PEG-IFN in HBV Patients With Incomplete Response to NA

Chronic Hepatitis B Clinical Trial

— PADD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00883844
• Other study ID #: HBV09-03
• Status: Completed
• Phase: Phase 4
• First received: April 17, 2009
• Last updated: April 18, 2013
• Start date: April 2009
• Est. completion date: August 2012

Study information

• Verified date: April 2013
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: August 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

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 B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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
• Nucleos(t)ide analogue treatment
Treatment with one of the approved nucleos(t)ide analogues

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam
Netherlands	Erasmus MC, University Medical Center Rotterdam	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Liver Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained response defined as HBeAg loss and HBV DNA level < 200 IU/mL		at week 72	No