Finite Treatment of Hepatitis Delta With Bulevirtide: Identification of Biomarkers Associated With Sustained Control of HDV Infection

NCT06603311 | Active Not Recruiting DMC

• 1 other identifier: BUL-STOP
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 5

Brief Summary

Finding biomarkers for stopping bulevirtide treatment of patients with hepatitis delta

Conditions

Compensated Liver Disease (Disorder); Hepatitis D, Chronic

Keywords

Bulevirtide; HDV; Biomarkers; compensated liver disease

Outcome Measures

Primary Outcomes (1)

• 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: 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.

  week 48

Secondary Outcomes (6)

• Re-initiation of Bulevirtide (BLV)

  week 48

• Change in QoL

  week 48

• Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 48

  week 48

• Alanine transaminase (ALT) values below 1.5x the upper limit of normal (ULN) at week 24

  week 24

• HDV-RNA below 100 IU/ml at week 48

  week 48

Other Outcomes (2)

• Liver-related Events

  week 48

• Alanine transaminase (ALT) flares

  week 48

Study Arms (1)

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

Other: Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection

Interventions

Stop Treatment with Bulevertide in patients with compensated liver disease and chronic HDV infection OTHER

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.

Adults with compensated liver disease and HDV with prior Bulevirtide treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HepNet Study House, German Liverfoundation: collaborator
• Hannover Medical School: lead
• German Liver Foundation (DLS): collaborator

Study Sites (5)

University Hospital Heidelberg; Department of Internal Medicine IV: Gastroenterology, Hepatology, Infectious Diseases, Poisoning

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Hospital Frankfurt; Medical Clinic 1

Frankfurt am Main, Hesse, 60590, Germany

Location

Hannover Medical School; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology

Hanover, Lower Saxony, 30625, Germany

Location

Charité - University Hospital Berlin (Campus Virchow-Clinic); Department of Hepatology and Gastroenterology

Berlin, State of Berlin, 13353, Germany

Location

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico; Division of Gastroenterology and Hepatology

Milan, 20122, Italy

Location

MeSH Terms

Conditions

Hepatitis D, Chronic

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Heiner Wedemeyer

Model Details: 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.

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DE (4)