A Study of TAF in Combination With PEG-IFN and Hepalatide in Subjects With Chronic Hepatitis B

Overview

The study is designed to assess efficacy of hepalatide in Combination with Pegylated Interferon and TAF compared to Pegylated Interferon in Combination with TAF in patients with Chronic Hepatitis B .Subjects will be randomly assigned to the hepalatide or placebo groups , 15 subjects in each group . Subjects will receive hepalatide+Pegylated Interferon +TAF treatment for 48 weeks or placebo +Pegylated Interferon +TAF treatment for 48 weeks , followed by a safety follow-up for 24 weeks.

Full Title of Study: “A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center Study of Finite Therapy of TAF in Combination With PEG-IFN and Hepalatide in Subjects With Chronic Hepatitis B”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: December 2023

Detailed Description

Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. Pegylated interferon and TAF are approved drugs for the treatment of chronic HBV infection . The primary hypothesis of this study is that combination regimen of hepalatide+NA+Pegylated interferon is more efficacious than NA+Pegylated interferon treatment , as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4weeks), Treatment Period (48 weeks) and Follow-up (FU) Period (24 weeks). Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 76 weeks (including screening period).

Interventions

  • Drug: hepalatide
    • 4.2 mg, once daily, subcutaneously
  • Drug: Pegylated Interferon
    • 90 μg,once week ,subcutaneously
  • Drug: TAF
    • 25 mg,once daily, ,orally
  • Drug: Placebo
    • 4.2 mg, once daily, subcutaneously

Arms, Groups and Cohorts

  • Experimental: Arm1:hepalatide+Pegylated Interferon+TAF
    • hepalatide 4.2 mg/day subcutaneously (s.c.) +Pegylated Interferon 90 μg/week subcutaneously (s.c.) +TAF 25mg/day treatment for 48 weeks
  • Placebo Comparator: Arm2:placebo+Pegylated Interferon+TAF
    • placebo 4.2 mg/day subcutaneously (s.c.) +Pegylated Interferon 90 μg/week subcutaneously (s.c.)+TAF 25mg/day treatment for 48 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Sustained virologic response
    • Time Frame: week 72
    • Serum HBV DNA <20 IU/mL
  • HBsAg seroclearance
    • Time Frame: week 72
    • Hepatitis B Surface Antigen (HBsAg)<0.05index

Secondary Measures

  • NA recurrence rate
    • Time Frame: week 72
    • Percentage of participants requiring NA re-treatment
  • Virological relapse
    • Time Frame: week 72
    • Central laboratory test HBV DNA >2000IU/ml twice in a month after drug discontinuation
  • Clinical relapse
    • Time Frame: week 72
    • After participants have achieved virologic response and drug discontinuation ,central laboratory test ALT>2×ULN,HBV DNA>2000IU/ml
  • HBsAg reduction from baseline
    • Time Frame: week 72
    • Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels) from baseline
  • HBsAg serologic conversion
    • Time Frame: week 72
    • HBsAg serologic conversion
  • Change in liver elasticity from baseline
    • Time Frame: week 72
    • Change in liver elasticity from baseline

Participating in This Clinical Trial

Inclusion Criteria

  • 1. 18 years ≤ age ≤ 60 years, both sexes. 2. HBsAg (+) or HBV DNA (+) for ≧ 6 months 3. HBeAg(-) 4. on stable treatment for NAs for ≧ 2 years. 5. HBV DNA <LLQD (lower limit of quantitative detection) at screening. 6. ULN<ALT<10×ULN. 7. total serum bilirubin <2×ULN. 8. no childbirth plan within 2 years and agree to take effective contraceptive measures throughout the treatment period and within 3 months after the last dose, and that the woman is not pregnant or breastfeeding. 9. have not participant in another clinical trial within 3 months 10. have good compliance with the study protocol. 11. the subject understands and agrees to sign the informed consent form Exclusion Criteria:

  • 1. contraindications to pegylated interferon therapy, such as major depression, epilepsy, autoimmune disease, uncontrolled thyroid abnormal thyroid function, etc. 2. clinical evidence of cirrhosis: e.g., definite cirrhosis on imaging such as abdominal ultrasound and CT; liver biopsy with Metavir fibrosis score of 4; clinical diagnosis of cirrhosis by the investigator. 3. decompensated liver disease: PT > 1.2 x ULN, serum albumin < 35 g/L 4. liver function Child-Pugh grade B-C or score >6 5. any of the following. 1. history of decompensated liver disease (ascites, hepatic encephalopathy, variceal hemorrhage, hepatorenal syndrome, etc.) 2. history of severe heart disease (including unstable or uncontrolled heart disease within 6 months) 3. uncontrolled epilepsy, severe mental illness or history of severe mental illness 4. history of organ transplantation. 5. diabetes mellitus and hypertension that are not effectively controlled 6. autoimmune diseases, immune-related extrahepatic manifestations (vasculitis, purpura, nodular arteritis, peripheral neuropathy and glomerulonephritis) , thyroid disease, malignancy, and immunosuppressive therapy. 7. with underlying diseases such as malignancy, severe infections, heart failure and chronic obstructive pulmonary disease, and other serious diseases diseases. 8. History of alcohol or drug abuse. 6. creatinine clearance <60mL/min. 7. co-infected with hepatitis A, C, D or E virus, HIV infection. 8. subjects who must be treated with anti-HBV nucleoside (acid) analogs other than TAF during the treatment period. 9. subjects who have used interferon within 6 months prior to the screening 10. subjects with positive anti-HBV Pre-S1 antibody. 11. Abnormal blood tests: white blood cell count < 3×10^9 /L, neutrophil count < 1.5×10^9/L , platelets < 60×10^9 /L . 12. Positive pregnancy test in women. 13. patients who are taking drugs prohibited by the test and cannot be discontinued 14. patients with known allergy to the test drug or the underlying treatment drug 15. other laboratory or ancillary tests are clearly abnormal and unsuitable for participation in the test.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Shanghai HEP Pharmaceatical Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Qing Zhang, Principal Investigator, Shanghai Tong Ren Hospital
  • Overall Contact(s)
    • Fei Cai, 86-21-68412368, caifei_hep@163.com

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