PADD: PEG-IFN in HBV Patients With Incomplete Response to NA

Sponsor

Foundation for Liver Research (Other)

Overall Status

Completed

CT.gov ID

NCT00883844

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings.

The aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Nucleos(t)ide analogue treatment with a peginterferon add-on strategy Drug: Nucleos(t)ide analogue treatment	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Lowering Viral Load With Nucleos(t)Ide Analogues Prior to Peginterferon Alfa-2b Treatment to Increase Sustained Response in HBeAg-positive Chronic Hepatitis B - a Pilot Study

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Continuation of any Nucleos(t)ide analogue treatment and add-on of peginterferon for 24 weeks	Drug: Nucleos(t)ide analogue treatment with a peginterferon add-on strategy peginterferon 1.5 microgram/kg once a week Treatment with one of the approved nucleos(t)ide analogues
Active Comparator: 2 Continuation of Nucleos(t)ide analogue mono-therapy	Drug: Nucleos(t)ide analogue treatment Treatment with one of the approved nucleos(t)ide analogues

Arm

Intervention/Treatment

Experimental: 1

Continuation of any Nucleos(t)ide analogue treatment and add-on of peginterferon for 24 weeks

Drug: Nucleos(t)ide analogue treatment with a peginterferon add-on strategy

peginterferon 1.5 microgram/kg once a week Treatment with one of the approved nucleos(t)ide analogues

Active Comparator: 2

Continuation of Nucleos(t)ide analogue mono-therapy

Drug: Nucleos(t)ide analogue treatment

Treatment with one of the approved nucleos(t)ide analogues

Outcome Measures

Primary Outcome Measures

Sustained response defined as HBeAg loss and HBV DNA level < 200 IU/mL [at week 72]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Chronic hepatitis B (HBsAg positive > 6 months)
HBeAg positive, anti-HBe negative within one month prior to initiation of peginterferon alfa-2b
HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peginterferon alfa-2b
Compensated liver disease
Age > 18 years
Written informed consent

Exclusion Criteria:

Treatment with any investigational drug within 30 days of entry to this protocol
Severe hepatitis activity as documented by ALT>10 x ULN
History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
Pre-existent neutropenia (neutrophils <1,800/mm3) or thrombocytopenia (platelets <90,000/mm3)
Co-infection with hepatitis C virus, hepatitis D virus or human immunodeficiency virus (HIV)
Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency
Alpha fetoprotein > 50 ng/ml
Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
Immune suppressive treatment within the previous 6 months
Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or Peginterferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
Pregnancy, breast-feeding
Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
Substance abuse, such as alcohol (>80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study