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

Phase 2

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Hepalatide; Drug: Placebo of Hepalatide; Drug: Tenofovir Alafenamide Tablets; Drug: Pegylated Interferon alfa 2a

• Registration Number: NCT05244057
• Lead Sponsor: Shanghai HEP Pharmaceutical Co., Ltd.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-02-03
• Study First Submitted QC: 2022-02-16
• Study First Posted: 2022-02-17
• Study Start: 2022-08-23
• Status Verified: 2023-12
• Primary Completion: 2024-06-24
• Study Completion: 2024-06-24
• Last Update Submitted: 2024-07-11
• Last Update Posted: 2024-07-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo+ TAF + PEG-IFN	Pegylated Interferon alfa 2a	Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
Hepalatide + TAF + PEG-IFN	Hepalatide	Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
Placebo+ TAF + PEG-IFN	Placebo of Hepalatide	Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
Hepalatide + TAF + PEG-IFN	Tenofovir Alafenamide Tablets	Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
Hepalatide + TAF + PEG-IFN	Pegylated Interferon alfa 2a	Patients will receive 6.3mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.
Placebo+ TAF + PEG-IFN	Tenofovir Alafenamide Tablets	Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with negative conversion of HBsAg	56 Weeks	Proportion of subjects with negative conversion of HBsAg treatment at 8 weeks off treatment

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Shanghai Tong Ren Hospital; 🇨🇳 Shanghai, Shanghai, China