Clinical trial • Phase II • Infectious Disease|Rare Disease
TOBEVIBART for Chronic Hepatitis D (HDV) infection
Phase II trial of TOBEVIBART for Chronic Hepatitis D (HDV) infection. Randomised, open-label. 119 participants.
Overview
- Trial Therapeutic Area
- Infectious Disease|Rare Disease
- Trial Disease
- Chronic Hepatitis D (HDV) infection
- Trial Stage
- Phase II
- Drug Modality
- Monoclonal antibody|Oligonucleotide
Key dates
- Initial CTIS Submission Date
- 30-08-2024
- First CTIS Authorization Date
- 16-09-2024
Trial design
Randomised, open-label Phase II trial in Netherlands, France, Germany and others.
- Randomised
- Yes
- Open Label
- Yes
- Target Sample Size
- 119
- Trial Duration For Participant
- 1344
Eligibility
Recruits 119 Vulnerable population flag is selected. The protocol requires participants to be capable of giving signed informed consent. Only adults (Age ≥ 18) are eligible. Specific informed consent forms (ICFs) are provided, including adult ICFs and separate ICFs for pregnant participants/partners and optional substudies; ICFs are available in multiple country/language versions (e.g. Dutch, French, German, Italian, Romanian, Bulgarian, English) as listed in the public documents..
- Pregnancy Exclusion
- Female participants must have a negative pregnancy test or confirmation of postmenopausal status. Postmenopausal status is defined as 12 months with no menses without an alternative medical cause (see Section 10.7 for additional details). Women of childbearing potential (WOCBP) must have a negative blood pregnancy test at screening and a negative urine pregnancy test on Day 1, cannot be breast feeding, and must be willing to use highly effective methods of contraception (Section 10.7) 14 days before study intervention administration through 48 weeks after the last dose of VIR-2218 or VIR-3434. Female participants must also agree to refrain from egg donation and in vitro fertilization from the time of study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434.
- Vulnerable Population
- Vulnerable population flag is selected. The protocol requires participants to be capable of giving signed informed consent. Only adults (Age ≥ 18) are eligible. Specific informed consent forms (ICFs) are provided, including adult ICFs and separate ICFs for pregnant participants/partners and optional substudies; ICFs are available in multiple country/language versions (e.g. Dutch, French, German, Italian, Romanian, Bulgarian, English) as listed in the public documents.
Inclusion criteria
- {"criterion_text":"- 1. Age ≥ 18 (or age of legal consent, whichever is older) to < 70 years at the time of screening Type of Participant and Disease Characteristics\n- 2. Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on 2 occasions at least 6 months apart based on previous (within the past 12 months) or current laboratory documentation (any combination of these tests performed 6 months apart is acceptable)\n- 3. On locally approved NRTI therapy for at least 12 weeks prior to Day 1\n- 4. HBsAg > 0.05 IU/mL at screening\n- 5. Positive HDV antibody for at least 6 months prior to screening and HDV RNA ≥ 500 IU/mL at screening\n- 6. Serum alanine aminotransferase (ALT) > ULN and < 5 x ULN Weight\n- 7. Body Mass Index (BMI) ≥ 18 kg/m2 to ≤ 40 kg/m2 Sex and Contraceptive/Barrier Requirements\n- 8. Female participants must have a negative pregnancy test or confirmation of postmenopausal status. Postmenopausal status is defined as 12 months with no menses without an alternative medical cause (see Section 10.7 for additional details). Women of childbearing potential (WOCBP) must have a negative blood pregnancy test at screening and a negative urine pregnancy test on Day 1, cannot be breast feeding, and must be willing to use highly effective methods of contraception (Section 10.7) 14 days before study intervention administration through 48 weeks after the last dose of VIR-2218 or VIR-3434. Female participants must also agree to refrain from egg donation and in vitro fertilization from the time of study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434.\n- 9. Male participants with female partners of childbearing potential must agree to meet 1 of the following contraception requirements from the time of study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP (Section 10.7). Male participants must also agree to not donate sperm from the time of first study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434. Informed Consent\n- 10. Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol\n- For the rest of the inclusion criteria, please refer to the study protocol."}
Exclusion criteria
