Chronic Hepatitis b
Conditions
Brief summary
A randomized, double-blind Phase Ib/IIa multicenter trial design was used. All eligible subjects received TQA3605 tablets/placebo plus nucleoside (acid) analogues. A total of 88 subjects were required
Interventions
DRUGPlacebo
TQA3605 placebo tablets were orally administered on an empty stomach (at least 2 hours before or after meals) with warm.
DRUGTQA3605 tablets
TQA3605 inhibits viral replication.
Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.
DRUGTenofovir disoproxil fumarate tablet
Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.
DRUGTenofovir alafenamide fumarate tablet
Tenofovir alafenamide fumarate inhibits 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 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects voluntarily participate in this study and sign informed consent; * Male and female, ≥18 years old and ≤70 years old (subject to the date of signing the informed consent); * Patients diagnosed with chronic hepatitis B (CHB) who have been serum HBsAg positive for more than 6 months and HBeAg positive or negative ; * The liver fibrosis ultrasound transient imaging elastic technology (Fibroscan/FibroTouch) showed that the liver hardness (LSM) was less than 12.4 Kpa; * Patients with chronic hepatitis B after treatment; * Treatment-naïve patients of chronic hepatitis B patients;
Exclusion criteria
* Complicated with other infected disease such as hepatitis A virus (HAV), hepatitis C virus (HCV), Hepatitis D virus (HDV), hepatitis E virus (HEV), human immunodeficiency virus (HIV), syphilis (syphilis antibody positive and need treatment determined by the investigator); * Abdominal ultrasound or other imaging or histology showed suspected cirrhosis or other liver disease before or during screening; * Patients have a history of hepatocellular carcinoma (HCC) before or at the time of screening, or may be at risk for HCC; * Active autoimmune disease diagnosed with immunodeficiency or undergoing systemic therapy which was continuing within 2 weeks before first dosing; * Currently being treated with nephrotoxic drugs or drugs that alter renal excretion; * Abnormal thyroid function; * Renal diseases such as chronic kidney disease and renal insufficiency or creatinine clearance (CLCr) \<60 ml/min during the screening period; * Hematologic and biochemical abnormalities; * History of allergy to the investigational drug or its excipients; * Recipients of solid organs or bone marrow transplants; * A history of malignant tumors within the past 5 years; * Interstitial lung disease, acute lung disease, etc.; * Uncontrolled systemic diseases such as high blood pressure and diabetes; * Have used any investigational drug or participated in a clinical trial within one month prior to the administration of study drug; * Those who received live attenuated vaccine within 28 days before the start of study treatment, inactivated vaccine within 7 days, or planned vaccination during the study period; * The investigator determines that there is any medical or psychiatric condition that puts the subject at risk, interferes with participation in the study, or interferes with the interpretation of the study results; * Female subjects that were pregnant, lactating or had a positive pregnancy result during the screening period or during the trial; Male and female patients with reproductive potential who were unwilling to use effective contraceptive methods during the study period; * Subjects who have any medical condition that may affect the absorption of oral drugs; * Within 12 weeks prior to screening, treated chronic hepatitis B patients who had stopped taking nucleoside (acid) analogues for more than 14 consecutive days; * Those considered unsuitable for enrollment by the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of serious adverse events (SAEs) | Up to 48 weeks | The severity of serious adverse events (SAEs) during treatment |
| The incidence of adverse events (AEs) | Up to 48 weeks | The incidence of adverse events (AEs) during treatment |
| Severity of adverse events (AEs) | Up to 48 weeks | The severity of adverse events (AEs) during treatment |
| Incidence of serious adverse events (SAEs) | Up to 48 weeks | The incidence of serious adverse events (SAEs) during treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis B e antigen | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | Changes in serum hepatitis B e antigen (HBeAg) from baseline |
| Serologic clearance and/or serologic conversion of HBsAg | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | Proportion of subjects with HBsAg serologic clearance and/or serologic conversion |
| Serologic clearance and/or serologic conversion of HBeAg | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | Proportion of subjects with HBeAg serologic clearance and/or serologic conversion |
| Virological breakthrough rate | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | The proportion of subjects who achieved a virological breakthrough (defined as a confirmed increase of HBV DNA levels \>1.0 log10 IU/ml from the minimum during treatment). |
| Peak time (Tmax) | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | Time to reach peak blood concentration after a single dose |
| Peak concentration | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The highest plasma drug concentration that can be achieved after medication |
| Incidence of abnormal laboratory test values | Up to 48 weeks | The incidence of abnormal laboratory values during treatment, e.g. triglycerides. |
| Apparent volume of distribution (Vd/F) | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | When a drug reaches homeostasis in the body, the ratio of the amount of drug in the body to the blood concentration is called the apparent volume of distribution. |
| Plasma clearance | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The amount of plasma that the kidneys completely clear in unit time (per minute). |
| Elimination half-life | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The time it takes for the plasma concentration to drop by half. |
| Steady state peak time | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The time required to reach peak steady-state concentration after administration |
| Steady state maximum concentration | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The highest blood concentration that occurs after stabilization |
| Steady state minimal concentration | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The lowest blood concentration that occurs after stabilization |
| Area under blood concentration-time curve (AUC) | pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10. | The amount of drug absorbed into the human circulation after a single dose can be estimated using the area under the blood concentration-time curve |
| Severity of abnormal laboratory test values | Up to 48 weeks | The severity of abnormal laboratory values during treatment, e.g. triglycerides. |
| Deoxyribonucleic acid level of hepatitis B virus | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | Changes in hepatitis B virus deoxyribonucleic acid (HBV DNA) levels from baseline |
| Hepatitis B surface antigen | At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study | Changes in serum hepatitis B surface antigen (HBsAg) from baseline |
Countries
China
Outcome results
None listed