Chronic Hepatitis B
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled phase II study, in which all participants are required to use TQA3605 tablets/placebo in combination with entecavir. The purpose is to evaluate the efficacy and safety of TQA3605 tablets combined with entecavir in treatment-naive chronic HBV-infected subjects. A total of 215 subjects are required.
Interventions
Placebo contains no active substance.
DRUGTQA3605 Tablets
TQA3605 tablets is core protein allosteric modulators
Entecavir dispersible tablets is an inhibitor of hepatitis B virus replication.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years old (including boundary values), regardless of gender; * Screening requires virological , clinical or pathological evidence of hepatitis B virus infection for more than 6 months; HBsAg positive, HBeAg positive, ALT≤5×ULN at screening; * Never received nucleoside (acid) analog or interferon treatment, or previously received no more than 12 weeks of treatment but had discontinued therapy at least 6 months prior to the screening visit; * Ability to communicate effectively with researchers and understand and comply with the requirements of this study, understand and sign the informed consent form; * Male subjects with female partners who have fertility or female subjects of childbearing age are willing to voluntarily adopt effective contraceptive measures screening to within 3 months after leaving the group.
Exclusion criteria
* Pregnant (positive pregnancy test) or lactating women. * Co-infection with other viruses such as Hepatitis A Virus (HAV), Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), Hepatitis E Virus (HEV), Human Immunodeficiency Virus (HIV), Syphilis, etc.; * History of cirrhosis or evidence of significant fibrosis or cirrhosis before or during screening; * History of hepatocellular carcinoma (HCC) or suspected HCC before or during screening.; * History of malignant tumors within the past 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, Wilson's disease, Gilbert syndrome, etc; * Previous organ or bone marrow transplantation; * Clinically significant abnormal laboratory test results at screening. * Poorly controlled thyroid diseases or clinically significant thyroid dysfunction; * Autoimmune diseases; * Significant systemic or major illnesses other than liver disease. * Any systemic anti-tumor or immunosuppressive therapy, or immunomodulatory therapy within 6 months prior to screening. * High-dose systemic corticosteroids use within 3 months prior to screening; * History of alcohol or drug abuse within the past year or excessive alcohol consumption. * History of blood transfusion within 2 months prior to screening; * History of allergy to investigational drug or its excipients. * Previously participated in the clinical trial of hepatitis B core protein allosteric modulators; * Participation in another clinical trial and receipt of an investigational drug within the following timeframes before the first dose in this study: 5 half-lives (if known) or twice the duration of the biological effect of the study treatment (if known), whichever is longer, or 90 days (if the half-life or duration is unknown); * History or condition of cardiovascular disease; * Any other condition deemed inappropriate for inclusion by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| hepatitis B virus (HBV) DNA <10 IU/mL | 48 weeks | Percentage of subjects with HBV DNA below the lower limit of quantification (\<10 IU/mL) after 48 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of HBV DNA<20 IU/mL | 12 weeks, 24 weeks, 36 weeks, 48weeks, 60 weeks, 72 weeks | Percentage of subjects with HBV DNA\<20 IU/mL at weeks 12, 24, 36, 48, 60, and 72 of treatment. |
| Percentage of subjects with HBeAg serologic clearance and/or serologic conversion | 24weeks, 48 weeks, 72 weeks | Percentage of subjects with HBeAg serologic clearance and/or serologic conversion |
| Alanine aminotransferase(ALT)≤The upper limit of the normal reference value (ULN) | 24weeks, 48 weeks, 72 weeks | The rate of ALT normalization at weeks 24, 48, and 72 of treatment |
| Percentage of subjects with HBV DNA<10 IU/mL | 12 weeks, 24 weeks, 36 weeks, 60 weeks, 72 weeks | Percentage of subjects with HBV DNA\<10 IU/mL at week 12, 24, 36, 60, and 72 |
| Actual values of HBV markers and changes over time relative to baseline | 12 weeks, 24 weeks, 36 weeks, 48 weeks, 72 weeks | Actual values of HBsAg, HBeAg, HBV DNA, HBV RNA, and Hepatitis B core-related antigen (HBcrAg) at each visit time point and their changes over time relative to baseline. |
| Adverse events (AE) | 72 weeks | The incidence and severity of adverse events. |
| Steady state minimum concentration (Cmin,ss) | 48 weeks | Cmin,ss of TQA3605 and its metabolite |
| Virology breakthrough percentage | 24weeks, 48 weeks, 72 weeks | Percentage of subjects who experienced virological breakthroughs at weeks 24, 48, and 72 of treatment |
Countries
China
Outcome results
None listed