- {"criterion_text":"- 1. History of clinically significant liver disease from non-HBV and non- HDV etiology as determined by the investigator\n- 2. History of clinically significant immune complex disease as determined by the investigator\n- 3. History of clinically significant autoimmune disorder as determined by the investigator\n- 4. History of HBV-related extrahepatic disease, including but not limited to HBV-related rash, arthritis, or glomerulonephritis\n- 5. History of allergic reactions, hypersensitivity, or intolerance to study intervention, its metabolites or excipients\n- 6. Anti-HBs >10 mIU/L at screening\n- 7. Corrected QT interval (QTc) > 450 milliseconds\n- 8. ALT or AST ≥ 5 x ULN\n- 9. Total bilirubin > 2.0 mg/dL\n- 10. Serum albumin < 30 g/L\n- 11. Absolute neutrophil count < 1,000/mm3 (/μL)\n- 12. International normalized ratio (INR) > 1.5\n- 13. Hemoglobin < 8 g/dL\n- 14. History of anaphylaxis\n- 15. History of malignancy diagnosed or treated within 5 years (localized treatment of squamous or noninvasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); participants under evaluation for malignancy are not eligible\n- 16. History of or listed for bone marrow or solid organ transplant\n- 17. Known active infection other than chronic HBV and HDV infection or any clinically significant acute condition such as fever (> 38° C) or acute respiratory illness within 7 days prior to Day 1\n- 18. Coinfection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV) or hepatitis E virus (HEV). Participants who are HCV antibody positive and HCV RNA negative are eligible. Participants who are HAV or HEV immunoglobulin M antibody (IgM) positive can be enrolled if asymptomatic and HAV or HEV immunoglobulin G antibody (IgG) positive.\n- 19. Any clinically significant medical or psychiatric condition that may interfere with study intervention, assessment, or compliance with the protocol or otherwise makes the participant unsuitable for participation in the study, as determined by the investigator. Participants with controlled Diabetes Mellitus are eligible.\n- 20. Acute or worsening chronic hepatitis, fluctuating or rapidly deteriorating hepatic function or use of any therapy known to exacerbate hepatic dysfunction in the opinion of the investigator. For the rest of the exclusion criteria, please refer to the study protocol."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline and alanine aminotransferase (ALT) normalization (ALT < upper limit of normal [ULN]) at Week 24.","definition_or_measurement_approach":"HDV RNA measured against limit of detection (LOD); endpoint counts participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease from baseline AND who have ALT normalization defined as ALT < ULN at Week 24."}
- {"endpoint_text":"- Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)","definition_or_measurement_approach":"Safety assessed by recording incidence, severity and relatedness of TEAEs and SAEs during the study period per standard pharmacovigilance reporting."}
Secondary endpoints
- {"endpoint_text":"- Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline and ALT normalization at Week 12, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"Same virologic and ALT normalization criteria assessed at specified weeks."}
- {"endpoint_text":"- Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"HDV RNA undetectable (< LOD) or ≥2 log10 decrease from baseline at specified weeks."}
- {"endpoint_text":"- Proportion of participants with undetectable HDV RNA (< LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"Proportion with HDV RNA below LOD at specified weeks."}
- {"endpoint_text":"- Proportion of participants with HDV RNA < lower limit of quantitation (LLOQ) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"HDV RNA < LLOQ measured at specified weeks."}
- {"endpoint_text":"- Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"Change in quantitative HDV RNA from baseline to each specified week."}
- {"endpoint_text":"- Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.","definition_or_measurement_approach":"ALT normalization defined as ALT < ULN at specified weeks."}
- {"endpoint_text":"- Incidence of ADA and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR-3434).","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADA) incidence and titers at specified visits up to Week 192 for VIR-3434-treated cohorts."}
- {"endpoint_text":"- Change from baseline in liver fibrosis at Week 48, Week 96, Week 144, and Week 192.","definition_or_measurement_approach":"Liver fibrosis assessed versus baseline at specified weeks (methodology per protocol)."}
- {"endpoint_text":"- Change from baseline in Model for End Stage Liver Disease (MELD) score at Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 144, and Week 192.","definition_or_measurement_approach":"Change in MELD score from baseline at listed timepoints."}
- {"endpoint_text":"- Change from baseline CPT score at Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.","definition_or_measurement_approach":"Change in Child-Pugh-Turcotte (CPT) score from baseline at listed timepoints."}
Recruitment
- Planned Sample Size
- 119
- Recruitment Window Months
- 75
- Consent Approach
- Participants must be capable of giving signed informed consent. ICFs and subject information sheets are provided, including adult ICFs and separate ICFs for pregnant participants/partners and optional substudies. ICFs are available in multiple country/language versions (examples in the public documents: Dutch, French, German, Italian, Romanian, Bulgarian, English). No assent process for minors is applicable since only adults (≥18) are eligible.
