Clinical trial NCT06504485: Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Outcomes and Response to Bulevirtide Treatment
Official title: Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Association With Disease Outcomes and Response to Bulevirtide Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatitis D
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: University of Milan
name: Parma University Hospital
name: University of Rome Tor Vergata
First posted: 2024-07-16
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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).


Eligibility criteria: Inclusion Criteria:

* 18 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide
timeFrame: through study completion, an average of 2 year
measure: 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)
timeFrame: Month 12
Secondary outcomes:
measure: Correlate HDV-specific T cell response with stage of liver disease
timeFrame: through study completion, an average of 2 year
measure: Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting the stage of liver disease
timeFrame: through study completion, an average of 2 year
measure: Correlate the quantification of HDV RNA within exosomes with the stage of liver disease
timeFrame: through study completion, an average of 2 year
measure: Investigate the correlation between the genetic heritage of HDV and the stage of liver disease
timeFrame: through study completion, an average of 2 year
measure: Define the transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection
timeFrame: through study completion, an average of 2 year
measure: Understanding the role of virus mutations in the virus's ability to escape CD8 T cell surveillance
timeFrame: through study completion, an average of 2 year
measure: Correlate the prevalence of HDV-specific T cell responses with response to treatment over time
timeFrame: Month 6
measure: Correlate the prevalence of HDV-specific T cell responses with response to treatment over time
timeFrame: Month 18
measure: Correlate the prevalence of HDV-specific T cell responses with response to treatment over time
timeFrame: through study completion, an average of 2 year
measure: Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting response to treatment with Bulevirtide;
timeFrame: through study completion, an average of 2 year
measure: Correlate quantification of HDV RNA within exosomes with response to Bulevirtide treatment
timeFrame: through study completion, an average of 2 year
measure: Investigate the correlation between the genetic heritage of HDV and the response to treatment with Bulevirtide
timeFrame: through study completion, an average of 2 year
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
Study officials:
References: