- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04102176
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
- Name: Chris Lee, BSc
- Phone Number: (65)67726123
- Email: mdclywc@nus.edu.sg
Study Locations
-
-
-
Singapore, Singapore, 119228
- Recruiting
- National University Hospital
-
Contact:
- Chris Lee, BSc
- Phone Number: 67726123
- Email: mdclywc@nus.edu.sg
-
-
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
|
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)
|
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
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
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Physiological Effects of Drugs
- Protective Agents
- Cariostatic Agents
- Tin Fluorides
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.
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