Study of GST-HG131&141 Tablets Compared With Placebo in Patients With Chronic Hepatitis B

Official title

A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Safety and Efficacy of GST-HG131/ GST-HG141 Tablets in Patients With Chronic Hepatitis B

Overview

A randomized, double-blind, placebo-controlled Phase IIa clinical study to evaluate the safety and efficacy of GST-HG131/GST-HG141 tablets in patients with chronic hepatitis B

Interventions

• Drug GST-HG141
  GST-HG141 is a novel, potent and selective HBV CAM, which has a distinct molecular mechanism of its antiviral action compared to other CAMs reported in the literature, and has demonstrated strong antiviral properties in pre-clinical studies in vitro and in vivo.
• Drug GST-HG131
  GST-HG131 is a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals.
• Drug GST-HG141 Placebo
  GST-HG141 Placebo

Primary outcome measures

• HBsAg decline from baseline at D168 [Time frame: : Baseline and up to 168 days]

Eligibility criteria

Inclusion criteria

• Able to sign the informed consent form and fully understand the test content, process and possible adverse reactions.
• Males and females aged 35-65 years(inclusive),able to complete research in accordance with test plan requirements.
• Participants who have no childbearing plan in a year,and must agree to voluntarily use the contraceptive methods specified in the protocol from screening to 6 months after the last dose of the study.
• Male body weight ≥ 50 kg, female body weight ≥ 45 kg, with a body mass index (BMI) of 18-30 kg/m2 (inclusive).
• Participants who have received stable NA therapy for more than half a year， and have maintained the NA regimen for ≥3 months prior to Screening.
• HBV DNA concentration must be adequately suppressed, defined as At least two tests within 28 days of the screening period (more than 1 week apart) with HBV DNA lower than LLOQ .
• HBeAg negative, 100≤HBsAg ≤1500 IU/mL, serum Alanine aminotransferase (ALT)<1×upper limit of normal(ULN) during screening.
• Able to communicate well with clinical staff and complete the trial according to protocol requirements.

Exclusion criteria

• Participants with a history of allergy to any component of the investigational product, or allergic diathesis (allergies to multiple drugs and foods).
• Participants unable to tolerate venous blood collection, or with a history of needle syncope or blood phobia.
• Participants who sustained major trauma or underwent major surgery within 3 months prior to screening, or those planning to undergo surgery during the study period.
• Participants with a history of alcohol abuse (defined as alcohol intake >14 standard units per week; one standard unit equals 350 mL beer, 120 mL wine, or 30 mL spirits with 40% alcohol by volume) or drug abuse/dependence at screening.
• Participants who participated in a clinical trial of any medicinal product or medical device (excluding in vitro diagnostic reagents) and received the investigational product or device within 3 months prior to study drug administration.
• Participants who received any anti-hepatitis B medications other than nucleos(t)ide analogues (NUCs), including marketed and unapproved agents, within 6 months prior to study drug administration.
• Participants who received immunosuppressants, immunomodulators (thymosin, interferons) or cytotoxic drugs within 6 months before study drug administration; or patients who received live attenuated vaccines or live vaccines within 1 month prior to screening.
• Participants with clinically significant acute or chronic liver disease unrelated to HBV infection (non-alcoholic fatty liver disease shall be assessed by the investigator for exclusion eligibility).
• Participants with a medical history of liver cirrhosis or progressive liver fibrosis, defined as: liver histopathology confirming cirrhosis; endoscopy showing esophageal and gastric varices; or liver stiffness measurement (LSM) ≥9.0 kPa on transient elastography at screening.
• Participants with confirmed or suspected decompensated HBV-related cirrhosis, including but not limited to hepatic encephalopathy, hepatorenal syndrome, variceal bleeding of esophagus and stomach, splenomegaly, ascites, and primary liver cancer.
• Participants with concurrent malignant tumors or a history of other malignancies within 5 years prior to screening (excluding cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix); participants complicated with unstable cardiovascular and cerebrovascular diseases, uncontrolled diabetes (glycated hemoglobin >7%), refractory hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg, deemed ineligible by the investigator for study participation), or other relevant comorbidities.
• Participants judged by the investigator to have gastrointestinal impairment or disorders that may interfere with oral drug absorption, including severe gastrointestinal diseases (peptic ulcer, erosive or atrophic gastritis), partial gastrectomy, or gastrointestinal symptoms graded >Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) at screening (e.g., nausea, vomiting, diarrhea).
• Participants with suspected or confirmed acute or chronic infection within 2 weeks prior to randomization.
• Abnormal laboratory parameters meeting any of the following thresholds:

Platelet count <100×10⁹/L; White blood cell count <3.0×10⁹/L; Absolute neutrophil count <1.3×10⁹/L; Serum total bilirubin >2× upper limit of normal (ULN); Serum albumin <35 g/L; Creatinine clearance ≤60 mL/min (calculated via the CKD-EPI equation); International normalized ratio (INR) of prothrombin time >1.5.

• Participants with alpha-fetoprotein (AFP) >50 µg/L or imaging suggestive of suspected malignant hepatic space-occupying lesions.
• Participants positive for hepatitis C virus antibody (HCV-Ab); positive for Treponema pallidum antibody (TP-Ab) with positive rapid plasma reagin (RPR) test; or positive for human immunodeficiency virus antibody (HIV-Ab).
• Female participants with positive serum pregnancy test at screening or baseline, or breastfeeding women.
• Any other conditions deemed by the investigator to impair the participant's ability to provide informed consent or comply with the study protocol; participants judged unsuitable for trial participation; or circumstances where participation may compromise trial integrity or personal safety.

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 · 1 center

• Beijing Friendship Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07709520 · GST-HG131&141-II-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