Geography
- Total Number Of Sites
- 12
- Total Number Of Participants
- 119
Netherlands
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 16-10-2025
- Processing Time Days
- 423
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- MDL
- Principal Investigator Name
- Milan Sonneveld
- Principal Investigator Email
- m.j.sonneveld@erasmusmc.nl
- Contact Person Name
- Milan Sonneveld
- Contact Person Email
- m.j.sonneveld@erasmusmc.nl
France
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 17-10-2025
- Processing Time Days
- 424
- Number Of Sites
- 3
- Number Of Participants
- 35
Sites
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Hépatologie
- Principal Investigator Name
- Caroline Jezequel
- Principal Investigator Email
- caroline.jezequel@chu-rennes.fr
- Contact Person Name
- Caroline Jezequel
- Contact Person Email
- caroline.jezequel@chu-rennes.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Hepatologie
- Principal Investigator Name
- Sophie Metivier
- Principal Investigator Email
- metivier.s@chu-toulouse.fr
- Contact Person Name
- Sophie Metivier
- Contact Person Email
- metivier.s@chu-toulouse.fr
- Site Name
- Hopital Beaujon
- Department Name
- Hepatologie
- Principal Investigator Name
- Tarik Asselah
- Principal Investigator Email
- tarik.asselah@aphp.fr
- Contact Person Name
- Tarik Asselah
- Contact Person Email
- tarik.asselah@aphp.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 423
- Number Of Sites
- 1
- Number Of Participants
- 15
Sites
- Site Name
- Medizinische Hochschule Hannover
- Department Name
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
- Principal Investigator Name
- Katja Deterding
- Principal Investigator Email
- deterding.katja@mh-hannover.de
- Contact Person Name
- Katja Deterding
- Contact Person Email
- deterding.katja@mh-hannover.de
Italy
- Earliest CTIS Part Ii Submission Date
- 15-08-2024
- Latest Decision Or Authorization Date
- 14-10-2025
- Processing Time Days
- 426
- Number Of Sites
- 2
- Number Of Participants
- 10
Sites
- Site Name
- Azienda Ospedaliero Universitaria Pisana
- Department Name
- Unità Operativa di Epatologia
- Principal Investigator Name
- Maurizia Rossana Brunetto
- Principal Investigator Email
- maurizia.brunetto@unipi.it
- Contact Person Name
- Maurizia Rossana Brunetto
- Contact Person Email
- maurizia.brunetto@unipi.it
- Site Name
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
- Department Name
- UOC Gastroenterologia ed Epatologia
- Principal Investigator Name
- Pietro Lampertico
- Principal Investigator Email
- pietro.lampertico@unimi.it
- Contact Person Name
- Pietro Lampertico
- Contact Person Email
- pietro.lampertico@unimi.it
Romania
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 20-10-2025
- Processing Time Days
- 423
- Number Of Sites
- 1
- Number Of Participants
- 30
Sites
- Site Name
- Institutul National De Boli Infectioase Prof.Dr.Matei Bals
- Department Name
- Infectious Diseases
- Principal Investigator Name
- Anca Streinu-Cercel
- Principal Investigator Email
- anca.streinucercel@gmail.com
- Contact Person Name
- Anca Streinu-Cercel
- Contact Person Email
- anca.streinucercel@gmail.com
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 15-10-2025
- Processing Time Days
- 423
- Number Of Sites
- 4
- Number Of Participants
- 25
Sites
- Site Name
- Acibadem City Clinic Tokuda University Hospital EAD
- Department Name
- Department of Gastroenterology to Clinic of Gastroenterology
- Principal Investigator Name
- Rozalina Balabanska
- Principal Investigator Email
- rozabalabanska@abv.bg
- Contact Person Name
