Hepatitis B, Chronic
Conditions
Brief summary
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
Detailed description
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.
Interventions
DRUGHepalatide 2.1mg
2.1 mg/day subcutaneously (s.c.) for 24 week
DRUGHepalatide 4.2mg
4.2mg/day subcutaneously (s.c.) for 24 week
DRUGHepalatide 6.3mg
6.3mg/day subcutaneously (s.c.) for 24 week
DRUGplacebo 2.1mg
2.1 mg/day subcutaneously (s.c.) for 24 week
DRUGplacebo 4.2mg
4.2 mg/day subcutaneously (s.c.) for 24 week
DRUGplacebo 6.3mg
6.3 mg/day subcutaneously (s.c.) for 24 week
DRUGPegylated Interferon
180 ug/week subcutaneously (s.c.) for 28 week
Sponsors
Shanghai HEP Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age from 18 to 60 years inclusively at the time of signing Informed Consent Form. 2. HBsAg or/and HBV DNA Positive for at least 6 months before Screening. 3. Subjects did not receive interferon treatment and did not receive nucleotide/nucleoside analogue within 6 months 4. HBeAg positive or negative 5. HBV DNA≥20,000 IU/ml (HBeAg positive) or HBV DNA≥2,000 IU/ml (HBeAg negative) 6. 2×ULN ≤ALT≤10×ULN 7. Serum total bilirubin\<2×ULN 8. 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. 9. Subjects must agree to use a highly effective contraception for 2 years , female subjects are not pregnant or breastfeeding 10. Subjects did not donate blood or as clinical trial subjects within 3 months before screening 11. Subjects have good compliance with the protocol 12. Subjects understood and agreed to sign the informed consent form.
Exclusion criteria
1. Decompensated liver disease: direct bilirubin \> 1.2 × ULN, 2. Prothrombin time \> 1.2 × ULN, serum albumin \< 35 g / L 3. Severe liver fibrosis or cirrhosis: METAVIR score of liver biopsy is 4 points; or or Child-Pugh score\> 7 4. Hemocytopenia: neutrophil \< 1 × 10\^9 / L, platelet \< 50 × 10\^9 / L, hemoglobin \< 100g / L (female) or hemoglobin \< 110g / L (male) points 5. HAV,HCV,HDV,HEV or HIV infection 6. Pegylated interferon therapy is contraindicated 7. Allergic to interferon, Such as severe depression, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction and so on 8. severe retinopathy or eye disease(Eye diseases due to high blood pressure or diabetes, CMV retinitis, macular degeneration) 9. Positive for anti-HBV Pre-S1 antibody. 10. Hamilton Depression Scale (HAMD, 17 items) score \> 17 points 11. Female subjects pregnancy test positive 12. Other laboratories or auxiliary examinations are obviously abnormal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| virological response | 24weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HBV DNA down from baseline | 24weeks | HBV DNA down from baseline log10 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Partial virological response | 24weeks | HBV DNA \>20 IU/ml and ≥2log10 IU/ml lower than baseline |
| HBsAg is down from baseline | 24weeks | HBsAg is down from baseline log10 |
| HBeAg turned negative | 24weeks | HBeAg \<0.05 index |
| Virological suppression | 24weeks | HBV DNA \<2,000 IU/ml |
| ALT recurrence | 24weeks | ALT≤1.25×ULN |
| Histological response | 24weeks | Liver tissue inflammatory necrosis score reduced by ≥2 points with no increased liver fibrosis score; liver fibrosis score reduced by ≥1 point |
| HBeAg is down from baseline | 24weeks | HBeAg is down from baseline log10 |
| No response | 24weeks | HBsAg \>20,000 IU/ml and HBV DNA lower than baseline \<2log10 IU/ml |
Countries
China
Outcome results
None listed