Clinical trial NCT06566248: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during the study period
timeFrame: Up to 52 months
Secondary outcomes:
measure: Changes in serum HBsAg
timeFrame: 24 weeks
measure: HBV DNA level changes and drug resistance monitoring
timeFrame: 24 weeks
measure: HBeAg level change
timeFrame: 24 weeks
measure: HBsAg clearance and/or serological conversion
timeFrame: 24 weeks
measure: HBeAg clearance and/or serological conversion
timeFrame: 24 weeks
measure: HBsAg level decreased by ≥0.5log10 IU/ml
timeFrame: 24 weeks
measure: Changes of HBV RNA and hepatitis B core-related antigen (HBcrAg) levels during treatment
timeFrame: 24 weeks
measure: Peak time (Tmax)
timeFrame: 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
measure: Peak Concentration
timeFrame: 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
measure: Area under blood concentration-time curve (AUC)
timeFrame: 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
measure: Apparent volume of distribution (Vd/F)
timeFrame: 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
measure: Plasma clearance
timeFrame: 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
measure: Elimination half-life time
timeFrame: 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
measure: Peaking Time
timeFrame: 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
measure: Steady state maximum concentration
timeFrame: 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
measure: Steady state minimal concentration
timeFrame: 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
measure: Area under steady-state blood concentration-time curve
timeFrame: 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
measure: Evaluate whether TQA3810 will affect the heart rate-corrected QT interval (QTc) of newly treated/treated chronic hepatitis B patients
timeFrame: 24 weeks
measure: Pharmacodynamic characteristics (IFN-γ, IL-1RA, CCL2, CCL4, CCL8, CCL11, CCL20, CXCL8, IL-12p70, IL-12p40, TNF-α, CRP)
timeFrame: 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
Other outcomes:
Locations:
city: Wuwei
country: China
facility: Gansu Wuwei Tumour Hospital
state: Gansu
city: Zunyi
country: China
facility: Zunyi Medical University Affiliated Hospital
state: Guizhou
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
city: Shenyang
country: China
facility: Shenyang Sixth People's Hospital
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
Study officials:
References: