Clinical Study of TQA3605 Tablets Combined With Nucleoside (Acid) Analogs (NAs) Drugs Compared With NAs Drugs in the Treatment of Chronic Hepatitis B Virus (HBV) Infection

A Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of TQA3605 Tablets in Treated Subjects With Chronic HBV Infection With Low-level Viremia (LLV)

This study is a phase II multicenter, randomized, double-blind, placebo controlled study designed to evaluate the efficacy and safety in LLV subjects and demonstrate that TQA3605 tablets combined with oral NAs drugs can improve the efficacy and safety of LLV subjects compared with oral NAs drug.

Study Overview

• Status: Completed
• Conditions: HBV Infection With LLV
• Intervention / Treatment: Drug: TQA3605 Placebo plus NAs; Drug: TQA3605 tablets plus NAs

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100015
      • Beijing Ditan Hospital Capital Medical University
    • Beijing, Beijing Municipality, China, 100054
      • Beijing Youan Hospital, Capital Medical Universitybeijing Institute of Hepatology
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Meng Chao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Guizhou Provincial People's Hospital
    • Zunyi, Guizhou, China, 563000
      • Zunyi Medical University Affiliated Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Zhengzhou No.6 peoples Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • The Second Xiangya Hospital Of Central South University
    • Yueyang, Hunan, China, 414000
      • Yueyang Central Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Provincial People's Hospital
    • Suzhou, Jiangsu, China, 215131
      • The Fifth People's Hospital of Suzhou
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The First Affiliated Hospital of Nanchang University
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The Sixth People's Hospital of Shenyang
  • Shandong
    • Jinan, Shandong, China, 250102
      • Shandong Public Health Clinical Center
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai Municipality, China, 200336
      • Shanghai Tongren Hospital
  • Shanxi
    • Xi’an, Shanxi, China, 710000
      • The First Affiliated Hospital of Xi'an Jiao Tong University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • The First Affiliated Hospital Zhejiang University School Of Medicine
    • Lishui, Zhejiang, China, 323000
      • Lishui People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ages 18-65 (including boundary values), male or female.
• At the time of screening, etiological or clinical or pathological evidence of hepatitis B virus infection has been more than 1 year; HBsAg positive, 10 IU/mL <HBV DNA≤2000 IU/mL, ALT≤3×ULN (upper limit of normal); No obvious cirrhosis was found by the researchers.
• Continuous administration of any nucleoside (acid) analogues for more than 1 year and a stable regimen of ≥6 months prior to screening.
• Able to communicate well with researchers, understand and comply with the requirements of the study, understand and sign the informed consent.
• Male subjects with fertile female partners or female subjects of childbearing age were willing to voluntarily take effective contraceptive measures within 3 months after screening.

Exclusion Criteria:

