A Phase 3, Randomized, Multicenter, Double-blind, Double-dummy, Parallel-controlled Study to Evaluate the Safety and Efficacy of HS-10234 25 mg QD Versus TDF 300 mg QD for the Treatment of Patients With HBeAg+/- Chronic HBV Infection.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 963
- 试验地点
- 1
- 主要终点
- Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL
研究概览
简要总结
The primary objective of this study is to compare the safety and efficacy of HS-10234 versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with chronic hepatitis B virus (HBV) infection.
详细描述
This is a phase 3, randomized, multicenter, double-blind, double-dummy, parallel-controlled, non-inferiority trial to evaluate the safety and efficacy of HS-10234 25 mg qd versus TDF 300 mg qd. Patients with chronic HBV infection who are positive or negative for the hepatitis B e antigen (HBeAg) will be randomly assigned (2:1) to receive either 25 mg HS-10234 or 300 mg TDF with matching placebo. Randomization will be done by a computer-generated allocation sequence stratified by plasma HBV DNA concentration (HBV DNA< 8 log10IU/mL；HBV DNA ≥8 log10IU/mL) and previous treatment experience (treatment-naive and treatment-experienced). All patients will receive 144 weeks of antiviral therapy. After 96 weeks of double-blind treatment, all subjects will be eligible to receive open-label HS-10234 until 144 weeks.
The primary efficacy endpoint is the proportion of patients with HBV DNA less than 20 IU/mL at week 48 in all patients who are randomly assigned and received at least one dose of study drug using a missing-equals-failed approach. Key pre-specified safety endpoints are bone and renal parameters at week 48. Other pre-specified endpoints include viral suppression, serologic response, normalization of alanine aminotransferase (ALT) levels and the emergence of resistance mutations at week 48, 96 and 144.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •Must be willing and able to comply with all study requirements.
排除标准
- •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.
研究组 & 干预措施
HS-10234 25mg
HS-10234 + TDF placebo for up to 96 weeks
干预措施: HS-10234 (Drug)
HS-10234 25mg
HS-10234 + TDF placebo for up to 96 weeks
干预措施: TDF (Drug)
TDF 300mg
TDF + HS-10234 placebo for up to 96 weeks
干预措施: HS-10234 (Drug)
TDF 300mg
TDF + HS-10234 placebo for up to 96 weeks
干预措施: TDF (Drug)
Open-label HS-10234
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.
干预措施: HS-10234 (Drug)
结局指标
主要结局
Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL
时间窗: Week 48
The primary efficacy endpoint was the proportion of patients with HBV DNA \< 20 IU/mL at week 48 in all patients who are randomly assigned and received HS-10234 25 mg or TDF 300 mg. The safety and tolerance were also observed in two treatment groups.
次要结局
- Evaluation the change from Baseline in Serum Creatinine(Week 48)
- Evaluation the percent Change from Baseline in Spine BMD(Week 48)
- Evaluation the percent Change from Baseline in Hip BMD(Week 48)