IFNA2/ISGs: To Optimize the Therapeutic Pathway of Peginterferon Treatment in Patients With CHB Based on IFNA2p.Ala120Thr /ISGs.

Sponsor

Sun Yat-sen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03771677

Collaborator

First People's Hospital of Foshan (Other)

160

Enrollment

Location

Arms

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is to optimize the clinical therapeutic pathway of peginterferon alfa-2a treatment in patients with chronic hepatitis B based on the detection of interferon gene mutation (IFNA2p.Ala120Thr) and interferon-stimulated genes (ISGs) detection gene spectrum.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Drug: Nucleotide Analog Drug: Interferon Alfa-2A	N/A

Detailed Description

It is estimated that more than 400 million people are infected with hepatitis B virus (HBV) globally.How to make more patients with chronic hepatitis B get clinical treatment through the existing anti-viral treatment is an urgent problem to be solved.This study is a random, multi-center and open experiment,the collaborators includes the second people's hospital of zhongshan city, the eighth people's hospital of guangzhou city, and the first people's hospital of foshan city.

Patients with chronic hepatitis B who were treated with NAs for over 1 year,HBsAg quantification≤1500 IU/mL, HBeAg negative and serum HBV DNA quantification <100 IU/mL were enrolled in this study. In our study, the enrolled patient's IFNA2p.Ala120Thr without variation and ISGs>0.05 were divided into two groups. After randomized grouping and giving informed consent,in one group, patients continued NAs for another 48 weeks. In another group , patients switched to peg-interferon-2a monotherapy for 48 weeks.Patient's BMI, genotype, family history, smoking history, drinking history, other medical history, suspected transmission channels, types and time of use were recorded in this study.Moreover, Patients were assessed every 12 weeks,included liver and kidney function, blood routine, HBV cccDNA, HBeAg quantification, HBsAg quantification, pgRNA and so on.In addition,liver imaging examination and liver hardness test were assessed every six months.

In this study, the "accurate" and "individualized" selection of the long-term interferon anti-hbv treatment will be conducted. Before the treatment, "optimal patients" and "optimal treatment" are selected, in an attempt to improve the response rate and efficacy of interferon,which can improve the cure rate of hepatitis b,proceeding "Individualized" anti-hbv treatment more scientifically and precisely.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Drug: nucleotide analogues(NAs) Drug: Peginterferon alfa-2aDrug: nucleotide analogues(NAs) Drug: Peginterferon alfa-2a

Masking:

None (Open Label)

Masking Description:

Active Comparator:nucleotide analogues(NAs) patients continue to use NAs Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a

Primary Purpose:

Treatment

Official Title:

A Multicenter Clinical Study to Optimize the Therapeutic Pathway of Peginterferon Alfa-2b Treatment in Patients With Chronic Hepatitis B Based on IFNA2p.Ala120Thr /ISGs Gene Spectrum.

Anticipated Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Comparator:NAs group Active Comparator:nucleotide analogues(NAs) patients continue to use NAs	Drug: Nucleotide Analog such as Entecavir,entecavir 0.5mg per day Other Names: Nucleotide Analogs
Experimental: Experimental:PEG-IFN group Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a	Drug: Interferon Alfa-2A Peginterferon alfa-2a 180ug per week Other Names: Pegasys

Arm

Intervention/Treatment

Active Comparator: Active Comparator:NAs group

Active Comparator:nucleotide analogues(NAs) patients continue to use NAs

Drug: Nucleotide Analog

such as Entecavir,entecavir 0.5mg per day

Other Names:

Nucleotide Analogs

Experimental: Experimental:PEG-IFN group

Experimental: peg-interferon alfa-2a patients switch to sequential peg-interferon α-2a

Drug: Interferon Alfa-2A

Peginterferon alfa-2a 180ug per week

Other Names:

Pegasys

Outcome Measures

Primary Outcome Measures

HBsAg clearance rate [48 weeks]
Whether the HBsAg clearance rate of patients who received interferon treatment was higher than those treated with nucleoside drugs.

Secondary Outcome Measures

HBV cccDNA and pgRNA quantification dynamic change [48 weeks]
The difference in cccDNA and pgRNA clearance rate between the two groups after 48 weeks of treatment in immune-controlled patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18 and 65 years old;
HBsAg positive, HBsAg quantification≤1500 IU/mL;
Serum HBV DNA quantification <100 IU/mL;
HBeAg negative.

Exclusion Criteria:

Treated with interferon in the past six months;
Liver cirrhosis or HCC and other associated tumors;
Women during pregnancy or lactation;
With liver disease caused by other causes;
Combination infection of HIV or other immunodeficiency diseases;
With diabetes, autoimmune diseases and other organ dysfunction or failure;
Combination of other serious complications (infection, hepatic encephalopathy,gastrointestinal bleeding, hepatorenal syndrome, etc.);
Others who cannot be treated with interferon;
Anyone cannot return to the hospital for follow-up and follow-up visits regularly as planned