Clinical trial NCT06603311: Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection
Official title: Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Compensated Liver Disease (Disorder)
Hepatitis D, Chronic
Keywords: Bulevirtide
HDV
Biomarkers
compensated liver disease
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: German Liver Foundation (DLS)
name: HepNet Study House, German Liverfoundation
First posted: 2024-09-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Men, women, inter/diverse\* aged ≥ 18 years
2. Signed written informed consent from subject
3. Chronic hepatitis delta
4. Stable and continued NUC treatment of the underlying HBV infection
5. Previous interferon treatment must have stopped at least 6 months before the start of BLV monotherapy
6. Previous immunosuppressant therapy must have stopped at least 6 months before the start of BLV therapy
7. BLV treatment for at least 48 weeks
8. 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.
9. ALT level below 1.5 fold ULN

Exclusion Criteria:

1. 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)
2. Hepatocellular carcinoma (HCC)
3. Thrombocytopenia (platelet count below 90.000/µl)
4. Participation in another interventional clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
5. Any additional medical reason not to stop BLV

Primary outcomes:
measure: Area under the curve (AUC) of biomarker on HDV-RNA relapse at week 48
timeFrame: week 48
Secondary outcomes:
measure: Re-initiation of Bulevirtide (BLV)
timeFrame: week 48
measure: Change in QoL
timeFrame: week 48
measure: Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 48
timeFrame: week 48
measure: Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 24
timeFrame: week 24
measure: HDV-RNA below 100 IU/ml at week 48
timeFrame: week 48
measure: HDV-RNA below 100 IU/ml at week 24
timeFrame: week 24
Other outcomes:
measure: Liver-related Events
timeFrame: week 48
measure: Alanine transaminase (ALT) flares
timeFrame: week 48
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg; Department of Internal Medicine IV: Gastroenterology, Hepatology, Infectious Diseases, Poisoning
state: Baden Württemberg
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt; Medical Clinic 1
state: Hesse
city: Hannover
country: Germany
facility: Hannover Medical School; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology
state: Lower Saxony
city: Berlin
country: Germany
facility: Charité - University Hospital Berlin (Campus Virchow-Clinic); Department of Hepatology and Gastroenterology
city: Milan
country: Italy
facility: Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico; Division of Gastroenterology and Hepatology
Study officials:
References: