Clinical trial NCT06706310: Evaluate TQ-A3334 Combined Nucleoside (Acid) Analogs in the First Treatment/Treatment of Chronic HBV Infection
Official title: Evaluate TQ-A3334 Tablets Combined Nucleoside (Acid) Analogs in the Initial Treatment/Chronic Hepatitis B Virus (HBV) Infection Subjects of Chronic HBV Infection
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: 2024-11-26
Enrollment: 116
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 uses random, double -blindness, placebo control, and phase multi -center test design. All subjects who meet the standards receive TQ-A3334 per tablet/placebo nucleoside (acid) analog. A total of 116 subjects are needed.


Eligibility criteria: Inclusion Criteria:

Those who meet all the selected standards below can enter the group test:

* The subject can communicate well with the researchers and understand and comply with the various items in this study, understand and sign the consent of informed consent;
* 18-65 years old (including the boundary value), and men and women are not limited (calculated based on the date of signing the consent of informedness);
* Serum virus standard: serum HBSAG positive for more than 6 months or more than 6 months chronic Evidence of HBV infection.
* No obvious liver cirrhosis is judged by researchers;

Those who have been treated after treatment need to meet the following conditions:

* The subject must receive oral nucleoside (acid) drug treatment before screening ≥6 months and the stable treatment plan before the screening period is ≥3 months;
* Historian history records of the HBV DNA \<6 and above HBV DNA \<6) HBV DNA \<minimum detection lower limit.

The initial governance subjects need to meet the following conditions:

* If the preliminary governance subject does not have HBSAG positive for 6 months, researchers can make the knot according to the initial diagnosis Fruit, the clinical manifestations of the subjects, and the comprehensive judgment of the family history of hepatitis B family whether it is chronic infection;
* The subjects have never received the treatment of chronic hepatitis B antiviral treatment (oral nucleoside drugs and interferon) at the time of screening;
* The upper limit of the normal reference value (ULN) \<Alanine aminotransferase≤ 5 × ULN (within 2 weeks before the first medication)

Exclusion Criteria:

Anyone who appears below will not be able to enter the group test:

* Pregnancy (pregnancy test is positive) or lactating women.
* Combined other virus infections such as hepatitis A virus，hepatitis C virus, hepatitis D virus, hepatitis E virus, human immunodeficiency virus, syphilis (those with positive syphilis antibodies, and those who are judged by researchers) and so on.
* History of liver cirrhosis or before screening/screening shows significant fibrosis or liver cirrhosis; or abdominal ultrasound examination prompts suspected liver cirrhosis; past liver dysfunction history or screening period has liver dysfunction compensation For those such as ascites, hepatic brain diseases, and esophageal stomach veins, bleeding;
* The subject of Hepatocellular Carcinoma (HCC) before screening or at the time of screening has a history of Hepatocellular Carcinoma (HCC), or suspected HCC;
* There is a history of malignant tumor diseases within the first 5 years of screening. Except for specific menstrual resection, it can be completely cured (such as skin basal cell carcinoma, etc.).
* A subject with other chronic liver diseases, including but not limited to autoimmune liver disease, alcoholic liver disease, hepatolenticular degeneration, etc.
* Organization and bone marrow transplantation have been accepted in the past.
* Poor thyroid disease, or clinical thyroid dysfunction (TSH abnormal T3 or T4 abnormalities);
* Eye disease: Including the bottom of the eye lesions (changes in the cotton samples with symptoms of the eye) and retinal lesions.
* Autoimmune diseases include but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, etc.
* In addition to liver disease, there are obvious systemic or major diseases.
* Any systemic anti -tumor (including radiation) or immunosuppressive treatment (including biomorphic inhibitors), or immunotherapies within 6 months before screening.
* Blood transfusion within ≤ 2 months before screening and/or donate blood within 1 month before screening. Note: The subject must not donate blood during the entire study;
* History of allergies to test medicines or its auxiliary materials;
* Toll-like receptors-7, Toll-like receptors-8 receptor agonist or PD-1, PD-L1 similar drugs have been used within three months before screening.
* The subject has participated in a clinical trial and accepted the test medicine for the test before the first time of the administration: 5 semi -half -life (such as known) or studying the duration of the biological effects (such as such as the duration of the biological effects (such as such as the duration of the biological effects (such as such as the duration of the biological effects (such as such as the duration of the biological effects (such as such as the duration of the biological effects (such as such as the duration of the biological effects (such as the duration of the biological effects (such as the duration of the biological effects (such as the duration of the biological effects (such as Two times (known) or 90 days (if the elderly prevails) or 90 days (if the half -life or duration is unknown).
* History or condition of cardiovascular disease: History of risk factors for risk factors of cutting -out rooms, including miracles, known long QT syndrome, heart failure, myocardial infarction, angina pectoris, or clinical significance laboratory Examination (including hypokalemia, hypercalcemia, or hypomagnesemia). Long QT syndrome or BRUGADA syndrome family history. ECG shows abnormal clinical significance. Heart rate≤45 Secondary/minutes.
* Researchers believe that those should not be included.

Primary outcomes:
measure: At 24 weeks, the changes in serum HBSAG relative to the baseline
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: The incidence of adverse events（AEs）
timeFrame: Up to 48 weeks
measure: Severity of adverse events (AEs)
timeFrame: Up to 48 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 48 weeks
measure: Severity of serious adverse events（SAEs）
timeFrame: Up to 28 weeks
measure: HBsAg<100 IU/ml and HBV DNA <20 IU/ml subject
timeFrame: Week 24, 48 weeks, 60 weeks, 72 weeks
measure: HBSAG self -based lines drop ≥0.5, ≥1 Log10IU/ml
timeFrame: Week 24, 48 weeks, 60 weeks, 72 weeks
measure: The proportion of subjects of HBSAG serological removal and/or serum transformation during the study period
timeFrame: Week 24, 48 weeks, 60 weeks, 72 weeks
measure: The proportion of subjects of HBEAG serological removal and/or serum conversion during the study period
timeFrame: Week 24, 48 weeks, 60 weeks, 72 weeks
measure: Peak time (Tmax)
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Peak Concentration
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Area under blood concentration-time curve (AUC)
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Apparent volume of distribution (Vd/F)
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Plasma clearance
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, D15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, D57 and D85 0hour pre-dose.
measure: Elimination half-life time
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Peaking Time
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, D15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, D57 and D85 0hour pre-dose.
measure: Steady state maximum concentration
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Steady state minimal concentration
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
measure: Area under steady-state blood concentration-time curve
timeFrame: Day1 0 hour pre-dose,10,20,30minutes,1,2,3,6,12,24,48 hours after dose, Day15 within 60 minutes pre-dose, Day29 0h pre-dose,10, 20, 30 minutes, 1,2,3,6,12,24,48 hours after dose, Day57 and Day85 0hour pre-dose
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Hospital workers in Liuzhou
state: Guangxi
city: WuHan
country: China
facility: WuHan Jinyintan Hospital
state: Hubei
city: Changsha
country: China
facility: The Second XIANGYA Hospital Of Central South University
state: Hunan
city: Wuxi
country: China
facility: The Fifth People's Hospital of Wuxi (Affiliated Wuxi Fifth Hospital of Jiangnan University)
state: Jiangsu
city: Changchun
country: China
facility: The first hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiao Tong University
state: Shaanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: First People's Hospital of Yunnan Province
state: Yunnan
city: Pu'er
country: China
facility: Pu'er People's Hospital
state: Yunnan
city: Rui'an
country: China
facility: People's Hospital Of RuiAn City
state: Zhejiang
Study officials:
References: