10119473 -VIROMARKERS HDV Biomarkers Study

NCT07313358 | Not Yet Recruiting

• 1 other identifier: 101194735-HDV
• Study Type: observational
• Target: 220
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an observational study, in which clinical data, samples, and any other procedures possibly already performed on participants, were performed within the scope of clinical practice or within the scope of otherwise authorized projects, and that therefore there are no procedures performed specifically for this study, which instead uses data collected previously or prospectively during an extended follow-up, but in any case within the scope of current clinical practice. Most participants have been enrolled and followed up at the project partners' clinical sites over 2023-2025. Their follow-up and sample collection will continue over the duration of the project. At the time of enrollment, demographics, medical history, medications and treatments prescribed were recorded and will be used in this study if the participant consent to be included also in VIROMARKERS. HDV genotypes/subgenotypes will be determined ex-novo on existing baseline stored samples. The harmonization of HDV-RNA assays by utilizing standardized and validated flowcharts still represents a relevant diagnostic unmet clinical need for the appropriate monitoring of patients with CHD receiving BLV treatment. Furthermore, information on long-term virological response and factors predictive of virological outcome is scarce. Specific primary objectives to characterise the response to bulevirtide in CHD include:

• To estimate the percentage of participants who will achieve virological response (defined as a decline in serum HDV RNA of \>2 log or to undetectable HDV-RNA) and the proportion achieving undetectable HDV-RNA at week 48, 96 and 144 weeks of BLV treatment.
• To estimate the percentage of participants who will achieve biochemical response and combined response (defined as achievement of virological response and ALT normalization) at week 48, 96 and 144 weeks of BLV treatment.
• To evaluate whether HDV-RNA levels at baseline or their kinetics during the first 12 weeks of BLV treatment can predict the achievement of undetectable serum HDV-RNA during BLV treatment.

Conditions

HDV Infection

Keywords

HDV infection; bulevirtide; biomarkers

Outcome Measures

Primary Outcomes (1)

• HDV Viral Load

  HDV-RNA decline \> 2 log OR reaching undetectable HDV-RNA

  48, 96, 144 weeks after starting Bulevirtide

Study Arms (1)

HDV-BLV

patients with HDV infection who initiated BLV from January 2023 to February 2025 for whom retrospective data and samples are available. Follow-up and sample collection will be extended for this population over the period of the study grant. To be eligible for inclusion in both the retrospective and prospective part of the study, participants have to be ≥18 years of age, have signed an informed consent and satisfy the following additional criteria: A diagnosis of chronic HDV infection with or without compensated cirrhosis Having started BLV monotherapy 2mg/day according to the criteria reported in the recent clinical practice guidelines on HDV infection promoted by EASL \[EASL CPG 2024\] Be under effective treatment with nucleoside analogues with HBV-DNA \<20 IU/ml at the time of starting BLV

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

participants have to be ≥18 years of age, have signed an informed consent and satisfy the following additional criteria: A diagnosis of chronic HDV infection with or without compensated cirrhosis Having started BLV monotherapy 2mg/day according to the criteria reported in the recent clinical practice guidelines on HDV infection promoted by EASL \[EASL CPG 2024\] Be under effective treatment with nucleoside analogues with HBV-DNA \<20 IU/ml at the time of starting BLV

You may qualify if:

• Be \> 18 years of age
• Sign an informed consent
• Have a diagnosis of HDV infection with or without compensated cirrhosis
• Having started BLV monotherapy 2mg/day according to the criteria reported in the recent clinical practice guidelines on HDV infection promoted by EASL (EASL CPG 2023)
• Be under effective treatment with nucleoside analogues with HBV-DNA \<20 IU/ml at the time of starting BLV

You may not qualify if:

• Decompensated liver disease
• BLV combined with pegIFN
• Past treatment with BLV

Sponsors & Collaborators

• Euresist Network GEIE: collaborator
• Informapro Srl: collaborator
• Royal Free and University College Medical School: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• EUROPEAN LIVER PATIENTS ASSOCIATION: collaborator
• University of Rome Tor Vergata: lead

Study Sites (2)

Heinrich Heine University

Düsseldorf, Germany, 40225, Germany

Location

Università di Milano

Milan, Italy, 20122, Italy

Location

Related Publications (7)

• Rodgers MA, Shah PA, Anderson M, Vallari AS, Gersch J, Mbanya D, Sauleda Oliveras S, Choudhry S, Leary TP, Kuhns MC, Dawson GJ, Cloherty GA, Lau DTY. Characterization of HBV surface antigen isoforms in the natural history and treatment of HBV infection. Hepatol Commun. 2023 Apr 4;7(4):e0027. doi: 10.1097/HC9.0000000000000027. eCollection 2023 Apr 1.

