Compensated Liver Disease (Disorder)BUL-STOPNCT06603311
Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection
A study testing Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection in people with Compensated Liver Disease (Disorder) and Hepatitis D, Chronic, run by Hannover Medical School at 5 sites in 2 countries.
Trial summary
Finding biomarkers for stopping bulevirtide treatment of patients with hepatitis delta Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Compensated Liver Disease (Disorder), Hepatitis D, Chronic
- What is being tested?
- Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 30 Sep 2024to 30 Jun 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men, women, inter/diverse* aged ≥ 18 years
- Signed written informed consent from subject
- Chronic hepatitis delta
- Stable and continued NUC treatment of the underlying HBV infection
- Previous interferon treatment must have stopped at least 6 months before the start of BLV monotherapy
- Previous immunosuppressant therapy must have stopped at least 6 months before the start of BLV therapy
Show all 9Show fewer
- BLV treatment for at least 48 weeks
- HDV-RNA below 100 IU/ml under BLV treatment for at least 24 weeks. Patients should have had at least 2 tests with HDV-RNA below 100 IU/ml plus one test with HDV-RNA below 100 IU/ml+ at screening.
- ALT level below 1.5 fold ULN
Who cannot join
- Patients with decompensated liver cirrhosis (transient mild deviations in liver function parameters are acceptable at the discretion of the investigator) or history of decompensated liver cirrhosis (patients with minimal perihepatic ascites could be included at the discretion of the investigator)
- Hepatocellular carcinoma (HCC)
- Thrombocytopenia (platelet count below 90.000/µl)
- Participation in another interventional clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
- Any additional medical reason not to stop BLV
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Germany4 sites
Charité - University Hospital Berlin (Campus Virchow-Clinic); Department of Hepatology and Gastroenterology
Berlin, State of Berlin, 13353
University Hospital Frankfurt; Medical Clinic 1
Frankfurt am Main, Hesse, 60590
Hannover Medical School; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology
Hanover, Lower Saxony, 30625
University Hospital Heidelberg; Department of Internal Medicine IV: Gastroenterology, Hepatology, Infectious Diseases, Poisoning
Heidelberg, Baden-Wurttemberg, 69120
Italy1 site
Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico; Division of Gastroenterology and Hepatology
Milan, 20122
About this study
Finding biomarkers for stopping bulevirtide treatment of patients with hepatitis delta
Read the detailed description
This is a multicenter, prospective, single-arm, discontinuation study in which patients who have been treated with BLV for at least 48 weeks, are intentionally discontinued from the treatment.
Currently, the treatment duration has not yet been defined and BLV can be given as long as a clinical benefit; is evident. In patients with advanced liver disease, maintenance treatment is recommended by most experts.
In pivotal phase II studies in which patients were treated with BLV for 24-48 weeks, some patients (10-20%) maintained a reduced HDV viral load with normal liver enzymes after the end of treatment (Wedemeyer et al., 2018, 2019, 2020). However, it is completely unclear which patients are able to control HDV infection without antiviral therapies. Biomarkers would be needed to identify patients in whom treatment can stopped safely. This is even more important because HDV flares can be life-threatening in the event of a relapse after stopping BLV. Thus, the main aim of this study is to explore biomarkers in blood and liver associated with maintained virological control after at least 24 weeks of HDV-RNA levels below 100 IU/ml, with at least 2 tests plus one test at screening, on BLV treatment. The investigators hypothesize that biomarker-based criteria should be able to identify patients with a sustained immune control. This information would be highly relevant to personalize treatment duration (or stopping) of BLV treatment, could reduce long-term disease burden, would enable safer treatments and also reduce treatment costs. Within the proposed systematic, unbiased study the investigators follow a broad screening for biomarkers that may be suitable to discriminate in a first step between patients that will experience a virological relapse (HDV RNA above 1000 IU/ml) after discontinuation of treatment and those without.
The investigators plan to include 20 patients in this study. These patients have to have received BLV treatment for at least 48 weeks and have to show HDV-RNA levels below 100 IU/ml in two repeated tests plus one test at screening, for at least 24 weeks while still being on treatment. Treatment will be stopped with the beginning of the study and patients will be followed for 48 weeks. It is expected that up to 14 patients will maintain HDV-RNA control (HDV-RNA below 1000 IU/ml). The other patients are expected to experience a virological relapse. Treating physicians should consider to re-initiate BLV at HDV-RNA levels of above 1000 IU/ml.
The aim of the study is to identify biomarkers that are associated with maintained virological response and could therefore be further investigated as predictive markers for treatment response.
