Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis (SAVE-D)

Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis (SAVE-D Study)

Retrospective and prospective, pharmacological, multicentre, non-profit observational study.

Consecutive patients with HDV-related compensated cirrhosis starting Bulevirtide 2 mg/day from September 2019 to December 2025 will be enrolled in the study.

Aim of this study is to investigate virological and clinical effectiveness of Bulevirtide 2 mg/day in patients with HDV-related compensated cirrhosis in the real-life setting.

Primary endpoint of the study is the rate of virological response, defined as at least 2 Log decline or undetectable HDV RNA compared to baseline, at week 96 of treatment.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis D
• Intervention / Treatment: Drug: Bulevirtide

• Study Type: Observational
• Enrollment (Estimated): 266

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20122
    • Recruiting
    • Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
    • Contact: Pietro Lampertico, MD; Phone Number: 0255035432; Email: pietro.lampertico@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study will enrol patients with chronic HDV infection (defined by HDV RNA positivity for at least 6 months) who started or will start BLV 2 mg/day during the study period at the S.C. Gastroenterology and Hepatology (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico) and at participating centers, and who meet the inclusion criteria and do not present any of the exclusion criteria. The decision to treat patients with BLV is determined based on the clinical judgment of the treating physicians prior to study enrolment.

Description

Inclusion Criteria:

• Age≥18 years
• HDV-related compensated cirrhosis defined by positivity of HDV RNA for at least 6 months and clinical or laboratory or histological diagnosis of cirrhosis
• Started treatment with BLV monotherapy between September 1st 2019 and 2025

Exclusion Criteria:

• Chronic hepatitis without any evidence of cirrhosis
• Decompensated cirrhosis
• PegIFN alpha therapy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hepatis Delta; Bulevirtide (BLV) at a dose of 2 mg/day subcutaneously	Drug: Bulevirtide; dose of 2 mg/day subcutaneously; Other Names: Hepcludex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the virological response rate to BLV	Percentage of patients with >2 Log decline in HDV-RNA (IU/mL)	Week 96
Investigate the virological response rate to BLV	Percentage of patients with undetectable HDV-RNA (IU/mL)	Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA (IU/mL) or undetectable HDV-RNA (IU/mL) along with normalization of ALT (combined response)	Percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT (combined response)	Week 96
Evaluation of the percentage of patients with normal ALT	Percentage of patients with normal ALT	Week 96
Evaluation of the percentage of patients with <1 Log decrease in HDV-RNA	Percentage of patients with < 1 log decline HDV RNA levels	Week 96
Evaluation of the percentage of patients with clinical response, i.e., the percentage of patients who remain free of liver complications, such as HCC or decompensation, at week 96 of treatment.	Percentage of patients who remain free of liver complications (de novo HCC or onset of decompensation) at week 96;	Week 96
Evaluation of the correlation between baseline or on-treatment biochemical/clinical variables and virological response	Baseline and on-treatment biochemical and clinical variables predicting virological response to BLV	Week 96
Evaluation of virological and clinical responses from year 2 (week 96) to year 5 only (only if data of this patients is available)	Percentage of patients with virological, biochemical and clinical responses from year 2 (week 96) to year 5	Year 5
Evaluation of bile acids levels over time and correlation of bile levels with virological response rates	Correlation between bile acids levels and virological response over time	Week 96

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 17, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Hepatitis; Hepatitis D
• Other Study ID Numbers: IN-IT-589-7118

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No