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

NCT02581033 | Unknown DMC

• 1 other identifier: 032/14 Protocol # :APP106653
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B.

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (1)

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

  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.

Study Arms (1)

Nucleoside analogue therapy cessation

EXPERIMENTAL

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

Drug: Nucleoside Analogue therapy

Interventions

Nucleoside Analogue therapy DRUG

Determinants of sustained virological response after discontinuation of long-term nucleoside analogue therapy in chronic hepatitis B patients.

Also known as: Cessation of Nucleoside Analogue Therapy

Nucleoside analogue therapy cessation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St Vincent's Hospital Melbourne: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

St Vincent's Hospital

Melbourne, Victoria, 3065, Australia

RECRUITING

Related Publications (1)

• Hume SJ, Hall S, Burns G, Vogrin S, Tassone D, Desmond P, Ratnam D, Levy MT, Sawhney R, Nicoll A, Valaydon Z, Strasser SI, Ngu M, Sinclair M, Meredith C, Matthews GV, Visvanathan K, Holmes JA, Thompson AJ. Long-Term Follow-Up of Patients in a Prospective Study of NA Discontinuation Identifies Different Patterns of HBsAg Loss. Aliment Pharmacol Ther. 2026 Jan;63(2):231-241. doi: 10.1111/apt.70332. Epub 2025 Aug 21.

  PMID: 40842267 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexander Thompson, MD

  St Vincent's Hospital Melbourne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gareth Burns, MD

CONTACT

+61309231 3581; gareth.burns@svha.org.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: October 20, 2015
• Study Start: May 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: October 14, 2016

Record last verified: 2016-10

Locations

AU (1)