The Optimizing Treatment of Peginterferon Alpha in Chronic Hepatitis B Patients With Low Level HBsAg

NCT ID: NCT03801538

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2020-12-31

Brief Summary

HBeAg-negative chronic hepatitis B (CHB) patients with low Level HBsAg were enrolled. After giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/ mL). Depending on the decline of HBsAg level, treatment was either continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. After treatment, all patients were followed up for 48 weeks.

②If the decrease of HBsAg is less than 50% compared to baseline level. The combination therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg was evaluated again.

If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/mL). Depending on the decline of HBsAg level, treatment was either continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. After treatment, all patients were followed up for 48 weeks.

If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

Patients who maintained the original NAs treatment served as a control group.

Detailed Description

It is estimated that more than 400 million people are infected with hepatitis B virus (HBV) globally. HBeAg-negative CHB patients with low Level HBsAg were enrolled in the out-patient department of Third Affiliated Hospital of Sun Yat-sen University and Wuhan Union Hospital. All of them were HBsAg positive and anti-HBs negative for more than 6 months with HBV DNA<100 IU/mL and HBsAg levels <1000 IU/mL. All patients did not have other liver diseases and contraindications for interferon therapy. After giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/ mL). Depending on the decline of HBsAg level, treatment was either continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. After treatment, all patients were followed up for 48 weeks.

②If the decrease of HBsAg is less than 50% compared to baseline level. The combination therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg was evaluated again.

If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(<0.05 IU/mL). Depending on the decline of HBsAg level, treatment was either continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. After treatment, all patients were followed up for 48 weeks.

If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

The use of other immune suppressive or regulatory drugs and other antiviral drugs was prohibited during the course of the study. In this study, HBsAg loss(<0.05 IU/mL) was defined as treatment endpoint. Anti-HBs positive(>10 milli-International unit)(mIU/mL) was defined as seroconversion.

Patients who maintained the original NAs treatment served as a control group.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PEG-IFN group

patients were treated with NAs once a day and PEG-IFN once a week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

①If the decrease of HBsAg is more than 50%. NAs was stopped. PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96.

②If the decrease of HBsAg is less than 50%.NAs and PEG-IFN was extended to week 24. Then, If the decrease of HBsAg is more than 50%. NAs was stopped, PEG-IFN Treatment was continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in week 96. If the decrease of HBsAg is less than 50%. PEG-IFN was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

Group Type: EXPERIMENTAL

Peginterferon Alfa

Intervention Type: DRUG

Peginterferon Alfa-2A 180 micrograms/week or Peginterferon Alfa-2B 180 micrograms/week, for at most 96 weeks.

NAs group

CHB patients do not need to change their NAs treatment.

Group Type: OTHER

Nucleoside Analog (Substance)

Intervention Type: DRUG

Patients do not need to change their NAs treatment.

Interventions

Peginterferon Alfa

Peginterferon Alfa-2A 180 micrograms/week or Peginterferon Alfa-2B 180 micrograms/week, for at most 96 weeks.

Intervention Type: DRUG

Nucleoside Analog (Substance)

Patients do not need to change their NAs treatment.

Intervention Type: DRUG

Other Intervention Names

PEG-IFN; NAs

Eligibility Criteria

Inclusion Criteria

1. CHB patients who had received NAs for more than 12 months.

2. Hepatitis B e antigen (HBeAg)-negative.

3. Hepatitis B surface antigen (HBsAg) positive and <1000 IU/mL.

4. Hepatitis B virus DNA <100 IU/mL.

Exclusion Criteria

1. Patients with liver cirrhosis, Hepatocellular Carcinoma or alpha feto protein (AFP) >2 upper limit of normal(ULN) or other malignancies.

2. Patients with other factors causing liver diseases.

3. Pregnant and lactating women.

4. Patients with concomitant HIV infection or congenital immune deficiency diseases.

5. Patients with diabetes, autoimmune diseases.

6. Patients with important organ dysfunctions.

7. Patients with serious complications (e.g., infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding.)

8. Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months.

9. Patients who can't come back to clinic for follow-up on schedule.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Zhiliang Gao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhiliang Gao

Role: PRINCIPAL_INVESTIGATOR

Third Affiliated Hospital, Sun Yat-Sen University

Locations

Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

I-Cure-3X

Identifier Type: -

Identifier Source: org_study_id