Clinical trial NCT06644417: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HBV Infection With LLV
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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, 20 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.

Primary outcomes:
measure: HBV DNA (Hepatitis B virus Deoxyribonucleic Acid)
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence and severity of Adverse events (AEs)
timeFrame: 32 weeks
measure: Incidence and severity of serious adverse events (SAEs)
timeFrame: 32 weeks
measure: HBV DNA (<20 IU/mL)
timeFrame: Weeks 12, Weeks 16, Weeks 28, Weeks 32
measure: HBV DNA (<10 IU/mL)
timeFrame: Weeks 12, Weeks 16, Weeks 24, Weeks 28, Weeks 32
measure: Hepatitis B e antigen (HBeAg) Serology
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Alanine Aminotransferase (ALT) relapse rate
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Breakthroughs in virology
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Actual values and changes of HbsAg (Hepatitis B Surface Antigen)
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Actual values and changes of HBeAg
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Actual values and changes of HBV DNA
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: HBV RNA (Hepatitis B virus Ribonucleic Acid)
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: Actual values and changes of Human Hepatitis B virus core antigen - associated antigen (HbcrAg)
timeFrame: Weeks 12, Weeks 24, Weeks 32
measure: (Cmax, ss) Steady-state maximum concentration
timeFrame: Day 1, Day 29, Day 57, Day 85, Day 113, Day 169
measure: (Cmin, ss) Steady state minimum concentration
timeFrame: Day 1, Day 29, Day 57, Day 85, Day 113, Day 169
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical Universitybeijing Institute of Hepatology
state: Beijing
city: Fuzhou
country: China
facility: Meng Chao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Zunyi
country: China
facility: Zunyi Medical University Affiliated Hospital
state: Guizhou
city: Zhengzhou
country: China
facility: Zhengzhou No.6 peoples Hospital
state: Henan
city: Changsha
country: China
facility: The Second XIANGYA Hospital Of Central South University
state: Hunan
city: Yueyang
country: China
facility: Yueyang Central Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: The sixth people's Hospital Of Shenyang
state: Liaoning
city: Jinan
country: China
facility: Shandong Public Health Clinical Center
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong New District Gongli Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiao Tong University
state: Shanxi
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
city: Lishui
country: China
facility: Lishui People's Hospital
state: Zhejiang
Study officials:
References: