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

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

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 Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Hepalatide 2.1mg; Drug: Pegylated Interferon; Drug: Hepalatide 4.2mg; Drug: Hepalatide 6.3mg; Drug: placebo 2.1mg; Drug: placebo 4.2mg; Drug: placebo 6.3mg

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 Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaolu Tang; Phone Number: 619 86-21-68412368; Email: tangxiaolu@heppharma.com
• Study Contact Backup: Name: Xian Gao; Phone Number: 620 86-21-68412368; Email: gaoxian@heppharma.com

Study Locations

• China
  • Changchun, China
    • The First Hospital of Jilin University
  • Changchun, China
    • Jilin Hepatobiliary Disease Hospital
  • Chizhou, China
    • Chizhou People's Hospital
  • Chongqing, China
    • The First Hospital Affiliated to the Army Medical University
  • Nanchang, China
    • The First Affiliated Hospital Of NanChang University
  • Nanjing, China
    • The Second Hospital of Nanjing
  • Qingyuan, China
    • Qingyuan People's Hospital
  • Shanghai, China
    • Shanghai Tongren Hospital
  • Shenyang, China
    • The Sixth People's Hospital of Shenyang
  • Zhengzhou, China
    • HeNan Provincial People's Hospital
  • Zhenzhou, China
    • Henan Provincial Infectious Disease Hospital
  • Beijing
    • Beijing, Beijing, China, 100039
      • The fifth medical center of PLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Hepalatide 2.1mg; 2.1 mg/day subcutaneously (s.c.) for 24 week; Other Names: L47; Drug: Pegylated Interferon; 180 ug/week subcutaneously (s.c.) for 28 week; Other Names: Pegasys
Experimental: 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	Drug: Pegylated Interferon; 180 ug/week subcutaneously (s.c.) for 28 week; Other Names: Pegasys; Drug: Hepalatide 4.2mg; 4.2mg/day subcutaneously (s.c.) for 24 week; Other Names: L47
Experimental: 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	Drug: Pegylated Interferon; 180 ug/week subcutaneously (s.c.) for 28 week; Other Names: Pegasys; Drug: Hepalatide 6.3mg; 6.3mg/day subcutaneously (s.c.) for 24 week; Other Names: L47
Active Comparator: 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	Drug: Pegylated Interferon; 180 ug/week subcutaneously (s.c.) for 28 week; Other Names: Pegasys; Drug: placebo 2.1mg; 2.1 mg/day subcutaneously (s.c.) for 24 week; Drug: placebo 4.2mg; 4.2 mg/day subcutaneously (s.c.) for 24 week; Drug: placebo 6.3mg; 6.3 mg/day subcutaneously (s.c.) for 24 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
initial virological response	HBV DNA<20 IU/ml	24weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBV DNA down from baseline	HBV DNA down from baseline log10	24weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological suppression	HBV DNA <2,000 IU/ml	24weeks
No response	HBsAg >20,000 IU/ml and HBV DNA lower than baseline <2log10 IU/ml	24weeks
Partial virological response	HBV DNA >20 IU/ml and ≥2log10 IU/ml lower than baseline	24weeks
HBsAg is down from baseline	HBsAg is down from baseline log10	24weeks
HBeAg turned negative	HBeAg <0.05 index	24weeks
HBeAg is down from baseline	HBeAg is down from baseline log10	24weeks
ALT recurrence	ALT≤1.25×ULN	24weeks
Histological response	Liver tissue inflammatory necrosis score reduced by ≥2 points with no increased liver fibrosis score; liver fibrosis score reduced by ≥1 point	24weeks

Collaborators and Investigators

• Sponsor: Shanghai HEP Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Fusheng Wang, The fifth medical center of PLA

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons
• Other Study ID Numbers: L47-HB-II-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No