Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
Stop
2 other identifiers
interventional
66
1 country
2
Brief Summary
This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing nucleos(t)ide analogue (NA) treatment for 72 weeks in participants with chronic hepatitis B infection whose immune system is controlling the amount of virus levels in the blood for at least 12 months of NA therapy. About 66 adult men and women will participate in this study from University Health Network which includes the Toronto Western Hospital for about 72 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Jul 2013
Typical duration for phase_4
2 active sites
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
June 25, 2013
CompletedStudy Start
First participant enrolled
July 1, 2013
CompletedFirst Posted
Study publicly available on registry
July 30, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2016
CompletedMay 28, 2015
May 1, 2015
2.5 years
June 25, 2013
May 27, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Sustained response, defined as the presence of an HBV DNA level <2000 IU/ml at week 48 in patients with a combined response at baseline
Outcome of patients in whom NA monotherapy is stopped at week 0 and of patients who continue to receive NA monotherapy up till week 72
Study Arms (2)
Discontinue NA treatment
OTHERSubjects will not receive NA during the 72 week study period
NA treatment
OTHERSubjects will continue to receive their prescribed NA during the 72 week study period
Interventions
Eligibility Criteria
You may qualify if:
- Chronic hepatitis B (HBsAg positive \> 6 months)
- Currently on NA monotherapy and for ≥1 year prior to screening
- HBeAg negative with anti-HBe antibodies and HBV DNA undetectable at least once at 12 or more months prior to screening and at screening (HBV DNA assay should have lower limit of quantification of at least 50 IU/mL)
- Documented HBeAg positive before start of NA monotherapy
- Age \> 18 years
- Written informed consent
You may not qualify if:
- Treatment with any investigational drug within 30 days of screening
- Severe hepatitis activity as documented by ALT \>10x ULN
- Creatinine clearance \<70 ml/min
- Presence of cirrhosis as documented by biopsy within 5 years, fibroscan \>9kPa, or fibrotest \>0.48
- Pre-existent neutropenia (neutrophils ≤1,000/mm3)
- Co-infection with hepatitis C virus and/or human immunodeficiency virus (HIV)
- Other acquired or inherited causes of liver disease
- Alpha fetoprotein \>50 ng/ml
- Hyper- or hypothyroidism
- Immune suppressive treatment within the previous 6 months
- Pregnancy, lactation
- Other significant medical illnesses that might interfere with this study
- Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
- Substance abuse (alcohol (≥80 g/day)and inhaled drugs (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 (2)
University Health Network
Toronto, Ontario, M5T 2S8, Canada
University Health Network
Toronto, Ontario, M5T 2S8, Canada
Related Publications (3)
Dongelmans EJ, Feld JJ, Boonstra A, Brakenhoff SM, Wong D, Yim C, Claassen M, Honkoop P, Hansen BE, de Man RA, Fung S, Berg T, van Bommel F, Janssen HLA, Sonneveld MJ. Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation-A Pooled Analysis of Two Clinical Trials. Aliment Pharmacol Ther. 2025 Feb;61(3):570-578. doi: 10.1111/apt.18416. Epub 2024 Dec 3.
PMID: 39624922DERIVEDLiem KS, Chi H, Fung S, Wong DK, Yim C, Noureldin S, Chen J, de Man RA, Sarowar A, Feld JJ, Hansen BE, Hou J, Peng J, Janssen HLA. Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B. J Viral Hepat. 2022 Nov;29(11):986-993. doi: 10.1111/jvh.13742. Epub 2022 Sep 14.
PMID: 36048970DERIVEDLiem KS, Fung S, Wong DK, Yim C, Noureldin S, Chen J, Feld JJ, Hansen BE, Janssen HLA. Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study). Gut. 2019 Dec;68(12):2206-2213. doi: 10.1136/gutjnl-2019-318981. Epub 2019 Aug 28.
PMID: 31462554DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Harry Janssen, Prof.
University Heath Network
Central Study Contacts
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
June 25, 2013
First Posted
July 30, 2013
Study Start
July 1, 2013
Primary Completion
January 1, 2016
Study Completion
March 1, 2016
Last Updated
May 28, 2015
Record last verified: 2015-05