Study of the Efficacy and Safety of HS-10234 in Patients With Chronic Hepatitis B Virus Infection
Chronic HBV Infection
About this trial
This is an interventional treatment trial for Chronic HBV Infection focused on measuring HBeAg-positive or negative
Eligibility Criteria
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
- Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.
- Male and non-pregnant, non-lactating females, from 18 up to 65 years of age (based on the date of the screening visit). A negative serum pregnancy test at screening is required for female subjects of childbearing potential.
- Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).
- HBeAg-positive or HBeAg-negative chronic hepatitis B with all of the following: HBV DNA ≥ 2 x 104 IU/mL; Screening serum 1 ULN < ALT level ≤ 10 ULN.
- Treatment-naive subjects (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue) OR treatment-experienced subjects (defined as subjects meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue) will be eligible for enrollment. Treatment-experienced subjects receiving oral antiviral treatment at Screening must continue their treatment regimen until the time of randomization, when it will be discontinued.
- Any previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit.
- Estimated creatinine clearance (CLcr) ≥ 50 mL/min(using the Cockcroft-Gault method)based on serum creatinine and actual body weight as measured at the screening evaluation, as follows:
(140-age in years)(body weight [kg]) (72)(serum creatinine [mg/dL]) 8) Normal ECG (or if abnormal, determined by the Investigator not to be clinically significant).
9) Must be willing and able to comply with all study requirements.
Exclusion Criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
- Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
- Co-infection with HCV virus, HIV, or HDV.
- Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).
- Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage).
Abnormal hematological and biochemical parameters, including:
- Hemoglobin < 10 g/dl
- Absolute neutrophil count < 0.75 × 109/L
- Platelets ≤ 50 × 109/L
- AST or ALT > 10 × ULN
- Total Bilirubin > 2.5 × ULN
- Albumin < 3.0 g/dL
- INR > 1.5 × ULN (unless stable on anticoagulant regimen)
- Received solid organ or bone marrow transplant.
- Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the investigator.
- Significant bone disease (e.g. osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures.
- Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc).
- Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
- Known hypersensitivity to study drugs, metabolites, or formulation excipients.
- Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.
- Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days.
Sites / Locations
- The First Hospital of Jilin University
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
HS-10234 25mg
TDF 300mg
Open-label HS-10234
HS-10234 + TDF placebo for up to 96 weeks
TDF + HS-10234 placebo for up to 96 weeks
All participants who complete the double-blind period (96 weeks) will be eligible to receive open-label HS-10234 until week 144 of the study.