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HBsAg Decline After Pegylated-interferon-α in e Antigen Positive Chronic Hepatitis B With Nucleoside Maintenance

Primary Purpose

Chronic Hepatitis B

Status

Unknown status

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

PEG-interferon-Alfa-2A

Nucleosides

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring HBsAg, Chronic hepatitis B, PEGinterferon Alfa-2A

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Informed consent
Age over 20 years
HBeAg-positive CHB patients
Patients treated with all available nucleoside analogue monotherapy or combination in Korea except telbivudine ( e.g.entecavir monotherapy or lamivudine/adefovir combination , lamivudine, adefovir monotherapy) for ≥ 18months and patients who have undetectable HBV viral load at least one year HBV DNA undetectable (≤ 400 copies/ml ) Serum alanine transferase: ≤ 10 X upper limit of normal (ULN) Baseline HBsAg: ≥ 102 IU/ml
Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion.
Obtaining written informed consent form

Exclusion Criteria:

Decompensated cirrhosis or other contraindications to interferon alfa 2a therapy following local label.
Concomitant or prior use of telbivudine.
Positive test at screening for hepatitis A virus immunoglobulin M Ab, Hepatitis C virus-RNA or hepatitis C virus Ab, hepatitis delta virus Ab or HIV Ab.
Diagnosed hepatic cellular carcinoma
Any evidence of decompensated liver disease (Childs B-C)
History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).
Women with ongoing pregnancy or who are breast feeding.
Evidence of alcohol and/or drug abuse within one year of entry.
History of major organ transplantation with an existing functional graft.
Inability or unwillingness to provide informed consent or abide by the requirements of the study.
History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.
patients having hypersensitivities for peginterferon alfa-2a or NAs

Sites / Locations

Pusan National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

PEG-interferon-alfa 2A

Nucleosides

Arm Description

PEG-interferon-alfa 2A

Nucleosides

Outcomes

Primary Outcome Measures

Change in log10 HBsAg titer during antiviral therapy

To evaluate whether pegylated-IFNα2a treatment lowers HBsAg levels and eventually leads to HBsAg loss in patients after long term NA therapy compared to continuing NA treatment.

Secondary Outcome Measures

HBV DNA undetectability and below 400 IU/mL during antiviral therapy and follow-up

HBeAg seroconversion and loss during antiviral therapy and at end of treatment and 1 and 2 years following end of treatment

HBsAg loss and HBsAg seroconversion at end of treatment and 1 and 2 years following end of treatment

Change in log10 HBsAg titer during follow-up

Mean change in log10 HBsAg titre over time, as estimated from the area between the baseline value and the curve of log10 HBsAg titre divided by the duration of treatment

Full Information

NCT ID

NCT01769833

First Posted

January 15, 2013

Last Updated

November 3, 2014

Sponsor

Pusan National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01769833

Brief Title

HBsAg Decline After Pegylated-interferon-α in e Antigen Positive Chronic Hepatitis B With Nucleoside Maintenance

Official Title

HBsAg Decline and HBeAg Seroconversion Following 48 Weeks Peg-interferon-α Treatment in Patients With e Antigen Positive Chronic Hepatitis B After Nucleoside Analogue Maintenance Therapy Compared to Continuing Nucleoside Analogue Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Unknown status

Study Start Date

May 2013 (undefined)

Primary Completion Date

May 2015 (Anticipated)

Study Completion Date

May 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pusan National University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study proposes to compare the effect of 48 weeks exposure to pegylated interferon alpha vs. nucleoside analogue (NA) on hepatitis B e antigen (HBeAg) seroconversion and HBsAg levels in nucleoside analogue controlled HBeAg-positive chronic hepatitis B (CHB) patients who have an undetectable hepatitis B virus (HBV) viral load at least 1 years.

