A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Proportion of subjects with negative conversion of HBsAg
研究概览
简要总结
The study is designed to assess efficacy of a finitie treatment in Chronic Hepatitis B patients who had stable treatment of NAs for ≧ 2 years， which is compared hepalatide in combination with Pegylated Interferon + TAF with Pegylated Interferon +TAF. Subjects will be randomly assigned to the hepalatide or placebo groups , 15 subjects in each group . Subjects will receive hepalatide+Pegylated Interferon +TAF treatment for 48 weeks or placebo +PegylatedInterferon +TAF treatment for 48 weeks , Then, stopping hepalatide and Pegylate Interferon treatments and followed with further 8 weeks follow-up.
详细描述
Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. The aim of this study is to assess efficacy of a finitie treantment , that combination regimen of hepalatide+half dose Pegylated interferon + TAF , as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4weeks), Treatment Period (48 weeks) and Follow-up (FU) Period (8 weeks). Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 60 weeks (including screening period).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HBsAg or/and HBV DNA Positive for at least 6 months
- •HBeAg negative
- •Received NAs stabilization therapy for at least 2 years
- •HBV DNA< LLQD(lower limit of quantitative detection) in Screening
- •Serum total bilirubin<2×ULN
- •no childbirth plan within 2 years and agree to take effective contraceptive measures throughout the treatment period and within 3 months after the last dose, and that the woman is not pregnant or breastfeeding.
- •have not participant in another clinical trial within 3 months before screening
- •Subjects have good compliance with the protocol
- •Subjects understood and agreed to sign the informed consent form.
排除标准
- •Contraindications of Peginterferon such as depressive disorder, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction, etc
- •Subjects with cirrhosis, e.g., definite cirrhosis on imaging such as abdominal ultrasound and CT; liver biopsy with Metavir fibrosis score = 4; clinical diagnosis of cirrhosis by the investigator.
- •Decompensated liver disease
- •Child-Pugh score of B-C or over 6 points.
- •Subjects with any of the following circumstances
- •History of decompensated liver disease
- •History of serious heart disease (including unstable or uncontrolled heart disease within 6 months)
- •Uncontrolled seizures, severe psychiatric disorders, or a history of psychiatric disorders
- •with history of organ transplantation
- •with poorly controlled diabetes and hypertension
- •with autoimmune diseases, immune-related extrahepatic manifestations, thyroid disease, malignant tumors, or in immunosuppressive therapy
- •underlying diseases such as malignant tumor, severe infection, heart failure and chronic obstructive pulmonary disease and other serious diseases.
- •with history of alcohol or drug abuse
- •Creatinine clearance <60 mL/min.
- •HAV, HCV, HDV, HEV or HIV co-infection
- •Subjects who must be treated with Nucleosides (acids) other than TAF during treatment period
- •Subjects who used interferon in the 6 months prior to the screening period
- •Positive for anti-HBV Pre-S1 antibody.
- •Hemocytopenia: White blood cells < 3 × 10^9 / L, neutrophil < 1.5 × 10^9 / L, platelet < 60 × 10^9 / L,
- •Female subjects pregnancy test positive
- •known to be allergic to the investigational drug or the underlying treatment drug
- •Other laboratories or auxiliary examinations are obviously abnormal
研究组 & 干预措施
Hepalatide + TAF + PEG-IFN
Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Hepalatide (Drug)
Hepalatide + TAF + PEG-IFN
Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Tenofovir Alafenamide Tablets (Drug)
Hepalatide + TAF + PEG-IFN
Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Pegylated Interferon alfa 2a (Drug)
Placebo+ TAF + PEG-IFN
Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Placebo of Hepalatide (Drug)
Placebo+ TAF + PEG-IFN
Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Tenofovir Alafenamide Tablets (Drug)
Placebo+ TAF + PEG-IFN
Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
干预措施: Pegylated Interferon alfa 2a (Drug)
结局指标
主要结局
Proportion of subjects with negative conversion of HBsAg
时间窗: 56 Weeks
Proportion of subjects with negative conversion of HBsAg treatment at 8 weeks off treatment
次要结局
- Change in liver stiffness at 8 weeks off treatment(56 Weeks)
- Number of subjects with virological relapse(VR) at 8 weeks off treatment(56 Weeks)
- HBsAg is down from baseline at 8 weeks off treatment(56 Weeks)
- Number of subjects with Serological conversion of HBsAg(56 Weeks)
- Number of subjects with clinical relapse(CR) at 8 weeks off treatment(56 Weeks)