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Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients (STOP)

Primary Purpose

Chronic Hepatitis B.

Status
Unknown status
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
Nucleoside Analogue therapy
Sponsored by
St Vincent's Hospital Melbourne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or Female, age >18 years
  • Subjects must be able to understand and agree to comply with the prescribed intervention (NA cessation), visits and reliably communicate with study personal about adverse events
  • Able to provide informed consent.
  • Chronic Hepatitis B virus infection
  • HBeAg negative at time if initiation of NA therapy
  • Meet current APASL guidelines for consideration of antiviral cessation:
  • uninterrupted NA treatment for >2 years and
  • undetectable serum HBV DNA on three separate occasions >= 6 months apart (undetectable defined by a value < lower limit of detection using a sensitive commercial PCR assay)
  • Normal serum ALT levels (according to the uppers limit of normal of the local laboratory)
  • Minimal to moderate liver fibrosis defined as:
  • METAVIR liver fibrosis stage F0-F3 inclusive prior to initial NA therapy and/or
  • Transient liver elastogram (TLE) (Fibroscan) < /= 9.6 kPa at screening

Exclusion Criteria:

  • HBeAg positive chronic hepatitis B at the time of NA initiation
  • HBV associated extra hepatic manifestations
  • Documented or suspected hepatocellular carcinoma (HCC)
  • History of decompensated liver disease
  • Compensated cirrhosis defined as:
  • METAVIR liver fibrosis stage 4 on pre-treatment biopsy; OR
  • TLE > 9.6 kPa at screening
  • Co-infection with HIV,HCV or HDV
  • Latrogenic or disease related immunosuppression (e.g. treatment with systemic glucocorticoids, TNFa-antibodies, and other immunosuppressive drugs)
  • Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men)
  • Current known history of cancer within 5 years of screening
  • Pregnant or breast feeding
  • Other known significant liver disease (including but not limited to haemochromatosis, autoimmune hepatitis, alcoholic liver disease)
  • Participation in any other interventional trial
  • Poor Venous access
  • Suspected lack of compliance
  • Any medical or social reason which in the opinion of the investigator would make the subject inappropriate for the study

Sites / Locations

  • St Vincent's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nucleoside analogue therapy cessation

Arm Description

To determine if a sustained virological response can be achieved after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.

Outcomes

Primary Outcome Measures

The primary aim of this study is to evaluate the rate of sustained virological response among HBeAg-negative chronic hepatitis B patients who discontinue long-term NA therapy. The outcome is to be assessed by serum assay.

Secondary Outcome Measures

To identify novel immunological determinants of SVR, the assessment will be by serum assay.

Full Information

First Posted
October 15, 2015
Last Updated
October 12, 2016
Sponsor
St Vincent's Hospital Melbourne
Collaborators
National Health and Medical Research Council, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT02581033
Brief Title
Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients
Acronym
STOP
Official Title
Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2014 (undefined)
Primary Completion Date
May 2018 (Anticipated)
Study Completion Date
May 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St Vincent's Hospital Melbourne
Collaborators
National Health and Medical Research Council, Australia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Evaluation of the rate of sustained virological response among HBeAg-negativechronic hepatitis B patients who discontinue long-term NA therapy. During this study participants will cease their prescribed medications, this will occur with immediate effect once enrolled into the study. The duration of cessation will be indefinite, unless clinically indicated for NA therapy re-start. Participants will be monitored as per protocol following cessation, monitoring will be by clinic visit and through blood test to monitor virological response. Clinical visits will be at the intervals of week 2, week, 4, week 8, week 12, week 18, following this they will be every 3 months out to 2 years when the participant will have completed the trial. Once the participant has completed the trial they will not commence again, the aim is for an indefinite cessation of NA therapy.
Detailed Description
During this study participants will cease their prescribed medications, this will occur with immediate effect once enrolled into the study. The duration of cessation will be indefinite, unless clinically indicated for NA therapy re-start. Participants will be monitored as per protocol following cessation, monitoring will be by clinic visit and through blood test to monitor virological response. Clinical visits will be at the intervals of week 2, week, 4, week 8, week 12, week 18, following this they will be every 3 months out to 2 years when the participant will have completed the trial. Once the participant has completed the trial they will not commence again, the aim is for an indefinite cessation of NA therapy.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nucleoside analogue therapy cessation
Arm Type
Experimental
Arm Description
To determine if a sustained virological response can be achieved after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.
Intervention Type
Drug
Intervention Name(s)
Nucleoside Analogue therapy
Other Intervention Name(s)
Cessation of Nucleoside Analogue Therapy
Intervention Description
Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.
Primary Outcome Measure Information:
Title
The primary aim of this study is to evaluate the rate of sustained virological response among HBeAg-negative chronic hepatitis B patients who discontinue long-term NA therapy. The outcome is to be assessed by serum assay.
Time Frame
Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years, to observe for virological changes.
Secondary Outcome Measure Information:
Title
To identify novel immunological determinants of SVR, the assessment will be by serum assay.
Time Frame
Patients will be closely followed for 2 years prospectively, at the following time points; 2 weeks post cessation, 4 weeks, 8 weeks, 12 weeks, 18 weeks, then from 6 months the visits will be 3 monthly out to two years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or Female, age >18 years Subjects must be able to understand and agree to comply with the prescribed intervention (NA cessation), visits and reliably communicate with study personal about adverse events Able to provide informed consent. Chronic Hepatitis B virus infection HBeAg negative at time if initiation of NA therapy Meet current APASL guidelines for consideration of antiviral cessation: uninterrupted NA treatment for >2 years and undetectable serum HBV DNA on three separate occasions >= 6 months apart (undetectable defined by a value < lower limit of detection using a sensitive commercial PCR assay) Normal serum ALT levels (according to the uppers limit of normal of the local laboratory) Minimal to moderate liver fibrosis defined as: METAVIR liver fibrosis stage F0-F3 inclusive prior to initial NA therapy and/or Transient liver elastogram (TLE) (Fibroscan) < /= 9.6 kPa at screening Exclusion Criteria: HBeAg positive chronic hepatitis B at the time of NA initiation HBV associated extra hepatic manifestations Documented or suspected hepatocellular carcinoma (HCC) History of decompensated liver disease Compensated cirrhosis defined as: METAVIR liver fibrosis stage 4 on pre-treatment biopsy; OR TLE > 9.6 kPa at screening Co-infection with HIV,HCV or HDV Latrogenic or disease related immunosuppression (e.g. treatment with systemic glucocorticoids, TNFa-antibodies, and other immunosuppressive drugs) Significant alcohol consumption (> 30 g/day for women and > 50 g/day for men) Current known history of cancer within 5 years of screening Pregnant or breast feeding Other known significant liver disease (including but not limited to haemochromatosis, autoimmune hepatitis, alcoholic liver disease) Participation in any other interventional trial Poor Venous access Suspected lack of compliance Any medical or social reason which in the opinion of the investigator would make the subject inappropriate for the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gareth Burns, MD
Phone
+61309231 3581
Email
gareth.burns@svha.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Thompson, MD
Organizational Affiliation
St Vincent's Hospital Melbourne
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gareth Burns, MD
Phone
+61392313581
Email
gareth.burns@svha.org.au
First Name & Middle Initial & Last Name & Degree
John Gough, RN
Phone
+61392313518
Email
john.gough@svha.org.au

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients

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