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Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues (Stop)

Primary Purpose

Chronic Hepatitis B

Status
Unknown status
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Continue NA treatment
Discontinue NA Treatment
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic Hepatitis B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Health NetworkRecruiting
  • University Health NetworkRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Discontinue NA treatment

NA treatment

Arm Description

Subjects will not receive NA during the 72 week study period

Subjects will continue to receive their prescribed NA during the 72 week study period

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
June 25, 2013
Last Updated
May 27, 2015
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT01911156
Brief Title
Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues
Acronym
Stop
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

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
July 2013 (undefined)
Primary Completion Date
January 2016 (Anticipated)
Study Completion Date
March 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Discontinue NA treatment
Arm Type
Other
Arm Description
Subjects will not receive NA during the 72 week study period
Arm Title
NA treatment
Arm Type
Other
Arm Description
Subjects will continue to receive their prescribed NA during the 72 week study period
Intervention Type
Drug
Intervention Name(s)
Continue NA treatment
Intervention Description
Prescribed NA during the 72 week study period
Intervention Type
Drug
Intervention Name(s)
Discontinue NA Treatment
Intervention Description
Discontinue NA Treatment
Primary Outcome Measure Information:
Title
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
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Harry Janssen, MD
Phone
416-603-5986
Email
harry.janssen@uhn.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Victor Lo, MASc, CCRP
Phone
416-603-5839
Email
victor.lo@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harry Janssen, Prof.
Organizational Affiliation
University Heath Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victor Lo, MASc, CCRP
Phone
416-603-5839
Email
victor.lo@uhn.ca
First Name & Middle Initial & Last Name & Degree
Ambreen Arif
First Name & Middle Initial & Last Name & Degree
Harry Janssen, MD
First Name & Middle Initial & Last Name & Degree
Hemant Shah, MD
First Name & Middle Initial & Last Name & Degree
David Wong, MD
First Name & Middle Initial & Last Name & Degree
Jordan Feld, MD
First Name & Middle Initial & Last Name & Degree
Scott Fung, MD
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victor Lo
Phone
416-603-5839
Email
victor.lo@uhn.ca
First Name & Middle Initial & Last Name & Degree
Ambreen Arif
Email
Ambreen.Arif@uhnresearch.ca
First Name & Middle Initial & Last Name & Degree
Harry Janssen, Prof.

12. IPD Sharing Statement

Citations:
PubMed Identifier
31462554
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.
Results Reference
derived

Learn more about this trial

Sustained Off-treatment Response After HBeAg Loss in Chronic Hepatitis B Patients Treated With Nucleos(t)Ide Analogues

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