- Being tested
- Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection
- Keywords
- Bulevirtide, HDV, Biomarkers, compensated liver disease
- Medical subject headings
- Hepatitis D, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infectionOther
Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection who have been treated for at least 48 weeks and reached HDV RNA below 100 IU/ml for at least 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Adults with compensated liver disease and HDV with prior Bulevirtide treatment | Experimental | Adults with compensated liver disease who have been treated for chronic HDV infection with bulevirtide (BLV) for at least 48 weeks and reached HDV RNA below 100 IU/ml for at least 24 weeks will finite their BLV treatment. Patients will be followed up for 48 weeks to identify promising biomarkers associated with HDV control after stopping BLV and to evaluate the safety of the novel concept of finite BLV treatment in this group of patients Receives: Other: Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve (AUC) of biomarker on HDV-RNA relapse at week 48
All primary analysis will be carried out in the FAS. All patients will be categorized into two subgroups based on HDV-RNA relapse (yes/no) at week 48:
- HDV-RNA relapse: HDV-RNA ≥ 1000 IU/ml at any time point up to week 48
- No HDV-RNA relapse: HDV-RNA above 1000 IU/ml at all time points up to week 48 For the primary analysis, patients with missing HDV-RNA relapse outcome will be imputed with HDV-RNA relapse. Patients who re-initiated bulevirtide will be analysed as having a HDV-RNA relapse independent of their actual relapse status.
Measured: week 48
Secondary outcomes (6)
Re-initiation of Bulevirtide (BLV)
Number of patients who had to re-initiate treatment (all-cause)
Measured: week 48
Change in QoL
Change in QoL between screening and end-of-study, as assessed by questionnaires
Measured: week 48
Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 48
Number of patients with ALT values below 1.5 ULN at week 48 post treatment stop.
Measured: week 48
Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 24
Number of patients with ALT values below 1.5 ULN at week 24 post treatment stop.
Measured: week 24
HDV-RNA below 100 IU/ml at week 48
Number of patients with HDV-RNA below 100 IU/ml at week 48 after the stop of BLV treatment
Measured: week 48
HDV-RNA below 100 IU/ml at week 24
Number of patients with HDV-RNA below 100 IU/ml at week 24 after the stop of BLV treatment
Measured: week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start30 Sep 2024
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Compensated Liver Disease (Disorder)Studies 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- After discontinuation of the standard treatment of patients with compensated liver disease and chronic hepatitis delta in subjects who received BLV for at least 48 weeks at the discretion of their treating physicians and have reached HDV RNA below 100 IU/ml for at least 24 weeks patients will followed-up for 48 weeks to identify the diagnostic value of biomarkers associated with HDV RNA relapse after stopping BLV and to evaluate the concept of finite BLV treatment.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- German Liver Foundation (DLS), HepNet Study House, German Liverfoundation
- Responsible party
- Principal investigator, Wedemeyer, Hans Heinrich Prof. Dr., Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06603311
- Sponsor's protocol ID
- BUL-STOP
- Acronym
- BUL-STOP
- Status last verified
- Feb 2026
- First submitted
- 16 Sep 2024
- Last updated
- 3 Mar 2026
- 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 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection
- ClinicalTrials.gov ID
- NCT06603311
- Acronym / sponsor ID
- BUL-STOP / BUL-STOP
- Keywords
- Bulevirtide, HDV, Biomarkers, compensated liver disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Collaborators
- German Liver Foundation (DLS), HepNet Study House, German Liverfoundation
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 19 Sep 2024 (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.
Finding biomarkers for stopping bulevirtide treatment of patients with hepatitis delta
Detailed description
This is a multicenter, prospective, single-arm, discontinuation study in which patients who have been treated with BLV for at least 48 weeks, are intentionally discontinued from the treatment.
Currently, the treatment duration has not yet been defined and BLV can be given as long as a clinical benefit; is evident. In patients with advanced liver disease, maintenance treatment is recommended by most experts.
In pivotal phase II studies in which patients were treated with BLV for 24-48 weeks, some patients (10-20%) maintained a reduced HDV viral load with normal liver enzymes after the end of treatment (Wedemeyer et al., 2018, 2019, 2020). However, it is completely unclear which patients are able to control HDV infection without antiviral therapies. Biomarkers would be needed to identify patients in whom treatment can stopped safely. This is even more important because HDV flares can be life-threatening in the event of a relapse after stopping BLV. Thus, the main aim of this study is to explore biomarkers in blood and liver associated with maintained virological control after at least 24 weeks of HDV-RNA levels below 100 IU/ml, with at least 2 tests plus one test at screening, on BLV treatment. The investigators hypothesize that biomarker-based criteria should be able to identify patients with a sustained immune control. This information would be highly relevant to personalize treatment duration (or stopping) of BLV treatment, could reduce long-term disease burden, would enable safer treatments and also reduce treatment costs. Within the proposed systematic, unbiased study the investigators follow a broad screening for biomarkers that may be suitable to discriminate in a first step between patients that will experience a virological relapse (HDV RNA above 1000 IU/ml) after discontinuation of treatment and those without.
