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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02581033




Registration number
NCT02581033
Ethics application status
Date submitted
15/10/2015
Date registered
20/10/2015
Date last updated
14/10/2016

Titles & IDs
Public title
Determinants of Virological Response After Discontinuation of Nucleoside Analogue Therapy in Hepatitis B Patients
Scientific title
Determinants of Sustained Virological Response After Discontinuation of Long-term Nucleoside Analogue Therapy in Chronic Hepatitis B Patients
Secondary ID [1] 0 0
032/14 Protocol # :APP106653
Universal Trial Number (UTN)
Trial acronym
STOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B. 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nucleoside Analogue therapy

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


Treatment: Drugs: Nucleoside Analogue therapy
Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 [1] 0 0
To identify novel immunological determinants of SVR, the assessment will be by serum assay.
Timepoint [1] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3065 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
St Vincent's Hospital Melbourne
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02581033
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alexander Thompson, MD
Address 0 0
St Vincent's Hospital Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gareth Burns, MD
Address 0 0
Country 0 0
Phone 0 0
+61309231 3581
Fax 0 0
Email 0 0
gareth.burns@svha.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02581033