Lowering Viral Load With Nucleos(T)Ide Analogues Prior to Peginterferon Treatment to Ncrease Sustained Response in CHB

Phase 4

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: PegIFN alfa-2b

• Registration Number: NCT01532843
• Lead Sponsor: Foundation for Liver Research

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-02-10
• Study First Submitted QC: 2012-02-14
• Study First Posted: 2012-02-15
• Study Start: 2012-06
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-03
• Last Update Posted: 2019-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Chronic hepatitis B (HBsAg positive > 6 months)
• HBeAg positive, anti-HBe negative within 4 weeks prior to initiation of peginterferon alfa-2b
• HBV DNA < 2000 IU/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either Entecavir (one of all 3 brands) or Tenofovir
• ALT < 5x ULN
• Compensated liver disease
• Age ≥ 18 years and ≤ 70 years
• Written informed consent

Exclusion Criteria

• Treatment with any investigational drug within 30 days of entry to this protocol
• Treatment with Telbivudine
• Severe hepatitis activity as documented by ALT > 5 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 < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
• Co-infection with hepatitis C 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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PegIFN alfa-2b + nucleos(t)ide analogue	PegIFN alfa-2b	Peginterferon alfa-2b 1.5 μg/kg per week s.c. for 48 weeks in addition to standard nucleos(t)ide analogue treatment

Primary Outcome Measures

Name	Time	Method
Sustained response	at week 72	Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA \< 200 IU/mL

Trial Locations

Locations (4)

Ruijin Hospital "Jiaolong University"; 🇨🇳 Shanghai, China

Erasmus MC, University Medical Center; 🇳🇱 Rotterdam, Netherlands

Zhong Shan Hospital "Fu Dan University"; 🇨🇳 Shanghai, China

Public Health Center "Fu Dan University"; 🇨🇳 Shanghai, China