Clinical trial NCT01911156: Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
Official title: Sustained Off-treatment Response After HBeAg Loss in HBeAg-Pos Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Chronic Hepatitis B
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2013-07-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Chronic infection with the hepatitis B virus (HBV) is prevalent world-wide (estimated to affect 360 million individuals).

Chronic hepatitis b may result in progressive liver disease that leads to cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Chronic hepatitis B can also be benign and non-progressive, evolving into an inactive carrier state that rarely leads to significant liver injury or HCC. Over the last few years, several highly effective antiviral agents have been developed and approved for use in the treatment of chronic hepatitis B. Current therapy of chronic hepatitis B (CHB) aims at stopping progression to cirrhosis and hepatocellular carcinoma.

This is a prospective randomized, open-label, phase IV clinical trial to learn the effects, good and/or bad, of discontinuing or continuing 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Heath Network
name: Harry Janssen, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liem 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.