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

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

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

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: TQA3810 tablets+NUC; Drug: Placebo+NUC

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanyan Yu, Doctor; Phone Number: 13901194223; Email: yyy@bjmu.edu.cn
• Study Contact Backup: Name: Jun Li, Doctor; Phone Number: 13905175333; Email: dr-lijun@vip.sina.com

Study Locations

• China
  • Gansu
    • Wuwei, Gansu, China, 733099
      • Not yet recruiting
      • Gansu Wuwei Tumour Hospital
      • Contact: Wenhua Zhang, Bachelor; Phone Number: 18993531188; Email: 925944468@qq.com
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Not yet recruiting
      • Zunyi Medical University Affiliated Hospital
      • Contact: Yawen Luo, Master; Phone Number: 18908523636; Email: luoyw719@163.com
  • Jiangsu
    • Nanjing, Jiangsu, China, 210031
      • Not yet recruiting
      • Nanjing Drum Tower Hospital
      • Contact: Jie Li, Doctor; Phone Number: 15863787910; Email: lijier@sina.com
    • Suzhou, Jiangsu, China, 215131
      • Not yet recruiting
      • The Fifth People's Hospital of Suzhou
      • Contact: Chuanwu Zhu, Doctor; Phone Number: 13606202525; Email: zhuchw@126.com
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Not yet recruiting
      • Shenyang Sixth People's Hospital
      • Contact: Fang Yang, Doctor; Phone Number: 18502460760; Email: yangf0301@163.com
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University
      • Contact: Feng Ye, Doctor; Phone Number: 18991232860; Email: Yefeng.jiaotong@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: TQA3810 tablets+NUC; 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.	Drug: TQA3810 tablets+NUC; TQA3810 is a novel, effective and highly selective small-molecule oral Toll-like receptors-8 agonist.
Placebo Comparator: Part A: Placebo+NUC; Part A: Placebo+NUC: Placebo combined with oral nucleoside (acid) drugs (NUC) group was treated for 24 weeks.	Drug: Placebo+NUC; NUC: Entecavir Dispersible Tablets, Inhibit viral replication; Tenofovir Disoproxil Fumarate Tablets, Nucleotide reverse transcriptase inhibitors; Tenofovir Alafenamide Fumarate Tablets, Inhibit HBV replication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during the study period	The study required collection of any adverse medical events, whether causally associated with the investigational drug or not, from the time the subject signed the informed consent to 28 days after the end of study medication or the initiation of other anti-HBV therapy (whichever came first).	Up to 52 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum HBsAg	Changes in serum HBsAg from baseline at 24 weeks	24 weeks
HBV DNA level changes and drug resistance monitoring	Changes in HBV DNA levels from baseline and drug resistance monitoring.	24 weeks
HBeAg level change	Changes in HBeAg levels from baseline.	24 weeks
HBsAg clearance and/or serological conversion	Percentage of subjects with HBsAg clearance and/or serological conversion.	24 weeks
HBeAg clearance and/or serological conversion	Percentage of subjects with HBeAg clearance and/or serological conversion	24 weeks
HBsAg level decreased by ≥0.5log10 IU/ml	Proportion of subjects with HBsAg levels decreased at least 0.5log10 IU/ml	24 weeks
Changes of HBV RNA and hepatitis B core-related antigen (HBcrAg) levels during treatment	Changes of HBV RNA and HBcrAg levels from baseline during treatment	24 weeks
Peak time (Tmax)	Time to peak blood concentration after a single dose.	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
Peak Concentration	The highest plasma drug concentration that can be achieved after medication.	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
Area under blood concentration-time curve (AUC)	The amount of drug absorbed into the human circulation after a single dose can be estimated using the area under the blood concentration-time curve.	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
Apparent volume of distribution (Vd/F)	When a drug reaches homeostasis in the body, the ratio of the amount of drug in the body to the blood concentration is called the apparent volume of distribution.	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
Plasma clearance	How many milliliters of plasma can the kidneys completely clear in unit time (per minute).	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
Elimination half-life time	The time it takes for the plasma concentration to drop by half	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
Peaking Time	The time required to reach peak steady-state concentration after administration.	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
Steady state maximum concentration	The highest blood concentration that occurs After stabilization	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
Steady state minimal concentration	The lowest blood concentration that occurs after stabilization.	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
Area under steady-state blood concentration-time curve	The area under the curve obtained with blood drug concentration as the vertical axis and time as the horizontal axis after administration.	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
Evaluate whether TQA3810 will affect the heart rate-corrected QT interval (QTc) of newly treated/treated chronic hepatitis B patients	Evaluate whether TQA3810 will affect the QTc interval of newly treated/treated chronic hepatitis B patients	24 weeks
Pharmacodynamic characteristics (IFN-γ, IL-1RA, CCL2, CCL4, CCL8, CCL11, CCL20, CXCL8, IL-12p70, IL-12p40, TNF-α, CRP)	Characteristics of IFN-γ, interleukin-1 receptor antagonist (IL-1RA), chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligands 4 (CCL4) , Chemokine (C-C motif) ligands 8 (CCL8), Chemokine (C-C motif) ligands 11 (CCL11), Chemokine (C-C motif) ligands 20 (CCL20), C-X-C motif chemokine ligand 8 (CXCL8), IL-12p70, IL-12p40, Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)	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

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: TQA3810-IIa-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No