Halting Nucleoside Analogues in Chronic Hepatitis B (HALT-NUCS)

September 24, 2019 updated by: Seng Gee Lim

HALT NUCs: Halting Nucleoside Analogue Therapy in Chronic Hepatitis B

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic Hepatitis B (CHB) affects over 250 million persons and is considered one of the major causes of mortality and morbidity globally. Standard treatment consists of nucleos(t)ide analogues (NA) or peginterferon (PEG). There has been increasing interested in HBsAg loss, defined as functional cure. However this has been difficult to achieve with NA, and although rates of HBsAg loss are higher with PEG, they are still <10%. However, a number of studies have shown that HBsAg loss rates were significantly higher in those who stopped NA. A study from Greece by Hadziyannis had a 39% HBsAg loss after patients stopped adefovir therapy. Further studies have shown similar results, and those not able to clear HBsAg have had quiescent disease, although some patients had to restart therapy usually due to hepatitis B flares. No deaths have been reported. Consequently, while stopping therapy has led to HBsAg loss in some patients, it is not clear which patients would benefit the most. The prior studies have indicated that patients most likely to lose HBsAg had low qHBsAg levels and a level ≤100 IU/ml had a high possibility of HBsAg loss. Consequently, we propose to test whether patients with CHB on NA >1year and without liver cirrhosis and with qHBsAg≤100 IU/ml are able to lose HBsAg compared to those who continue NA. The study is designed as a parallel arm RCT randomised 1:2 to continue NA versus stop NA. Patients will be monitored regularly for clinical status, virological markers, and liver markers. The primary endpoint is HBsAg loss at the end of the study in those who stop versus those who continue NA. Additional outcomes will be hepatitis B flares, inactive hepatitis B status, virological relapse, and restarting therapy.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Singapore
      • Singapore, Singapore, 119228
        • Recruiting
        • National University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • • 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

Exclusion Criteria:

  • • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Continue nucleos(t)ide analogue
patients will be given open label tenofovir alafenamide
Other: Continue nucleos(t)ide analogue
Continue nucleos(t)ide analogue
Experimental: Stopping nucleos(t)ide analogue
patients will stop nucleos(t)ide therapy (such as entecavir, tenofovir, lamivudine or adefovir)
Other: stopping nucleos(t)ide therapy
patients taking nucleoside(t)ide therapy will stop treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBsAg loss
Time Frame: Through year 3
Absence of HBsAg by ELISA
Through year 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatitis B flare
Time Frame: Through year 3
increase in ALT associated with increase in HBV DNA
Through year 3
virological relapse
Time Frame: Through year 3
increase in HBV DNA without increase in ALT
Through year 3
Restarting antiviral therapy
Time Frame: Through year 3
Those who have to start therapy based on clinical indications after stopping therapy
Through year 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seng Gee Lim

Collaborators

Singapore General Hospital
Tan Tock Seng Hospital
Changi General Hospital

Investigators

  • Principal Investigator: Seng Gee Lim, MBBS MD, National University Health System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2019

Primary Completion (Anticipated)

March 1, 2021

Study Completion (Anticipated)

March 30, 2021

Study Registration Dates

First Submitted

May 27, 2019

First Submitted That Met QC Criteria

September 24, 2019

First Posted (Actual)

September 25, 2019

Study Record Updates

Last Update Posted (Actual)

September 26, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIRG17may042

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Hepatitis B

Clinical Trials on Continue nucleos(t)ide analogue

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Papua New Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe