A Study of Hepalatide Combined With TAF and PEG-IFN as Finite Treatment of Chronic Hepatitis B Patients

A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients

The study is designed to assess efficacy of a finitie treatment in Chronic Hepatitis B patients who had stable treatment of NAs for ≧ 2 years， which is compared hepalatide in combination with Pegylated Interferon + TAF with Pegylated Interferon +TAF. 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 +PegylatedInterferon +TAF treatment for 48 weeks , Then, stopping hepalatide and Pegylate Interferon treatments and followed with further 8 weeks follow-up.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Tenofovir Alafenamide Tablets; Drug: Pegylated Interferon alfa 2a; Drug: Placebo of Hepalatide; Drug: Hepalatide

Detailed Description

Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. The aim of this study is to assess efficacy of a finitie treantment , that combination regimen of hepalatide+half dose Pegylated interferon + TAF , 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 (8 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 60 weeks (including screening period).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200050
      • Shanghai Tong Ren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. HBsAg or/and HBV DNA Positive for at least 6 months

  2. HBeAg negative

  3. Received NAs stabilization therapy for at least 2 years

  4. ALT≤ 2×ULN

  5. HBV DNA< LLQD(lower limit of quantitative detection) in Screening

  6. Serum total bilirubin<2×ULN

  7. 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.

  8. have not participant in another clinical trial within 3 months before screening

  9. Subjects have good compliance with the protocol

  10. Subjects understood and agreed to sign the informed consent form.

Exclusion Criteria:

• 1. Contraindications of Peginterferon such as depressive disorder, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction, etc

  2. Subjects with cirrhosis, e.g., definite cirrhosis on imaging such as abdominal ultrasound and CT; liver biopsy with Metavir fibrosis score = 4; clinical diagnosis of cirrhosis by the investigator.

  3. Decompensated liver disease

  4. Child-Pugh score of B-C or over 6 points.

  5. Subjects with any of the following circumstances

• History of decompensated liver disease
• History of serious heart disease (including unstable or uncontrolled heart disease within 6 months)
• Uncontrolled seizures, severe psychiatric disorders, or a history of psychiatric disorders
• with history of organ transplantation
• with poorly controlled diabetes and hypertension
• with autoimmune diseases, immune-related extrahepatic manifestations, thyroid disease, malignant tumors, or in immunosuppressive therapy
• underlying diseases such as malignant tumor, severe infection, heart failure and chronic obstructive pulmonary disease and other serious diseases.

• with history of alcohol or drug abuse

  6. Creatinine clearance <60 mL/min.

  7. HAV, HCV, HDV, HEV or HIV co-infection

  8. Subjects who must be treated with Nucleosides (acids) other than TAF during treatment period

  9. Subjects who used interferon in the 6 months prior to the screening period

  10. Positive for anti-HBV Pre-S1 antibody.

  11. Hemocytopenia: White blood cells < 3 × 10^9 / L, neutrophil < 1.5 × 10^9 / L, platelet < 60 × 10^9 / L,

  12. Female subjects pregnancy test positive

  13. known to be allergic to the investigational drug or the underlying treatment drug

  14. 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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo+ TAF + PEG-IFN; Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.	Drug: Tenofovir Alafenamide Tablets; 25mg, p.o., qd for 48 weeks; Other Names: Vemlidy; Drug: Pegylated Interferon alfa 2a; 90ug, s.c., qw for 48 weeks; Other Names: Pegasys; Drug: Placebo of Hepalatide; s.c., qd for 48 weeks; Other Names: Placebo
Experimental: Hepalatide + TAF + PEG-IFN; Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.	Drug: Tenofovir Alafenamide Tablets; 25mg, p.o., qd for 48 weeks; Other Names: Vemlidy; Drug: Pegylated Interferon alfa 2a; 90ug, s.c., qw for 48 weeks; Other Names: Pegasys; Drug: Hepalatide; 6.3mg, s.c., qd for 48 weeks; Other Names: L47

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with negative conversion of HBsAg	Proportion of subjects with negative conversion of HBsAg treatment at 8 weeks off treatment	56 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with virological relapse(VR) at 8 weeks off treatment	VR: reappearance of HBV DNA > 2000 IU/ml from undetectable status	56 Weeks
Number of subjects with clinical relapse(CR) at 8 weeks off treatment	CR: the presence of VR with the elevation of alanine transaminase (ALT) more than two times upper limit of normal (ULN)	56 Weeks
HBsAg is down from baseline at 8 weeks off treatment	HBsAg is down from baseline log10	56 Weeks
Number of subjects with Serological conversion of HBsAg	Number of subjects with Serological conversion of HBsAg at 8 weeks off treatment	56 Weeks
Change in liver stiffness at 8 weeks off treatment	The findings of Liver stiffness measurement(LSM) of Fibroscan/FibroTouch at week 8 off treatment compared to baseline	56 Weeks

Collaborators and Investigators

• Sponsor: Shanghai HEP Pharmaceutical Co., Ltd.
• Collaborators: Shanghai Tong Ren Hospital; Shanghai East Hospital
• Investigators: Principal Investigator: Qin Zhang, Shanghai Tong Ren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2022
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: hepalatide, Hepatitis B，finite treatment,
• 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; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Immunologic Factors; Tenofovir; Interferons; Interferon-alpha; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: L47-HB-FIN-1(New Finite)

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