Hepatitis B, Chronic
Conditions
Brief summary
This study is divided into two parts. Phase Ib is a randomized, double-blind, placebo-controlled trial, designed to evaluate the safety, tolerability, pharmacokinetic characteristics, preliminary efficacy, and immunogenicity of TQA3038 injection in patients with chronic hepatitis B. It is expected to include 72 subjects. Phase IIa adopted an open-label, randomized, parallel-controlled design, with a total of 90 subjects included, mainly evaluating the changes in serum HBsAg compared to baseline at the end of the 48th week.
Interventions
DRUGTQA3038 injection/placebo
TQA3038 is a Anti-Hepatitis B virus (HBV) drugs.
DRUGNucleotide drugs Control group
Nucleotide drugs are nucleoside reverse transcriptase inhibitors.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects voluntarily participate in this study and sign informed consent; * Male and female ≥18 years old and ≤65 years old; * Male subjects with a weight of ≥ 50 kilograms and female subjects with a weight of ≥ 45 kilograms, BMI 18\ 28 kg/m2; * Patients diagnosed with chronic hepatitis B (CHB) who have been serum HBsAg positive for more than 6 months and HBeAg positive ; During the screening period, 100 IU/ml ≤ HBsAg quantification ≤ 5000 IU/ml; * The subjects are able to communicate well with the researchers, voluntarily and can understand and follow the experimental protocol process to complete the study; * The subjects (including partners) are willing to voluntarily adopt effective contraceptive measures during the clinical trial period and long-term follow-up period, and specific contraceptive measures are shown in the appendix; * The treated patients need to meet the condition:The subject must have received oral nucleoside (acid) drug treatment and a stable treatment regimen; * Newly treated patients must meet the condition:During screening, the subjects had never received antiviral treatment for chronic hepatitis B B (oral nucleoside (acid) drugs and interferon), or had irregular antiviral treatment in the past, but had not received any antiviral treatment for chronic hepatitis B 3 months before enrollment.
Exclusion criteria
* Pregnant and lactating women; * Chronic diseases other than chronic HBV infection with significant clinical significance that have a history of mental illness or are deemed unsuitable by researchers for participation in this study; * Acute diseases with significant clinical significance occurring within 7 days prior to receiving the investigational drug; * Individuals with a history of active pathological bleeding or a tendency towards bleeding; * Prescription medication has been used within 14 days prior to receiving the study drug; * Receive any preventive or attenuated vaccines within 14 days prior to receiving the study drug; * Blood donors or those who have lost a significant amount of blood within the first 3 months of screening, or those who have donated blood during the planned study period; * Subjects with a history of excessive alcohol consumption; * A history of alcohol or drug abuse within the 12 months prior to screening, or a positive drug screening result during screening; * Complicated with other infected disease; * Patients with significant liver fibrosis or cirrhosis before or during screening; * History of chronic liver diseases other than chronic HBV infection; * Patients have a history of hepatocellular carcinoma (HCC) before or at the time of screening, or may be at risk for HCC; * Used immunosuppressive or immunomodulatory drugs and cytotoxic drugs within 6 months prior to the study medication; * During screening, subjects showed significant laboratory results abnormalities； * Screening for tumors with a history of malignancy within the first 5 years, excluding tumors that can be completely cured through surgical resection; * Uncontrollable chronic diseases; * History of intolerance to subcutaneous injection; * Participated in clinical studies of any drug or medical device within 3 months prior to drug administration or within 5 times the half-life of the investigational drug, or used the investigational drug; * Those considered unsuitable for enrollment by the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) | Baseline up to 16 weeks | The incidence of adverse events (AEs) during treatment. |
| Serious adverse events (SAEs) | Baseline up to 16 weeks | The incidence of serious adverse events (SAEs) during treatment. |
| Hepatitis B virus surface antigen (HbsAg) | Baseline up to 48 weeks | Changes of serum HbsAg compared with baseline at the 48th week of treatment in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution (Vd/F) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Volume of distribution (Vd/F) of TQA3038 in Plasma. |
| Apparent Plasma Clearance (CL/F) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Apparent Plasma Clearance (CL/F) of TQA3038 in Plasma. |
| Apparent Terminal Elimination Half-life (t1/2) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Apparent Elimination Half-life (T1/2) of TQA3038 in Plasma |
| Time to Reach Maximum Plasma Concentration (Tmax) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Time to reach Cmax of TQA3038 and its metabolite in plasma. |
| Incidence of Neutralization antibody (Nab) | Day1 before administration, Week 8, Week 16, and during withdrawal | Incidence of Neutralization antibody (Nab) in serum. |
| Hepatitis B surface antigen (HBsAg) | Baseline up to 48 weeks | Changes in Hepatitis B surface antigen (HbsAg) levels from baseline during the study period. |
| Hepatitis B E antigen (HBeAg) | Baseline up to 48 weeks | Changes in HbeAg levels from baseline during the study period. |
| The incidence and titer of anti drug antibodies (ADA) | Day1 before administration, Week 8, Week 16, and during withdrawal | The incidence and titer of anti drug antibodies (ADA) in serum. |
| Maximum Plasma Concentration (Cmax) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Maximum concentration of TQA3038 and its metabolite in plasma. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) | Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose | Area under the curve of TQA3038 and its metabolite from time 0 to last measurable time. |
Countries
China
Contacts
Primary ContactQin Ning, Doctor
Backup ContactJunqi Niu, Doctor
Outcome results
None listed