NCT01532843

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jun 2012

Typical duration for phase_4

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 15, 2012

Completed
4 months until next milestone

Study Start

First participant enrolled

June 1, 2012

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
Last Updated

January 4, 2019

Status Verified

January 1, 2019

Enrollment Period

3.2 years

First QC Date

February 10, 2012

Last Update Submit

January 3, 2019

Conditions

Chronic Hepatitis B

Keywords

Hepatitis Bsustained responsepeginterferonnucleos(t)ide analogues

Outcome Measures

Primary Outcomes (1)

  • Sustained response

    Sustained response to therapy, defined as the combined presence of HBeAg seroconversion and HBV DNA \< 200 IU/mL

    at week 72

Study Arms (2)

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

ACTIVE COMPARATOR

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

Drug: PegIFN alfa-2b

Nucleos(t)ide analogue

NO INTERVENTION

Continuation of Nucleos(t)ide analogue mono-therapy

Interventions

PegIFN alfa-2bDRUG

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

Also known as: Pegintron
PegIFN alfa-2b + nucleos(t)ide analogue

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Ruijin Hospital "Jiaolong University"

Shanghai, 200025, China

Location

Public Health Center "Fu Dan University"

Shanghai, 200083, China

Location

Zhong Shan Hospital "Fu Dan University"

Shanghai, 200083, China

Location

Erasmus MC, University Medical Center

Rotterdam, Netherlands

Location

Related Publications (3)

  • 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.

    PMID: 35599306DERIVED

  • 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.

    PMID: 30689258DERIVED

  • 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.

    PMID: 28329061DERIVED

MeSH Terms

Conditions

Hepatitis B, ChronicHepatitis B

Interventions

peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Harry LA Janssen, MD PHD

    Erasmus MC, University Medical Center Rotterdam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2012

First Posted

February 15, 2012

Study Start

June 1, 2012

Primary Completion

August 1, 2015

Study Completion

August 1, 2015

Last Updated

January 4, 2019

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will not share

Locations

CN(3)NL(1)