Functional Cure Rate of Peg-IFNα-2b Combined With TAF in HBeAg Negative CHB Patients

Peginterferon Alfa-2b Combined With Tenofovir Alafenamide Improves the Functional Cure Rate in Patients With HBeAg Negative Chronic Hepatitis B: an Open-labeled, Multicenter, Randomized and Controlled Clinical Study

The study is aimed to explore the safety and efficacy of the pulse usage , comparing to continuous usage, of Peginterferon alfa-2b Injection (PEG IFN α-2b) Combined With tenofovir alafenamide (TAF) in treatment of naive chronic hepatitis B patients with HBeAg negative.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: PEG IFN α-2b; TAF; Biological: PEG IFN α-2b; TAF

Detailed Description

Using antiviral drugs with different mechanisms of action is one of the effective means to improve the therapeutic outcome at present. At the same time, PEG-IFN is currently recognized as the only drug that can improve the functional cure rate of chronic hepatitis B, and PEG-IFN clinical application is limited due to adverse reactions. Exploring ways to reduce adverse reactions of PEG-IFN and improve PEG-IFN curative effects is the hot spot topic but also difficult at present.

Previously clinical practice have found that the temporary withdrawal of interferon have little influences on the whole clinical outcome in patients withdrawal of interferon due to adverse reactions, and there is indeed a continuous effect after the withdrawal of PEG-IFN for a certain period of time. Therefore, it is conceive that pulse usage of PEG-IFN (eg. use for 8 weeks followed by 4 weeks off) may be a effective method to reduce PEG-IFN adverse reactions while ensuring efficacy.

By comparing the safety and efficacy of pulsed and continuous combination therapy of Peg-IFNα-2b with TAF and in treatment naive HBeAg-negative CHB patients, the investigators hope to develop a better treatment plan for chronic hepatitis B.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Aged between 18 and 65,included.
• HBsAg positive, HBeAg negative, anti HBE antibody positive, HBV-DNA ≥ 2x10^3 IU/ml, ALT is continuously or repeatedly abnormal, or there is definite inflammation, necrosis and / or fibrosis (≥ G2/S2) confirmed in liver biopsy.
• Received no antiviral treatment previously.
• pregnancy test of Female subjects of childbearing must be negative before the enrollment, and all potential subjects must agree to take effective contraceptive measures during the treatment period and within half a year after the end of the treatment.
• Understand and sign the informed consent voluntarily.

Exclusion criteria:

• Known allergy to interferon, nucleos(t)ide drugs, or any ingredient of the drug.
• Currently co-infection with HAV, HCV, HDV, HEV, HIV, or any other virus.
• Cirrhosis or Child-Pugh score of 7 or above.
• Liver disease caused by other reasons (eg. autoimmune liver disease, alcoholic liver disease, nonalcoholic fatty liver disease, drug-induced hepatitis, hepatolenticular degeneration, etc.).
• Pregnant or lactating women.
• Alcoholism or drug abuse within one year prior to the screening.
• Neutrophil count<1.5×10^9/L, hemoglobin<100g/L, or platelet count<80×10^9/L.
• Serum creatinine was higher than the upper limit of normal at screening.
• History of serious disease in heart, brain, kidney, retina, muscle, or other major organ and systems.
• Have a history of mental illness or family history of mental illness, or Hamilton Depression Scale score ≥ 7 points.
• Have a history of endocrine system or autoimmune diseases, such as thyroid disease, systemic lupus erythematosus, sarcoidosis, autoimmune thrombocytopenic purpura, psoriasis, etc.
• Chronic diseases requiring long-term treatment, such as uncontrolled hypertension, diabetes, chronic obstructive pulmonary disease, etc.
• Malignant tumor.
• Suspected hepatocellular carcinoma in B-ultrasound at screening; or fetoprotein alpha was greater than 100ng/ml, or cannot remain stable within 3 months before screening.
• Accepted organ transplantation previously.
• Other reasons that the investigator considers unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: continuous treatment arm	Biological: PEG IFN α-2b; TAF; TAF was orally administered once a day, and PEG IFN α-2b was subcutaneously injected 135 μg or 180μg once a week. treatment continuous for 48 weeks.; Biological: PEG IFN α-2b; TAF; TAF was orally administered once a day, and PEG IFN α-2b was subcutaneously injected 135 μg or 180μg once a week for 8 weeks and followed by 4 weeks off. treatment continuous for 48 weeks.
Experimental: pulse treatment arm	Biological: PEG IFN α-2b; TAF; TAF was orally administered once a day, and PEG IFN α-2b was subcutaneously injected 135 μg or 180μg once a week. treatment continuous for 48 weeks.; Biological: PEG IFN α-2b; TAF; TAF was orally administered once a day, and PEG IFN α-2b was subcutaneously injected 135 μg or 180μg once a week for 8 weeks and followed by 4 weeks off. treatment continuous for 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The rate of HBsAg negative	week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
change in HBsAg level from baseline	week 48
The Rate of HBsAg seroconversion	week 48
Proportion of patients with HBV DNA Below the detection limit	week 24 and week 48
Number of patients with treatment-related adverse events	from baseline to week 48

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Chronic hepatitis B; Peg-IFN; Functional cure rate
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferon-alpha; Interferon alpha-2; Interferon-alfa-1b
• Other Study ID Numbers: KY2022-517

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No