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

NCT ID: NCT01911156

Last Updated: 2015-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2016-03-31

Brief Summary

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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

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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.

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Discontinue NA treatment

Subjects will not receive NA during the 72 week study period

Group Type OTHER

Discontinue NA Treatment

Intervention Type DRUG

Discontinue NA Treatment

NA treatment

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

Group Type OTHER

Continue NA treatment

Intervention Type DRUG

Prescribed NA during the 72 week study period

Interventions

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Continue NA treatment

Prescribed NA during the 72 week study period

Intervention Type DRUG

Discontinue NA Treatment

Discontinue NA Treatment

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Harry Janssen, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Heath Network

Locations

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University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Harry Janssen, MD

Role: CONTACT

416-603-5986

Victor Lo, MASc, CCRP

Role: CONTACT

416-603-5839

Facility Contacts

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Victor Lo, MASc, CCRP

Role: primary

416-603-5839

Victor Lo

Role: primary

416-603-5839

Ambreen Arif

Role: backup

References

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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.

Reference Type DERIVED
PMID: 39624922 (View on PubMed)

Liem 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.

Reference Type DERIVED
PMID: 36048970 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31462554 (View on PubMed)

Other Identifiers

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GILEAD Sciences Canada, Inc.

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Stop Study

Identifier Type: -

Identifier Source: org_study_id

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