQA3605 Tablets combined with oral nucleos(t)ide analogues can improve efficacy with satisfactory safety profile compared with oral nucleos(t)ide analogues alone in this population. Approximately 930 adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy are planned to be enrolled in this study.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged 18-65 years (inclusive) at screening.
- •Able to communicate effectively with the investigator, understand and comply with all requirements of this study, and understand and sign the informed consent form.
- •Have received continuous treatment with nucleos(t)ide analogues (entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate or tenofovir amibufenamide) or NAs combination therapy for ≥ 12 months at screening, with a stable single regimen for ≥ 6 months (medication adherence > 90% in the past 12 months, with no treatment interruption exceeding 15 consecutive days).
- •Etiological evidence is available at screening to confirm chronic HBV infection of more than 1 year (HBsAg positive and/or HBV DNA positive for at least 1 year).
- •HBV DNA > 50 IU/mL detected by a local medical institution within 30 days prior to screening, which is reconfirmed as HBV DNA > 50 IU/mL by the central laboratory during the screening period.
- •HBeAg positive as confirmed by the central laboratory at screening.
- •Male trial participants with fertile female partners or female participants of childbearing potential are willing to use effective contraception from screening until 3 months after study discontinuation.
排除标准
- •Pregnant women (positive pregnancy test) or breastfeeding women.
- •Co-infection with other viruses such as HAV, HCV, HDV, HEV, HIV, or syphilis (participants with positive syphilis antibody who require treatment as judged by the investigator; Participants with positive HCV antibody and negative HCV RNA may not be excluded).
- •History of liver cirrhosis; or liver histopathology obtained within 1 year prior to screening indicating Metavir ≥ S3, Scheuer ≥ S3 or Ishak ≥ S4; or FibroScan result ≥ 9.0 kPa within 6 months prior to screening; or previous endoscopy revealing esophageal and gastric varices; or suspected liver cirrhosis identified on abdominal ultrasonography at screening, such as ascites, hepatic encephalopathy, and bleeding from esophageal and gastric varices.
- •History of hepatocellular carcinoma (HCC) or suspected HCC at or prior to screening (e.g., suspicious lesions on imaging, or AFP ≥ 50 ng/mL).
- •History of malignant tumor within 5 years prior to screening, except for certain malignancies that are completely curable after surgical resection (e.g., basal cell carcinoma of the skin). Trial participants under evaluation for active or suspected malignant tumor at screening.
- •Trial participants with other chronic liver diseases, including but not limited to autoimmune liver disease, alcoholic liver disease, Wilson's disease, metabolic dysfunction-associated steatohepatitis (MASH).
- •Clinically significant abnormal laboratory parameters at screening (abnormal values may be retested once): Hematology: white blood cell count less than 3 ×10⁹/L, neutrophil count less than 1.5 ×10⁹/L, platelet count less than 100 ×10⁹/L, or hemoglobin less than 100 g/L. Biochemistry: estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI formula ≤ 60 mL/min/1.73 m²; ALT or AST greater than 3 × ULN; total bilirubin greater than 2 × ULN; albumin less than 30 g/L; total cholesterol ≥ 7.75 mmol/L; triglycerides ≥ 3.42 mmol/L; serum uric acid greater than 420 μmol/L. Coagulation: international normalized ratio (INR) greater than 1.5.4) Antinuclear antibody (ANA) greater than 1:100 (indirect immunofluorescence, IIF). If ANA = 1:100, the investigator shall assess whether there is relevant medical history or symptoms of connective tissue disease or autoimmune disease.
- •Electrocardiogram showing clinically significant abnormalities at screening rendering the participant unsuitable for trial participation as judged by the investigator.
- •Autoimmune diseases including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis, autoimmune uveitis.
- •Significant systemic or severe diseases other than liver disease, including recent (≤ 6 months prior to screening) congestive heart failure (New York Heart Association (NYHA) Functional Classification III-IV), unstable coronary artery disease, arterial revascularization, respiratory diseases, renal insufficiency, stroke, transient ischemic attack, organ transplantation, psychiatric disorders. Uncontrolled systemic diseases: poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg); poorly controlled diabetes (fasting plasma glucose (FPG) greater than 10 mmol/L).
- •Major trauma or major surgery within 3 months prior to screening, or planned surgery during the study period.
- •Received any systemic anti-tumor therapy (including radiotherapy), immunosuppressive therapy (including biological immunosuppressants), or immunomodulatory therapy within 6 months prior to screening (including oral non-biological immunomodulatory agents such as methotrexate greater than 25 mg/week, azathioprine greater than 3 mg/kg/day, or 6-mercaptopurine greater than 1.5 mg/kg/day).
- •Received high-dose systemic corticosteroids within 3 months prior to screening, defined as prednisone ≥ 40 mg/day for more than 7 consecutive days or prednisone ≥ 20 mg/day for more than 14 consecutive days.
- •History of drug dependence or substance abuse.
- •History of excessive alcohol consumption. Excessive alcohol consumption is defined as weekly ethanol intake exceeding 210 g for males and 140 g for females over the past 12 months. Ethanol intake (g) = Volume consumed (mL) × Alcohol by volume (%) × 0.
- •History of allergy to the investigational product or its excipients.
- •Previous participation in clinical trials of hepatitis B core protein allosteric modulators (CpAMs).
- •Participated in other clinical trials of investigational drugs or medical devices and received study intervention within 3 months prior to screening.
- •Participants deemed inappropriate for enrollment by the investigator.
研究组 & 干预措施
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: Entecavir dispersible tablets (Drug)
TQA3605 Tablets + NAs
TQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
干预措施: TQA3605 tablets (Drug)
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: TQA3605 tablets Placebo (Drug)
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: Tenofovir Disoproxil Fumarate Tablets (Drug)
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: Tenofovir Amibufenamide Tablets (Drug)
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: TQA3605 tablets (Drug)
TQA3605 Tablets Placebo + NAs
TQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
干预措施: Tenofovir Alafenamide Fumarate Tablets (Drug)
TQA3605 Tablets + NAs
TQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
干预措施: Entecavir dispersible tablets (Drug)
TQA3605 Tablets + NAs
TQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
干预措施: Tenofovir Disoproxil Fumarate Tablets (Drug)
TQA3605 Tablets + NAs
TQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
干预措施: Tenofovir Alafenamide Fumarate Tablets (Drug)
TQA3605 Tablets + NAs
TQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
干预措施: Tenofovir Amibufenamide Tablets (Drug)
结局指标
主要结局
HBV DNA
时间窗: 48 weeks
Difference in the percentage of trial participants achieving HBV DNA less than 10 IU/mL after 48 weeks of treatment between the treatment group and the control group
次要结局
- HBV DNA(Baseline to week 104)
- HBsAg(Baseline to week 104)
- HBeAg(Baseline to week 104)
- Alanine aminotransferase(ALT)(Baseline to week 104)
- Virology breakthrough(Baseline to week 104)
- HBV markers(Baseline to week 104)
- Adverse events (AE)(From screening to Week 104)
- Steady state minimum concentration (Cmin,ss)(48 weeks)