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

Sponsor

Shanghai HEP Pharmaceatical Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05133856

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: hepalatide Drug: Pegylated Interferon Drug: TAF Drug: Placebo	Phase 2

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: hepalatide 4.2 mg, once daily, subcutaneously Other Names: L47 Drug: Pegylated Interferon 90 μg,once week ,subcutaneously Other Names: PegIFN-alpha-2a Drug: TAF 25 mg,once daily, ,orally Other Names: Vemlidy
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	Drug: Pegylated Interferon 90 μg,once week ,subcutaneously Other Names: PegIFN-alpha-2a Drug: TAF 25 mg,once daily, ,orally Other Names: Vemlidy Drug: Placebo 4.2 mg, once daily, subcutaneously

Arm

Intervention/Treatment

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

Drug: hepalatide

4.2 mg, once daily, subcutaneously

Other Names:

L47

Drug: Pegylated Interferon

90 μg,once week ,subcutaneously

Other Names:

PegIFN-alpha-2a

Drug: TAF

25 mg,once daily, ,orally

Other Names:

Vemlidy

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

Drug: Pegylated Interferon

90 μg,once week ,subcutaneously

Other Names:

PegIFN-alpha-2a

Drug: TAF

25 mg,once daily, ,orally

Other Names:

Vemlidy

Drug: Placebo

4.2 mg, once daily, subcutaneously

Outcome Measures

Primary Outcome Measures

Sustained virologic response [week 72]
Serum HBV DNA <20 IU/mL
HBsAg seroclearance [week 72]
Hepatitis B Surface Antigen (HBsAg)<0.05index

Secondary Outcome Measures

NA recurrence rate [week 72]
Percentage of participants requiring NA re-treatment
Virological relapse [week 72]
Central laboratory test HBV DNA >2000IU/ml twice in a month after drug discontinuation
Clinical relapse [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 [week 72]
Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels) from baseline
HBsAg serologic conversion [week 72]
HBsAg serologic conversion
Change in liver elasticity from baseline [week 72]
Change in liver elasticity from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. 18 years ≤ age ≤ 60 years, both sexes.

HBsAg (+) or HBV DNA (+) for ≧ 6 months
HBeAg(-)
on stable treatment for NAs for ≧ 2 years.
HBV DNA <LLQD (lower limit of quantitative detection) at screening.
ULN<ALT<10×ULN.
total serum bilirubin <2×ULN.
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.
have not participant in another clinical trial within 3 months
have good compliance with the study protocol.
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.

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