Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Outcomes and Response to Bulevirtide Treatment

NCT06504485 | Recruiting

• 1 other identifier: P2022WEXP2
• Study Type: observational
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

Pharmacological, single-center, non-profit observational study. The present study is part of a cooperation project between the SC Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy), the University of Milan, the University of Parma and Rome Tor Vergata, funded under the call for Research Projects of Significant National Interest - 2022 PNRR Call (Prot. P2022WEXP2). Hepatitis D virus (HDV) is a defective RNA virus, which requires the presence of hepatitis B virus (HBV) to infect liver cells and propagate. To date, the mechanisms underlying the accelerated disease progression in the natural history of Delta hepatitis are poorly understood, as is the course of the HDV-specific immune response (CD4 and CD8 T cells). As in chronic HBV and HCV infections, the outcome of chronic HDV infection appears to be dictated primarily by the host immune response, which represents a key determinant for virus control or persistence. For HBV/HDV coinfection, the role of T cells has not been well defined, as suitable animal models are lacking and so far few HDV-specific T cell epitopes have been precisely mapped, mainly limited to HLA-B alleles. The study is divided into two substudies (cross-sectional and longitudinal). The primary objective of the cross-sectional study is to calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide. The primary objective of the longitudinal study is the change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment).

Conditions

Hepatitis D

Outcome Measures

Primary Outcomes (2)

• Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide

  Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide

  through study completion, an average of 2 year

• Change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment)

  Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection after 12 months of treatment with Bulevirtide compared to baseline (pre-therapy)

  Month 12

Secondary Outcomes (12)

• Correlate HDV-specific T cell response with stage of liver disease

  through study completion, an average of 2 year

• Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting the stage of liver disease

  through study completion, an average of 2 year

• Correlate the quantification of HDV RNA within exosomes with the stage of liver disease

  through study completion, an average of 2 year

• Investigate the correlation between the genetic heritage of HDV and the stage of liver disease

  through study completion, an average of 2 year

• Define the transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection

  through study completion, an average of 2 year

Study Arms (2)

Hepatis Delta naive

Patients with HDV infection naïve to Bulevirtide therapy

Hepatis Delta in therapy

Patients with HDV cirrhosis consecutively started on Bulevirtide therapy during the study enrollment period

Drug: Bulevirtide

Interventions

Bulevirtide DRUG

dose of 2 mg/day subcutaneously

Hepatis Delta in therapy

Eligibility Criteria

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

Study Population

The study will enroll patients co-infected with HBV-HDV (defined by positivity of HDV RNA for at least 6 months) who meet the inclusion criteria and no exclusion criteria

You may qualify if:

• years of age or older
• Ability to understand and sign the informed consent
• Chronic HDV infection defined by positivity of HBsAg antigen (HBV) and HDV RNA (HBV-HDV co-infection) for at least 6 months at the time of enrollment.

You may not qualify if:

• Co-infection with other viruses (HCV, HIV)
• Treatment with immunosuppressive/immunomodulatory drugs
• Other congenital and/or acquired immunodeficiency conditions

Sponsors & Collaborators

• University of Milan: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Parma University Hospital: collaborator
• University of Rome Tor Vergata: collaborator

Study Sites (1)

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

Milan, 20122, Italy

RECRUITING

MeSH Terms

Conditions

Hepatitis D

Interventions

bulevirtide

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Central Study Contacts

Pietro Lampertico, MD

CONTACT

0255035432; pietro.lampertico@unimi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 16, 2024
• Study Start: September 1, 2024
• Primary Completion: November 30, 2025
• Study Completion: February 28, 2026
• Last Updated: January 15, 2026

Record last verified: 2025-12

Locations

IT (1)