• Pregnant (positive pregnancy test) or breastfeeding women.
• Co-infection with other viruses such as hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, human immunodeficiency virus, syphilis.
• A history of cirrhosis or evidence of significant fibrosis or cirrhosis at pre-screening/screening time.
• The subject had a history of hepatocellular carcinoma (HCC) before or at the time of screening, or was suspected of HCC.
• A history of malignant tumors within 5 years prior to screening, except for certain cancers that can be completely cured by surgical resection.
• Subjects with other chronic liver diseases, including but not limited to autoimmune liver disease, alcoholic liver disease, and hepatolenticular degeneration.
• Have previously received organ transplantation and bone marrow transplantation.
• Abnormal laboratory examination indicators that do not meet the requirements of the program during screening.
• Poorly controlled thyroid disease, or clinically significant thyroid dysfunction.
• Autoimmune diseases include but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis, autoimmune uveitis, etc.;
• In addition to liver disease, there are significant systemic or major diseases, including recent congestive heart failure, unstable coronary heart disease, arterial revasodilation, respiratory disease, digestive disease, renal insufficiency, stroke, transient ischemic attack, organ transplantation, psychiatric disease, etc. Uncontrolled systemic disease: poor blood pressure control; Diabetes has poor blood sugar control.
• Received any systemic antitumor (including radiation) or immunosuppressive therapy (including biological immune inhibitors), or immunomodulatory therapy (including non-biological immunomodulatory oral drugs) in the 6 months prior to screening.
• Receiving high doses of systemic corticosteroids within 3 months prior to the screening period.
• A history of alcohol and drug abuse within 1 year prior to the screening period.
• Blood transfusion ≤2 months before screening and/or blood donation ≤1 month before screening. Note: Participants were not allowed to donate blood throughout the study period.
• Have a history of allergy to the experimental drug or its excipients.
• Participated in clinical trials of hepatitis B core protein allosteric regulators.
• The subject has participated in a clinical trial and received the investigational drug during the period prior to the first administration of the study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days (if the half-life or duration is unknown).
• History or status of cardiovascular disease: history of risk factors for tip torsion ventricular tachycardia, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory tests. Family history of long QT syndrome or Brugada syndrome. The Electrocardiogram (ECG) showed clinically significant abnormalities. Heart Rate (HR)≤45 bpm.
• 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: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TQA3605 Placebo plus NAs; TQA3605 placebo plus NAs drug was administered for 24 weeks and NAs was continued until 32 weeks	Drug: TQA3605 Placebo plus NAs; Placebo without drug substance
Experimental: 100mg TQA3605 tablets plus NAs; 100mg TQA3605 tablets plus NAs drug was administered for 24 weeks and NAs was continued until 32 weeks	Drug: TQA3605 tablets plus NAs; TQA3605 tablets is core protein regulator
Experimental: 200mg TQA3605 tablets plus NAs; 200mg TQA3605 tablets plus NAs drug was administered for 24 weeks and NAs was continued until 32 weeks	Drug: TQA3605 tablets plus NAs; TQA3605 tablets is core protein regulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBV DNA (Hepatitis B virus Deoxyribonucleic Acid)	Percentage of subjects with HBV DNA below the lower limit of quantitative detection (<10 IU/mL) at 24 weeks of treatment	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse events (AEs)	The incidence and severity of AEs were determined by changes in physical examination, vital signs, electrocardiogram, and laboratory tests	32 weeks
Incidence and severity of serious adverse events (SAEs)	The incidence and severity of SAEs were determined by changes in physical examination, vital signs, electrocardiogram, and laboratory tests	32 weeks
HBV DNA (<10 IU/mL)	Percentage of subjects with HBV DNA below the lower limit of quantitative detection (<10 IU/mL)	Weeks 12, Weeks 16, Weeks 24, Weeks 28, Weeks 32
Hepatitis B e antigen (HBeAg) Serology	Percentage of subjects with HBeAg serologic clearance and/or serologic conversion (for HBeAg positive at baseline only)	Weeks 12, Weeks 24, Weeks 32
Alanine Aminotransferase (ALT) relapse rate	Renormalize ALT over time in subjects with baseline ALT>upper limit of normal (ULN) in the absence of enzyme-lowering Liver protection medicine	Weeks 12, Weeks 24, Weeks 32
Breakthroughs in virology	Percentage of subjects with a virological breakthrough	Weeks 12, Weeks 24, Weeks 32
HBV RNA (Hepatitis B virus Ribonucleic Acid)	Actual values and changes of HBV RNA over time relative to baseline	Weeks 12, Weeks 24, Weeks 32
(Cmax, ss) Steady-state maximum concentration	Steady-state maximum concentration of TQA3605	Day 1, Day 29, Day 57, Day 85, Day 113, Day 169
(Cmin, ss) Steady state minimum concentration	Steady-state minimum concentration of TQA3605	Day 1, Day 29, Day 57, Day 85, Day 113, Day 169
Actual values and changes of HbsAg (Hepatitis B Surface Antigen)	Actual values and changes of HbsAg over time relative to baseline	Weeks 12, Weeks 24, Weeks 32
Actual values and changes of HBeAg	Actual values and changes of HBeAg over time relative to baseline	Weeks 12, Weeks 24, Weeks 32
Actual values and changes of HBV DNA	Actual values and changes of HBV DNA over time relative to baseline	Weeks 12, Weeks 24, Weeks 32
Actual values and changes of Human Hepatitis B virus core antigen - associated antigen (HbcrAg)	Actual values and changes of HbcrAg over time relative to baseline	Weeks 12, Weeks 24, Weeks 32
HBV DNA (<10 IU/mL)	Percentage of subjects with HBV DNA below the lower limit of quantitative detection (<10 IU/mL)	Weeks 12, Weeks 16, Weeks 28, Weeks 32

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2024
• Primary Completion (Actual): August 25, 2025
• Study Completion (Actual): December 10, 2025

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; nas
• Other Study ID Numbers: TQA3605-II-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