A Clinical Study to Evaluate the Efficacy of TQA3038 Injection in Patients With Chronic Hepatitis B

Official title

A Phase Ib/IIa Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic, and Antiviral Efficacy of TQA3038 Injection in Patients With Chronic Hepatitis B

Overview

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

• Drug TQA3038 injection/placebo
  TQA3038 is a Anti-Hepatitis B virus (HBV) drugs.
• Drug Nucleotide drugs Control group
  Nucleotide drugs are nucleoside reverse transcriptase inhibitors.

Primary outcome measures

• Adverse events (AEs) [Time frame: Baseline up to 16 weeks]
• Serious adverse events (SAEs) [Time frame: Baseline up to 16 weeks]
• Hepatitis B virus surface antigen (HbsAg) [Time frame: Baseline up to 48 weeks]

Secondary outcome measures (10)

• Time to Reach Maximum Plasma Concentration (Tmax) [Time frame: 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 Plasma Concentration (Cmax) [Time frame: 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 Plasma Concentration Versus Time Curve (AUC) [Time frame: 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) [Time frame: 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) [Time frame: 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 Terminal Elimination Half-life (t1/2) [Time frame: 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]
• The incidence and titer of anti drug antibodies (ADA) [Time frame: Day1 before administration, Week 8, Week 16, and during withdrawal]
• Incidence of Neutralization antibody (Nab) [Time frame: Day1 before administration, Week 8, Week 16, and during withdrawal]
• Hepatitis B surface antigen (HBsAg) [Time frame: Baseline up to 48 weeks]
• Hepatitis B E antigen (HBeAg) [Time frame: Baseline up to 48 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 22 centers

• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• Mengchao Hepatobiliary Hospital of Fujian Medical University — Fuzhou
• Gansu province people hospital — Lanzhou
• The Third Affiliated Hospital of Sun Yat sen University — Guangzhou
• The First Affiliated Hospital of GUANGXI Medical University — Nanning
• Guizhou Provincial People's Hospital — Guiyang
• The Fourth Affiliated Hospital of Harbin Medical University — Harbin
• Shiyan City Taihe Hospital — Shiyan
• … and 14 more centers

Identifiers

NCT: NCT06452693 · TQA3038-Ib/IIa-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