Chronic Hepatitis BHALT-NUCSNCT04102176
Halting Nucleoside Analogues in Chronic Hepatitis B
A study testing stopping nucleos(t)ide therapy and Continue nucleos(t)ide analogue in people with Chronic Hepatitis B, run by Seng Gee Lim at 1 site in Singapore.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- stopping nucleos(t)ide therapy and Continue nucleos(t)ide analogue
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSingapore
- Study dates
- 29 Jan 2019to Feb 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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
Who cannot join
- • 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Hepatitis B
- Being tested
- stopping nucleos(t)ide therapy, Continue nucleos(t)ide analogue
- Keywords
- chronic hepatitis B, nucleoside analogues, stopping, discontinuing
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stopping nucleos(t)ide therapyOther
patients taking nucleoside(t)ide therapy will stop treatment
Continue nucleos(t)ide analogueOther
Continue nucleos(t)ide analogue
| Study group | Role | What they receive |
|---|---|---|
| Continue nucleos(t)ide analogue | Active comparator | patients will be given open label tenofovir alafenamide Receives: 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) Receives: Other: stopping nucleos(t)ide therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBsAg loss
Absence of HBsAg by ELISA
Measured: Through year 3
Secondary outcomes (3)
Hepatitis B flare
increase in ALT associated with increase in HBV DNA
Measured: Through year 3
virological relapse
increase in HBV DNA without increase in ALT
Measured: Through year 3
Restarting antiviral therapy
Those who have to start therapy based on clinical indications after stopping therapy
Measured: Through year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start29 Jan 2019
- Primary completionFeb 2026 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel arm study randomised 1:2
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seng Gee Lim
- Sponsor type
- University, hospital or other
- Collaborators
- Tan Tock Seng Hospital, Singapore General Hospital, Changi General Hospital
- Responsible party
- Sponsor-investigator, Seng Gee Lim, National University Health System, Singapore
- Investigators
- Seng Gee Lim, MBBS MD, Principal investigator, National University Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04102176
- Sponsor's protocol ID
- CIRG17may042
- Acronym
- HALT-NUCS
- Status last verified
- Jul 2025
- First submitted
- 27 May 2019
- Last updated
- 14 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HALT NUCs: Halting Nucleoside Analogue Therapy in Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT04102176
- Acronym / sponsor ID
- HALT-NUCS / CIRG17may042
- Conditions
- Chronic Hepatitis B
- Keywords
- chronic hepatitis B, nucleoside analogues, stopping, discontinuing
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Seng Gee LimUniversity, hospital or other
- Collaborators
- Tan Tock Seng Hospital, Singapore General Hospital, Changi General Hospital
- Study start
- 29 Jan 2019 (actual)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel arm study randomised 1:2
| Arm | Type | Receives |
|---|---|---|
| Continue nucleos(t)ide analogue | Active comparator | Other: Continue nucleos(t)ide analoguepatients will be given open label tenofovir alafenamide |
| Stopping nucleos(t)ide analogue | Experimental | Other: stopping nucleos(t)ide therapypatients will stop nucleos(t)ide therapy (such as entecavir, tenofovir, lamivudine or adefovir) |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- • Between 21 and 75 years old.
Key exclusion criteria (10 listed)
- • 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stopping nucleos(t)ide therapypatients taking nucleoside(t)ide therapy will stop treatment | Other | Stopping nucleos(t)ide analogue |
| Continue nucleos(t)ide analogueContinue nucleos(t)ide analogue | Other | Continue nucleos(t)ide analogue |
Primary outcome
HBsAg loss
Time frame: Through year 3
Absence of HBsAg by ELISA
3 secondary outcomes
Hepatitis B flare
Time frame: Through year 3
virological relapse
Time frame: Through year 3
Restarting antiviral therapy
Time frame: Through year 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seng Gee Lim, MBBS MD principal investigator
National University Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing stopping nucleos(t)ide therapy and Continue nucleos(t)ide analogue in people with Chronic Hepatitis B, run by Seng Gee Lim at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBsAg loss (time frame: Through year 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.