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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Bulevirtide
  dose of 2 mg/day subcutaneously

Первичные конечные точки

• Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide [Срок оценки: 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) [Срок оценки: Month 12]

Вторичные конечные точки (12)

• Correlate HDV-specific T cell response with stage of liver disease [Срок оценки: 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 [Срок оценки: through study completion, an average of 2 year]
• Correlate the quantification of HDV RNA within exosomes with the stage of liver disease [Срок оценки: through study completion, an average of 2 year]
• Investigate the correlation between the genetic heritage of HDV and the stage of liver disease [Срок оценки: 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 [Срок оценки: through study completion, an average of 2 year]
• Understanding the role of virus mutations in the virus's ability to escape CD8 T cell surveillance [Срок оценки: through study completion, an average of 2 year]
• Correlate the prevalence of HDV-specific T cell responses with response to treatment over time [Срок оценки: Month 6]
• Correlate the prevalence of HDV-specific T cell responses with response to treatment over time [Срок оценки: Month 18]
• Correlate the prevalence of HDV-specific T cell responses with response to treatment over time [Срок оценки: through study completion, an average of 2 year]
• Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting response to treatment with Bulevirtide; [Срок оценки: through study completion, an average of 2 year]
• Correlate quantification of HDV RNA within exosomes with response to Bulevirtide treatment [Срок оценки: through study completion, an average of 2 year]
• Investigate the correlation between the genetic heritage of HDV and the response to treatment with Bulevirtide [Срок оценки: through study completion, an average of 2 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology an — Milan

Идентификаторы

NCT: NCT06504485 · P2022WEXP2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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