Detailed Description

Pegylated interferon after long term NA therapy will potentiate the antiviral efficacy directly via its effect on broad antiviral activities and indirectly via activation of innate and adaptive immune responses leading to HBeAg seroconversion and eventually HBsAg loss and/or seroconversion. This study proposes to compare the effect of 48 weeks exposure to pegylated interferon alpha vs. NA on HBeAg seroconversion and HBsAg levels in NA controlled HBeAg-positive CHB patients who have an undetectable HBV viral load at least 1 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

Keywords

HBsAg, Chronic hepatitis B, PEGinterferon Alfa-2A

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PEG-interferon-alfa 2A

Arm Type

Active Comparator

Arm Description

PEG-interferon-alfa 2A

Arm Title

Nucleosides

Arm Type

Placebo Comparator

Arm Description

Nucleosides

Intervention Type

Drug

Intervention Name(s)

PEG-interferon-Alfa-2A

Other Intervention Name(s)

Pegasys (PEG-interferon-Alfa-2A)

Intervention Description

Pegasys ( PEG-interferon-Alfa-2A) 180mcg / subcutaneous / once-weekly

Intervention Type

Drug

Intervention Name(s)

Nucleosides

Primary Outcome Measure Information:

Title

Change in log10 HBsAg titer during antiviral therapy

Description

To evaluate whether pegylated-IFNα2a treatment lowers HBsAg levels and eventually leads to HBsAg loss in patients after long term NA therapy compared to continuing NA treatment.

Time Frame

48 week

Secondary Outcome Measure Information:

Title

HBV DNA undetectability and below 400 IU/mL during antiviral therapy and follow-up

Time Frame

48 week, 96 week

Title

HBeAg seroconversion and loss during antiviral therapy and at end of treatment and 1 and 2 years following end of treatment

Time Frame

48 week, 96 week

Title

HBsAg loss and HBsAg seroconversion at end of treatment and 1 and 2 years following end of treatment

Time Frame

48 week, 96 week

Title

Change in log10 HBsAg titer during follow-up

Time Frame

48 week, 96 week

Title

Mean change in log10 HBsAg titre over time, as estimated from the area between the baseline value and the curve of log10 HBsAg titre divided by the duration of treatment

Time Frame

48 week

Other Pre-specified Outcome Measures:

Title

effect of immune modulator therapy on the innate immune response in patients with HBeAg-positive CHB

Description

To evaluate the effect of immune modulator therapy on the innate immune response in patients with HBeAg-positive CHB in whom NA treatment has resulted in undetectable viral replication.

Time Frame

48 week, 96 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Informed consent Age over 20 years HBeAg-positive CHB patients Patients treated with all available nucleoside analogue monotherapy or combination in Korea except telbivudine ( e.g.entecavir monotherapy or lamivudine/adefovir combination , lamivudine, adefovir monotherapy) for ≥ 18months and patients who have undetectable HBV viral load at least one year HBV DNA undetectable (≤ 400 copies/ml ) Serum alanine transferase: ≤ 10 X upper limit of normal (ULN) Baseline HBsAg: ≥ 102 IU/ml Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. Obtaining written informed consent form Exclusion Criteria: Decompensated cirrhosis or other contraindications to interferon alfa 2a therapy following local label. Concomitant or prior use of telbivudine. Positive test at screening for hepatitis A virus immunoglobulin M Ab, Hepatitis C virus-RNA or hepatitis C virus Ab, hepatitis delta virus Ab or HIV Ab. Diagnosed hepatic cellular carcinoma Any evidence of decompensated liver disease (Childs B-C) History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia). Women with ongoing pregnancy or who are breast feeding. Evidence of alcohol and/or drug abuse within one year of entry. History of major organ transplantation with an existing functional graft. Inability or unwillingness to provide informed consent or abide by the requirements of the study. History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study. Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. patients having hypersensitivities for peginterferon alfa-2a or NAs

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeong Heo, Dr

Organizational Affiliation

Pusan National University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Pusan National University Hospital

City

Busan

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

35867702

Citation

Woo HY, Heo J, Tak WY, Lee HJ, Chung WJ, Park JG, Park SY, Park YJ, Lee YR, Hwang JS, Kweon YO. Effect of switching from nucleos(t)ide maintenance therapy to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: A randomized trial. PLoS One. 2022 Jul 22;17(7):e0270716. doi: 10.1371/journal.pone.0270716. eCollection 2022.

Results Reference

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HBsAg Decline After Pegylated-interferon-α in e Antigen Positive Chronic Hepatitis B With Nucleoside Maintenance

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