  PMID: 37026760 BACKGROUND

• Charre C, Regue H, Deny P, Josset L, Chemin I, Zoulim F, Scholtes C. Improved hepatitis delta virus genome characterization by single molecule full-length genome sequencing combined with VIRiONT pipeline. J Med Virol. 2023 Mar;95(3):e28634. doi: 10.1002/jmv.28634.

  PMID: 36879535 BACKGROUND

• Pfefferkorn M, Bohm S, Schott T, Deichsel D, Bremer CM, Schroder K, Gerlich WH, Glebe D, Berg T, van Bommel F. Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers. Gut. 2018 Nov;67(11):2045-2053. doi: 10.1136/gutjnl-2017-313811. Epub 2017 Sep 26.

  PMID: 28951526 BACKGROUND

• Wedemeyer H, Aleman S, Brunetto MR, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Manuilov D, Suri V, An Q, Da B, Flaherty J, Osinusi A, Liu Y, Merle U, Schulze Zur Wiesch J, Zeuzem S, Ciesek S, Cornberg M, Lampertico P; MYR 301 Study Group. A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D. N Engl J Med. 2023 Jul 6;389(1):22-32. doi: 10.1056/NEJMoa2213429. Epub 2023 Jun 22.

  PMID: 37345876 BACKGROUND

• Brancaccio G, Salpini R, Piermatteo L, Surdo M, Fini V, Colagrossi L, Cantone M, Battisti A, Oda Y, Di Carlo D, Ceccherini-Silberstein F, Perno CF, Gaeta GB, Svicher V. An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression. Microorganisms. 2021 Apr 2;9(4):752. doi: 10.3390/microorganisms9040752.

  PMID: 33918474 BACKGROUND

• Stelzl E, Ciesek S, Cornberg M, Maasoumy B, Heim A, Chudy M, Olivero A, Miklau FN, Nickel A, Reinhardt A, Dietzsch M, Kessler HH. Reliable quantification of plasma HDV RNA is of paramount importance for treatment monitoring: A European multicenter study. J Clin Virol. 2021 Sep;142:104932. doi: 10.1016/j.jcv.2021.104932. Epub 2021 Jul 24.

  PMID: 34333392 BACKGROUND

• Degasperi E, Anolli MP, Jachs M, Reiberger T, De Ledinghen V, Metivier S, D'Offizi G, di Maria F, Schramm C, Schmidt H, Zollner C, Tacke F, Dietz-Fricke C, Wedemeyer H, Papatheodoridi M, Papatheodoridis G, Carey I, Agarwal K, Van Bommel F, Brunetto MR, Cardoso M, Verucchi G, Ciancio A, Zoulim F, Aleman S, Semmo N, Mangia A, Hilleret MN, Merle U, Santantonio TA, Coppola N, Pellicelli A, Roche B, Causse X, D'Alteroche L, Dumortier J, Ganne N, Heluwaert F, Ollivier I, Roulot D, Vigano M, Loglio A, Federico A, Pileri F, Maracci M, Tonnini M, Arpurt JP, Barange K, Billaud E, Pol S, Gervais A, Minello A, Rosa I, Puoti M, Lampertico P. Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis. J Hepatol. 2025 Jun;82(6):1012-1022. doi: 10.1016/j.jhep.2024.12.044. Epub 2025 Jan 8.

  PMID: 39793613 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

blood samples for testing of levels of HBsAg isoforms, HDV genotypes/subgenotypes and Altona/Qiagen HDV RNA quantification. The virological status of all participants enrolled will be assessed every 3 months, according to the guidelines promoted by European Association for the Study of the Liver in 2023, at week 48, 96 and 144 after enrollment. The 48-, 96- and 144-week follow-up status assessment will include: HDV RNA levels ALT levels Adverse events Liver-related events Hospitalization, including length of stay The use of stored specimens will be reviewed and approved by the Protocol Team, the VIROMARKERS Scientific Steering Committee, and EC Horizon Europe.

Study Officials

• PIETRO LAMPERTICO, PROFESSOR

  UNIVERSITA' DI MILANO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

VALENTINA SVICHER, PROFESSOR

CONTACT

+39 333 238 1462; valentina.svicher@uniroma2.it

ROMINA SALPINI, RESEARCHER

CONTACT

romina.salpini@uniroma2.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 31, 2025
• Study Start: February 20, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Start date: july 31 2025 end dat: not defined
• Access Criteria: Any researcher can apply for the access to the Project Coordinator

Locations

IT (1); DE (1)