Halting Nucleoside Analogues in Chronic Hepatitis B

NCT04102176 | Active Not Recruiting DMC

• 1 other identifier: CIRG17may042
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Most patients with Chronic Hepatitis B are on nucleoside analogy (NA) long term, but this leads to HBsAg loss (defined as functional cure) of only 2% at 6 years. Recently a number of studies have shown significant HBsAg loss rates after stopping nucleoside analogues (NA). However, no criteria to select such patients have been evaluated. Consequently, the objective of the study is not only to determine the proportion of patients able to achieve HBsAg loss in those with qHBsAg≤100IU/ml. The study is designed as a randomised control trial with 1:2 parallel arm randomisation to continuing NA or stopping therapy. Patients will be monitored after stopping therapy for Hepatitis B flares and also to document HBsAg loss.

Conditions

Chronic Hepatitis B

Keywords

chronic hepatitis B; nucleoside analogues; stopping; discontinuing

Outcome Measures

Primary Outcomes (1)

• HBsAg loss

  Absence of HBsAg by ELISA

  Through year 3

Secondary Outcomes (3)

• Hepatitis B flare

  Through year 3

• virological relapse

  Through year 3

• Restarting antiviral therapy

  Through year 3

Study Arms (2)

Continue nucleos(t)ide analogue

ACTIVE COMPARATOR

patients will be given open label tenofovir alafenamide

Other: Continue nucleos(t)ide analogue

Stopping nucleos(t)ide analogue

EXPERIMENTAL

patients will stop nucleos(t)ide therapy (such as entecavir, tenofovir, lamivudine or adefovir)

Other: stopping nucleos(t)ide therapy

Interventions

stopping nucleos(t)ide therapy OTHER

patients taking nucleoside(t)ide therapy will stop treatment

Stopping nucleos(t)ide analogue

Continue nucleos(t)ide analogue OTHER

Continue nucleos(t)ide analogue

Continue nucleos(t)ide analogue

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 21 and 75 years old.
• Documented to be HBsAg positive for ≥ 6 months.
• On any NA (lamivudine, adefovir, entecavir, telbivudine tenofovir) for ≥ 1 year
• HBV DNA \<15 IU/ml at screening (undetectable)
• Quantitative HBsAg \<100 IU/ml
• Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
• Patient is able to give written consent prior to study start and to comply with the study requirements.
• Women of childbearing age must have a negative serum (ß-HCG) pregnancy test taken with 14 days of starting therapy

You may not qualify if:

• Evidence of liver cirrhosis based on liver biopsy, fibroscan score \>10.5 kpa, or MRE score\>5.5kpa, or clinical evidence of cirrhosis demonstrated by presence of esophageal varices, obvious features of cirrhosis on ultrasound within the last 12 months
• Evidence of decompensated liver disease or hepatocellular carcinoma.
• HIV antibody or HCV antibody or HDV antibody positivity
• Creatinine \> 1.5 times upper limit of normal
• INR \> 1.5, uncorrected by Vitamin K therapy.
• Any interferon, Immunomodulators, systemic cytotoxic agents, or systemic corticosteroids within 6 months before trial entry.
• Prolonged exposure to known hepatotoxins such as alcohol or drugs.
• History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, hematological disease or medical illness that in the investigator's opinion might interfere with therapy.
• Malignant disease within 5 years of trial entry.
• Women who are pregnant and who are not practicing adequate birth control measures, or who are lactating

Sponsors & Collaborators

• Seng Gee Lim: lead
• Tan Tock Seng Hospital: collaborator
• Singapore General Hospital: collaborator
• Changi General Hospital: collaborator

Study Sites (1)

National University Hospital

Singapore, 119228, Singapore

Location

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

• Seng Gee Lim, MBBS MD

  National University Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Hepatology

Model Details: Parallel arm study randomised 1:2

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: September 25, 2019
• Study Start: January 29, 2019
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)