A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined With Pegylated Interferon in Subjects With Chronic Hepatitis B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 12
- 主要终点
- virological response
研究概览
简要总结
A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined with Pegylated Interferon in Subjects with Chronic Hepatitis B
详细描述
The study is a 4-arm parallel design, randomized, double-blind, placebo-controlled, multicenter, dose-effect relationship, phase II clinical trial. The study is designed to assess efficacy and safety of 3 Doses of hepalatide in Combination with Pegylated Interferon Compared to Pegylated Interferon Alone in patients with Chronic Hepatitis B .Subjects will be randomly assigned to the 2.1mg, 4.2mg, and 6.3mg dose groups , 32 subjects in each group . The subjects in each dose group will be randomly and double-blindly administered the corresponding dose of trial drug or placebo in a ratio of 3:1. The subjects in each dose group who received placebo treatment combine as the placebo group. All subjects will receive Pegylated Interferon treatment for 28 weeks as the basic treatment,trial drug or placebo treatment for 24 weeks continuously , followed by a safety follow-up for 4 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age from 18 to 60 years inclusively at the time of signing Informed Consent Form.
- •HBsAg or/and HBV DNA Positive for at least 6 months before Screening.
- •Subjects did not receive interferon treatment and did not receive nucleotide/nucleoside analogue within 6 months
- •HBeAg positive or negative
- •HBV DNA≥20,000 IU/ml (HBeAg positive) or HBV DNA≥2,000 IU/ml (HBeAg negative)
- •2×ULN ≤ALT≤10×ULN
- •Serum total bilirubin<2×ULN
- •Subjects had no history of decompensated liver disease（Ascites, jaundice, hepatic encephalopathy, varicose hemorrhage）, serious heart disease (including unstable or uncontrolled heart disease within 6 months),serious mental illness (especially depression),organ transplantation .subjects have no uncontrolled epilepsy, mental illness, diabetes and hypertension,no autoimmune disease, immune related extrahepatic manifestations (vasculitis, purpura, nodular arteritis, peripheral neuropathy and glomerulonephritis), thyroid disease, malignant tumor, immunosuppressive therapy; no basic diseases and other serious diseases such as serious infection, retinal disease, heart failure and chronic obstructive pulmonary disease; no alcohol and drug abuse.
- •Subjects must agree to use a highly effective contraception for 2 years , female subjects are not pregnant or breastfeeding
- •Subjects did not donate blood or as clinical trial subjects 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
- •Decompensated liver disease: direct bilirubin > 1.2 × ULN,
- •Prothrombin time > 1.2 × ULN, serum albumin < 35 g / L
- •Severe liver fibrosis or cirrhosis: METAVIR score of liver biopsy is 4 points; or or Child-Pugh score> 7
- •Hemocytopenia: neutrophil < 1 × 10^9 / L, platelet < 50 × 10^9 / L, hemoglobin < 100g / L (female) or hemoglobin < 110g / L (male) points
- •HAV,HCV,HDV,HEV or HIV infection
- •Pegylated interferon therapy is contraindicated
- •Allergic to interferon, Such as severe depression, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction and so on
- •severe retinopathy or eye disease(Eye diseases due to high blood pressure or diabetes, CMV retinitis, macular degeneration)
- •Positive for anti-HBV Pre-S1 antibody.
- •Hamilton Depression Scale (HAMD, 17 items) score > 17 points
- •Female subjects pregnancy test positive
- •Other laboratories or auxiliary examinations are obviously abnormal
研究组 & 干预措施
Hepalatide 2.1mg+Pegylated Interferon
Hepalatide 2.1mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Hepalatide 2.1mg (Drug)
Hepalatide 2.1mg+Pegylated Interferon
Hepalatide 2.1mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Pegylated Interferon (Drug)
Hepalatide 4.2mg+Pegylated Interferon
Hepalatide 4.2mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Hepalatide 4.2mg (Drug)
Hepalatide 4.2mg+Pegylated Interferon
Hepalatide 4.2mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Pegylated Interferon (Drug)
Hepalatide 6.3mg+Pegylated Interferon
Hepalatide 6.3mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Hepalatide 6.3mg (Drug)
Hepalatide 6.3mg+Pegylated Interferon
Hepalatide 6.3mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Pegylated Interferon (Drug)
placebo+Pegylated Interferon
Hepalatide placebo s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: placebo 2.1mg (Drug)
placebo+Pegylated Interferon
Hepalatide placebo s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: placebo 4.2mg (Drug)
placebo+Pegylated Interferon
Hepalatide placebo s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: placebo 6.3mg (Drug)
placebo+Pegylated Interferon
Hepalatide placebo s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks.
PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks
干预措施: Pegylated Interferon (Drug)
结局指标
主要结局
virological response
时间窗: 24weeks
次要结局
- HBV DNA down from baseline(24weeks)