Effectiveness and Safety of Bulevirtide (BLV) Therapy in Patients With Chronic Hepatitis Delta (CHD) in Italy (D-SHIELD) (D-SHIELD)

Effectiveness and Safety of Bulevirtide (BLV) Therapy in Patients With Chronic Hepatitis Delta (CHD) in Italy: a Multicenter Prospective Real Life Data Study

Multicenter pharmacological observational prospective, no-profit, study.

This study was designed to get a "real-life" snapshot across several Italian Hepatology centers. All HDV patients are followed up according to EASL 2017 guidelines. This allows uniformity on the indication for antiviral treatment and management of that antiviral therapy. No off-label medications are used. All data are retrievable from the patient's medical record. In addition, clinical and biochemical data from patients at month 0, 1, 2, 4, 6 and 12 of treatment, and otherwise within the study period, will be collected longitudinally.

The primary objective of the study is to describe the virological response to BLV in all patients starting BLV therapy for CHD, defined as a >2 Log decline in HDV-RNA or undetectable HDV-RNA (using the Robogene 2.0 quantitative kit, LLQ <6 IU/ml) at month 12 of therapy.

HDV patients who will start therapy with BLV 2 mg/day from May 2023, according to AIFA guidelines, will be consecutively enrolled.

Study Overview

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

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milan, MI, 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

All patients with CHD (quantifiable HDV-RNA) who will start treatment with 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 met the inclusion criteria and none of the exclusion criteria.

Description

Inclusion Criteria:

• 18 years of age or older
• Chronic hepatitis delta
• Compensated cirrhosis HDV related
• Patients who will start therapy with BLV 2 mg/day from May 2023

Exclusion Criteria:

• HDV-related decompensated cirrhosis (CPT ≥7)

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the virological response to BLV in all patients starting BLV therapy for CHD	Percentage of patients with undetectable HDV RNA	Month 6
Describe the virological response to BLV in all patients starting BLV therapy for CHD	Percentage of patients with ≥ 2 log IU/ml decline of HDV RNA	Month 12

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	Proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA	Month 6
Evaluation of the proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA	Proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA	Month 12
Evaluation of the proportion of patients with virological response, defined as undetectable HDV-RNA	Proportion of patients with virological response, defined as undetectable HDV-RNA	Month 6
Evaluation of the proportion of patients with virological response, defined as undetectable HDV-RNA	Proportion of patients with virological response, defined as undetectable HDV-RNA	Month 12
Evaluation of the percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT	Percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT	Month 6
Evaluation of the percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT	Percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT	Month 12
Evaluation of the percentage of patients with normal ALT	Percentage of patients with normal ALT	Month 6
Evaluation of the percentage of patients with normal ALT	Percentage of patients with normal ALT	Month 12
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	Percentage of patients who remain free of liver complications (de novo HCC or onset of decompensation)	Month 6
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	Percentage of patients who remain free of liver complications (de novo HCC or onset of decompensation)	Month 12
Investigation of changes over time in serum levels of HBsAg (UI/mL)	Change in serum levels of HBsAg- by medians and ranges	Month 6
Investigation of changes over time in serum levels of HBsAg (UI/mL)	Change in serum levels of HBsAg- by medians and ranges	Month 12
Investigation of changes over time in serum levels of albumin (g/dL)	Change in serum levels albumin- by medians and ranges	Month 6
Investigation of changes over time in serum levels of albumin (g/dL)	Change in serum levels albumin- by medians and ranges	Month 12
Investigation of changes over time in serum levels of platelets (10e9/L)	Change in serum levels of platelets - by medians and ranges	Month 6
Investigation of changes over time in serum levels of platelets (10e9/L)	Change in serum levels of platelets - by medians and ranges	Month 12
Investigation of changes over time in serum levels of AFP (µg/L)	Change in serum levels of AFP - by medians and ranges	Month 6
Investigation of changes over time in serum levels of AFP (µg/L)	Change in serum levels of AFP - by medians and ranges	Month 12
Evaluation of treatment safety	Occurrence of change in serum bile acid levels (µmol/L)	Month 6
Evaluation of treatment safety	Occurrence of adverse events	Month 6
Evaluation of treatment safety	Occurrence of change in serum bile acid levels (µmol/L)	Month 12
Evaluation of treatment safety	Occurrence of adverse events	Month 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Actual): November 1, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis A; Hepatitis; Hepatitis D
• Other Study ID Numbers: 184853

Drug and device information, study documents

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