Clinical trial NCT04426968: A Phase II Study of Hepalatide in Subjects With Chronic Hepatitis B
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Shanghai HEP Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-11
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: virological response
timeFrame: 24weeks
Secondary outcomes:
measure: HBV DNA down from baseline
timeFrame: 24weeks
Other outcomes:
measure: Virological suppression
timeFrame: 24weeks
measure: No response
timeFrame: 24weeks
measure: Partial virological response
timeFrame: 24weeks
measure: HBsAg is down from baseline
timeFrame: 24weeks
measure: HBeAg turned negative
timeFrame: 24weeks
measure: HBeAg is down from baseline
timeFrame: 24weeks
measure: ALT recurrence
timeFrame: 24weeks
measure: Histological response
timeFrame: 24weeks
Locations:
city: Beijing
country: China
facility: The fifth medical center of PLA
state: Beijing
city: Changchun
country: China
facility: Jilin Hepatobiliary Disease Hospital
city: Changchun
country: China
facility: The first hospital of Jilin University
city: Chizhou
country: China
facility: Chizhou People's Hospital
city: Chongqing
country: China
facility: The First Hospital Affiliated to the Army Medical University
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhenzhou
country: China
facility: Henan Provincial Infectious Disease Hospital
Study officials:
affiliation: The fifth medical center of PLA
name: Fusheng Wang
role: PRINCIPAL_INVESTIGATOR
References: