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
A Randomized, Double-Blind, Placebo-Controlled Phase III Trial With an Open-Label Extension to Evaluate the Efficacy and Safety of TQA3605 Tablets in Chronic Hepatitis B Virus-Infected Patients With Low-Level Viremia or Suboptimal Response After at Least 12 Months of NAs Therapy
1 other identifier
interventional
930
1 country
77
Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase III study with an open-label extension. The purpose is to evaluate efficacy and safety in adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy, to demonstrate that TQA3605 Tablets combined with oral nucleos(t)ide analogues can improve efficacy with satisfactory safety profile compared with oral nucleos(t)ide analogues alone in this population. Approximately 930 adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy are planned to be enrolled in this study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2026
Typical duration for phase_3
77 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 28, 2026
CompletedFirst Posted
Study publicly available on registry
September 1, 2026
CompletedStudy Start
First participant enrolled
September 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
October 2, 2026
July 1, 2026
2 years
August 28, 2026
September 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
HBV DNA
Difference in the percentage of trial participants achieving HBV DNA less than 10 IU/mL after 48 weeks of treatment between the treatment group and the control group
48 weeks
Secondary Outcomes (9)
HBV DNA
Baseline to week 104
HBV DNA
Baseline to week 104
HBsAg
Baseline to week 104
HBeAg
Baseline to week 104
Alanine aminotransferase(ALT)
Baseline to week 104
- +4 more secondary outcomes
Study Arms (2)
TQA3605 Tablets + NAs
EXPERIMENTALTQA3605 Tablets 100 mg once daily (QD) plus NAs administered for 96 weeks. Following completion of the 96-week treatment period, participants will continue NAs therapy with an 8-week follow-up.
TQA3605 Tablets Placebo + NAs
PLACEBO COMPARATORTQA3605 tablets placebo, once daily, combined with NAs for 48 weeks. After the 48-week double-blind period, all trial participants received TQA3605 tablets, 100mg each time, QD, combined with NAs for another 48 weeks. After the 96-week treatment, NAs treatment was continued for an 8-week follow-up
Interventions
TQA3605 tablets are core protein allosteric modulators
Entecavir dispersible tablets are a type of nucleoside analog antiviral drug.
Tenofovir Disoproxil Fumarate (TDF) is a nucleoside reverse transcriptase inhibitor.
Tenofovir Alafenamide Fumarate (TAF) is a nucleoside reverse transcriptase inhibitor.
Tenofovir Amibufenamide (TMF) is a phosphoramidate prodrug of tenofovir and belongs to nucleos(t)ide reverse transcriptase inhibitors.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- Pregnant women (positive pregnancy test) or breastfeeding women.
- 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 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).
- 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).
- 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.
- Electrocardiogram showing clinically significant abnormalities at screening rendering the participant unsuitable for trial participation as judged by the investigator.
- Autoimmune diseases including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, psoriasis, autoimmune uveitis.
- 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).
- 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 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (77)
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230001, China
The First Affiliated Hospital of Ustc（Anhui Provincial Hospital）
Hefei, Anhui, 230001, China
The First Affiliated Hospital of Wannan Medical College / Yijishan Hospital of Wannan Medical College
Wuhu, Anhui, 241001, China
Beijing Ditan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100000, China
Peking University First Hospital
Beijing, Beijing Municipality, 100010, China
Beijing Youan Hospital，Capital Medical University
Beijing, Beijing Municipality, 100069, China
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010, China
The Southwest Hospital of Amu
Chongqing, Chongqing Municipality, 400038, China
Chongqing University Three Gorges Hospital
Chongqing, Chongqing Municipality, 404000, China
Mengchao Hepatobiliary Hospital of Fujian Medical University
Fuzhou, Fujian, 350007, China
Zhongshan Hospital, Xiamen University
Xiamen, Fujian, 361004, China
The First Hospital of Lanzhou University
Lanzhou, Gansu, 730000, China
Gansu Wuwei Tumour Hospital
Wuwei, Gansu, 730000, China
Nanhai District People's Hospital of Foshan
Foshan, Guangdong, 528000, China
The Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510630, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518000, China
The Fifth Affiliated Hospital of Sun Yat-sen University
Zhuhai, Guangdong, 519000, China
Liuzhou Worker's Hospital
Liuzhou, Guangxi, 545000, China
Guizhou Provincial People's Hospital
Guiyang, Guizhou, 550002, China
Affiliated Hospital of Zunyi Medical University
Zunyi, Guizhou, 563000, China
Hainan Provincial People's Hospital
Haikou, Hainan, 570311, China
Hebei Petro China Central Hospital
Langfang, Hebei, 065000, China
Shijiazhuang Fifth Hospital
Shijiazhuang, Hebei, 050024, China
The Fourth Hospital of Harbin Medical University
Harbin, Heilongjiang, 150000, China
Harbin Medical University, The Second Affiliated Hospital
Harbin, Heilongjiang, 150001, China
Mudanjiang Kang'an Hospital
Mudanjiang, Heilongjiang, 157011, China
Anyang People's Hospital
Anyang, Henan, 455000, China
Luoyang Central Hospital（Luoyang Central Hospital Affiliated to Zhengzhou University）
Luoyang, Henan, 471000, China
Puyang People's Hospital
Puyang, Henan, 457000, China
The Sixth People's Hospital of Zhengzhou
Zhengzhou, Henan, 450000, China
The first affiliated hospital of Zhengzhou university
Zhengzhou, Henan, 450052, China
Jingzhou Central Hospital
Jingzhou, Hubei, 434036, China
Second Xiangya Hospital of Central South University
Changsha, Hunan, 410125, China
The First Affiliated Hospital Of University Of South China
Hengyang, Hunan, 421001, China
The General Hospital of Hunan University of Medicine
Huaihua, Hunan, 418000, China
Chifeng Hospital
Chifeng, Inner Mongolia, 024000, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210000, China
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008, China
The Fifth People's Hospital of Suzhou
Suzhou, Jiangsu, 215100, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 333000, China
Hepatobiliary Hospital of Jilin Province
Changchun, Jilin, 130000, China
The Second Hospital of Jilin University
Changchun, Jilin, 130000, China
The first hospital of Jilin University
Changchun, Jilin, 130400, China
Dalian Public Health Clinical Center
Dalian, Liaoning, 116021, China
The Sixth People's Hospital of Shenyang
Shenyang, Liaoning, 110002, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110022, China
The 4'th People's Hospital of Qinghai Province
Xining, Qinghai, 810000, China
Bao Ji City People's Hospital （BaoJi Emergency Medical Center ）
Baoji, Shaanxi, 722300, China
The First Affiliated Hospital of Xi'an Jiao Tong University
Xi'an, Shaanxi, 710000, China
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710000, China
Shandong Public Health Clinical Center
Jinan, Shandong, 250100, China
Liaocheng People's Hospital
Liaocheng, Shandong, 252000, China
Qingdao Municipal Hospital
Qingdao, Shandong, 266011, China
Weifang People's Hospital
Weifang, Shandong, 261000, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200000, China
Shanghai East Hospital
Shanghai, Shanghai Municipality, 200120, China
Shanghai Pudong Hospital
Shanghai, Shanghai Municipality, 200120, China
Shanghai Pudong New Area Gongli Hospital
Shanghai, Shanghai Municipality, 200135, China
Shanghai Sixth People's Hospital
Shanghai, Shanghai Municipality, 200233, China
Changzhi People's Hospital
Changzhi, Shanxi, 046000, China
Shanxi province fenyang hospital
Lüliang, Shanxi, 032209, China
Shanxi Provincial People's Hospital
Taiyuan, Shanxi, 030000, China
Yuncheng Central Hospital
Yuncheng, Shanxi, 044000, China
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610000, China
Public Health Clinical Center of Chengdu
Chengdu, Sichuan, 610066, China
Deyang People's Hospital
Deyang, Sichuan, 618000, China
Meishan People's Hospital
Meishan, Sichuan, 620000, China
Tianjin First Central Hospital
Tianjin, Tianjin Municipality, 300380, China
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830063, China
The Fourth Affiliated Hospital of Xinjiang Medical University (Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region)
Ürümqi, Xinjiang, 830063, China
The First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650032, China
The First Affiliated Hospital Zhejiang University School Of Medicine
Hangzhou, Zhejiang, 310006, China
Lishui People's Hospital
Lishui, Zhejiang, 323000, China
The Second Hospital of Ningbo
Ningbo, Zhejiang, 315010, China
Taizhou Hospital Of Zhejiang Province
Taizhou, Zhejiang, 318000, China
Ruian People's Hospital
Wenzhou, Zhejiang, 325200, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2026
First Posted
September 1, 2026
Study Start
September 1, 2026
Primary Completion (Estimated)
September 1, 2028
Study Completion (Estimated)
October 1, 2029
Last Updated
October 2, 2026
Record last verified: 2026-07