The investigators plan to include 20 patients in this study. These patients have to have received BLV treatment for at least 48 weeks and have to show HDV-RNA levels below 100 IU/ml in two repeated tests plus one test at screening, for at least 24 weeks while still being on treatment. Treatment will be stopped with the beginning of the study and patients will be followed for 48 weeks. It is expected that up to 14 patients will maintain HDV-RNA control (HDV-RNA below 1000 IU/ml). The other patients are expected to experience a virological relapse. Treating physicians should consider to re-initiate BLV at HDV-RNA levels of above 1000 IU/ml.
The aim of the study is to identify biomarkers that are associated with maintained virological response and could therefore be further investigated as predictive markers for treatment response.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- After discontinuation of the standard treatment of patients with compensated liver disease and chronic hepatitis delta in subjects who received BLV for at least 48 weeks at the discretion of their treating physicians and have reached HDV RNA below 100 IU/ml for at least 24 weeks patients will followed-up for 48 weeks to identify the diagnostic value of biomarkers associated with HDV RNA relapse after stopping BLV and to evaluate the concept of finite BLV treatment.
| Arm | Type | Receives |
|---|---|---|
| Adults with compensated liver disease and HDV with prior Bulevirtide treatment | Experimental | Other: Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infectionAdults with compensated liver disease who have been treated for chronic HDV infection with bulevirtide (BLV) for at least 48 weeks and reached HDV RNA below 100 IU/ml for at least 24 weeks will finite their BLV treatment. Patients will be followed up for 48 weeks to identify promising biomarkers associated with HDV control after stopping BLV and to evaluate the safety of the novel concept of finite BLV treatment in this group of patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men, women, inter/diverse* aged ≥ 18 years
- Signed written informed consent from subject
- Chronic hepatitis delta
- Stable and continued NUC treatment of the underlying HBV infection
- Previous interferon treatment must have stopped at least 6 months before the start of BLV monotherapy
Key exclusion criteria (5 listed)
- Patients with decompensated liver cirrhosis (transient mild deviations in liver function parameters are acceptable at the discretion of the investigator) or history of decompensated liver cirrhosis (patients with minimal perihepatic ascites could be included at the discretion of the investigator)
- Hepatocellular carcinoma (HCC)
- Thrombocytopenia (platelet count below 90.000/µl)
- Participation in another interventional clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
- Any additional medical reason not to stop BLV
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 |
|---|---|---|
| Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infectionStop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection who have been treated for at least 48 weeks and reached HDV RNA below 100 IU/ml for at least 24 weeks. | Other | Adults with compensated liver disease and HDV with prior Bulevirtide treatment |
Primary outcome
Area under the curve (AUC) of biomarker on HDV-RNA relapse at week 48
Time frame: week 48
All primary analysis will be carried out in the FAS. All patients will be categorized into two subgroups based on HDV-RNA relapse (yes/no) at week 48: 1. HDV-RNA relapse: HDV-RNA ≥ 1000 IU/ml at any time point up to week 48 2. No HDV-RNA relapse: HDV-RNA above 1000 IU/ml at all time points up to week 48 For the primary analysis, patients with missing HDV-RNA relapse outcome will be imputed with HDV-RNA relapse. Patients who re-initiated bulevirtide will be analysed as having a HDV-RNA relapse independent of their actual relapse status.
6 secondary outcomes
Re-initiation of Bulevirtide (BLV)
Time frame: week 48
Change in QoL
Time frame: week 48
Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 48
Time frame: week 48
Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 24
Time frame: week 24
HDV-RNA below 100 IU/ml at week 48
Time frame: week 48
HDV-RNA below 100 IU/ml at week 24
Time frame: week 24
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 3 Mar 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection in people with Compensated Liver Disease (Disorder) and Hepatitis D, Chronic, run by Hannover Medical School at 5 sites in 2 countries.
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 9 inclusion and 5 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 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, Italy. 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?
Area under the curve (AUC) of biomarker on HDV-RNA relapse at week 48 (time frame: week 48). 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 3 Mar 2026.