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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01769833
• Other study ID #: ML25659
• Status: Active, not recruiting
• Phase: Phase 3
• First received: January 15, 2013
• Last updated: November 3, 2014
• Start date: May 2013
• Est. completion date: May 2016

Study information

• Verified date: November 2014
• Source: Pusan National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 144
• Est. completion date: May 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• PEG-interferon-Alfa-2A
Pegasys ( PEG-interferon-Alfa-2A) 180mcg / subcutaneous / once-weekly
• Nucleosides

Locations

Country	Name	City	State
Korea, Republic of	Pusan National University Hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Pusan National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	effect of immune modulator therapy on the innate immune response in patients with HBeAg-positive CHB	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.	48 week, 96 week	No
Primary	Change in log10 HBsAg titer during antiviral therapy	To evaluate whether pegylated-IFNa2a treatment lowers HBsAg levels and eventually leads to HBsAg loss in patients after long term NA therapy compared to continuing NA treatment.	48 week	No
Secondary	HBV DNA undetectability and below 400 IU/mL during antiviral therapy and follow-up		48 week, 96 week	No
Secondary	HBeAg seroconversion and loss during antiviral therapy and at end of treatment and 1 and 2 years following end of treatment		48 week, 96 week	No
Secondary	HBsAg loss and HBsAg seroconversion at end of treatment and 1 and 2 years following end of treatment		48 week, 96 week	No
Secondary	Change in log10 HBsAg titer during follow-up		48 week, 96 week	No
Secondary	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		48 week	No