A Phase II Study of Hepalatide in Subjects With Chronic Hepatitis B

Phase 2

Completed

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Hepalatide 4.2mg; Drug: Hepalatide 2.1mg; Drug: Hepalatide 6.3mg; Drug: placebo 2.1mg; Drug: Pegylated Interferon; Drug: placebo 4.2mg; Drug: placebo 6.3mg

• Registration Number: NCT04426968
• Lead Sponsor: Shanghai HEP Pharmaceutical Co., Ltd.

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.

Study Timeline

• Study First Submitted: 2020-06-09
• Study First Submitted QC: 2020-06-09
• Study First Posted: 2020-06-11
• Study Start: 2021-06-18
• Status Verified: 2022-12
• Primary Completion: 2023-11-01
• Study Completion: 2023-11-29
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hepalatide 4.2mg+Pegylated Interferon	Hepalatide 4.2mg	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
Hepalatide 6.3mg+Pegylated Interferon	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
Hepalatide 2.1mg+Pegylated Interferon	Hepalatide 2.1mg	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
Hepalatide 6.3mg+Pegylated Interferon	Hepalatide 6.3mg	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
Hepalatide 2.1mg+Pegylated Interferon	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
Hepalatide 4.2mg+Pegylated Interferon	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
placebo+Pegylated Interferon	placebo 2.1mg	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
placebo+Pegylated Interferon	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
placebo+Pegylated Interferon	placebo 4.2mg	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
placebo+Pegylated Interferon	placebo 6.3mg	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

Primary Outcome Measures

Name	Time	Method
virological response	24weeks

Secondary Outcome Measures

Name	Time	Method
HBV DNA down from baseline	24weeks	HBV DNA down from baseline log10

Trial Locations

Locations (12)

Jilin Hepatobiliary Disease Hospital; 🇨🇳 Changchun, China

Shanghai Tongren Hospital; 🇨🇳 Shanghai, China

Chizhou People's Hospital; 🇨🇳 Chizhou, China

The fifth medical center of PLA; 🇨🇳 Beijing, Beijing, China

The first hospital of Jilin University; 🇨🇳 Changchun, China

The First Hospital Affiliated to the Army Medical University; 🇨🇳 Chongqing, China

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, China

Qingyuan People's Hospital; 🇨🇳 Qingyuan, China

The Sixth People's Hospital of Shenyang; 🇨🇳 Shenyang, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, China

Henan Provincial Infectious Disease Hospital; 🇨🇳 Zhenzhou, China

The Second Hospital of Nanjing; 🇨🇳 Nanjing, China