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

NCT ID: NCT01532843

Last Updated: 2019-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2015-08-31

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

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PegIFN alfa-2b + nucleos(t)ide analogue

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

Group Type: ACTIVE_COMPARATOR

PegIFN alfa-2b

Intervention Type: DRUG

Peginterferon alpha-2b 1.5 μg/kg per week s.c.for 48 weeks

Nucleos(t)ide analogue

Continuation of Nucleos(t)ide analogue mono-therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

PegIFN alfa-2b

Peginterferon alpha-2b 1.5 μg/kg per week s.c.for 48 weeks

Intervention Type: DRUG

Other Intervention Names

Pegintron

Eligibility Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Liver Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harry LA Janssen, MD PHD

Role: PRINCIPAL_INVESTIGATOR

Erasmus MC, University Medical Center Rotterdam

Locations

Ruijin Hospital "Jiaolong University"

Shanghai, , China

Public Health Center "Fu Dan University"

Shanghai, , China

Zhong Shan Hospital "Fu Dan University"

Shanghai, , China

Erasmus MC, University Medical Center

Rotterdam, , Netherlands

Countries

China; Netherlands

References

Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.

Reference Type: DERIVED

PMID: 35599306 (View on PubMed)

Liem KS, van Campenhout MJH, Xie Q, Brouwer WP, Chi H, Qi X, Chen L, Tabak F, Hansen BE, Janssen HLA. Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098.

Reference Type: DERIVED

PMID: 30689258 (View on PubMed)

Chi H, Hansen BE, Guo S, Zhang NP, Qi X, Chen L, Guo Q, Arends P, Wang JY, Verhey E, de Knegt RJ, Xie Q, Janssen HLA. Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON). J Infect Dis. 2017 Apr 1;215(7):1085-1093. doi: 10.1093/infdis/jix024.

Reference Type: DERIVED

PMID: 28329061 (View on PubMed)

Other Identifiers

HBV 11-02

Identifier Type: -

Identifier Source: org_study_id