Clinical Trial of TQA3605 Tablet in Combination With Nucleos(t)Ide Analogues(NAs) Versus NAs Alone for the Treatment of Patients With Chronic Hepatitis B Virus Infection Who Have Undergone Treatment and Exhibit Low Viral Load or Poor Response

Korábbi kezelés

• 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).
• 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 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.

Más betegség

• 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 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).
• Autoimmune diseases including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis, autoimmune uveitis.
• 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 (%) × 0.8.

Laborértékek

• 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.
• 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).

Egyéb

• Pregnant women (positive pregnancy test) or breastfeeding women.
• Electrocardiogram showing clinically significant abnormalities at screening rendering the participant unsuitable for trial participation as judged by the investigator.
• Participants deemed inappropriate for enrollment by the investigator.

• 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.