A Clinical Trial to Evaluate the Efficacy and Safety of TQA3810 Tablets in Combination/Non Combination With Nucleoside (Acid) Analogues in Patients With Primary/Treated Chronic Hepatitis B

CTTQ

Status and phase: Enrolling; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: TQA3810 tablets+NUC; Drug: Placebo+NUC

Study type: Interventional

Funder types: Industry

Identifiers

NCT06566248

TQA3810-IIa-01

Details and patient eligibility

About

To evaluate the efficacy and safety of combined/uncombined nucleoside (acid) analogues of TQA3810 tablets.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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).

Exclusion criteria

• 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 % × 0.8.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

90 participants in 2 patient groups, including a placebo group

Part A: TQA3810 tablets+NUC

Experimental group

Description:

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.

Treatment:

Drug: TQA3810 tablets+NUC

Part A: Placebo+NUC

Placebo Comparator group

Description:

Part A: Placebo+NUC: Placebo combined with oral nucleoside (acid) drugs (NUC) group was treated for 24 weeks.

Treatment:

Drug: Placebo+NUC