- Rozalina Balabanska
- Contact Person Email
- rozabalabanska@abv.bg
- Site Name
- Umbal - Prof. D-R Stoyan Kirkovich AD
- Department Name
- Department of Gastroenterology
- Principal Investigator Name
- Mariana Radicheva
- Principal Investigator Email
- dr.mradicheva@gmail.com
- Contact Person Name
- Mariana Radicheva
- Contact Person Email
- dr.mradicheva@gmail.com
- Site Name
- Diagnostic-Consultative Center Alexandrovska EOOD
- Principal Investigator Name
- Diana Petrova
- Principal Investigator Email
- prof.petrova@mail.bg
- Contact Person Name
- Diana Petrova
- Contact Person Email
- prof.petrova@mail.bg
- Site Name
- University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD
- Department Name
- Clinic of Gastroenterology
- Principal Investigator Name
- Krassimir Antonov
- Principal Investigator Email
- krasi_antonov@abv.bg
- Contact Person Name
- Krassimir Antonov
- Contact Person Email
- krasi_antonov@abv.bg
Sponsor
Primary sponsor
- Full Name
- Vir Biotechnology Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- PPD Development LP
- Responsibilities
- sponsorDuties codes: [1,12,2,5]
- Name
- Pharmaceutical Product Development LLC
- Responsibilities
- sponsorDuties code: [4]
- Name
- QPS LLC
- Responsibilities
- PK Analysis (sponsorDuties code 15)
- Name
- Syneos Health Inc.
- Responsibilities
- Sites Payment (sponsorDuties code 15)
Third parties
- {"country":"Romania","full_name":"Arensia Exploratory Medicine S.R.L.","duties_or_roles":"sponsorDuties codes: [12,2,5]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"Exploratory analysis (sponsorDuties code 15; value: 'Exploratory analysis')","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Immunology/Virology Analysis (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: [14,15] (value for 15: 'IMP EU Returns for the EU sites')","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"PK/ADA Analysis (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [1,12,2,5]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties code: [4]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"QPS LLC","duties_or_roles":"PK Analysis (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH (Rheinfelden address)","duties_or_roles":"sponsorDuties codes: [14,15] (value for 15: 'IMP EU Distribution for the EU sites')","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"Immunology Analysis (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Netherlands","full_name":"DDL Diagnostic Laboratory B.V.","duties_or_roles":"Virology Analysis (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: [3]","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Germany","full_name":"ARENSIA Exploratory Medicine GmbH","duties_or_roles":"sponsorDuties codes: [12,15,5] (value for 15: 'Feasibility and Contract negotiation with PI for Romania')","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Sites Payment (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: [7]","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"CyTOF Analysis (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Biomontr Labs","duties_or_roles":"HBV RNA analysis (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"Pharmacovigilance Services (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"ADA Analysis (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioagilytix Labs LLC (alternate entry)","duties_or_roles":"sponsorDuties code: [15]","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- VIR-3434
- Active Substance
- TOBEVIBART
- Modality
- Monoclonal antibody
- Routes Of Administration
- SUBCUTANEOUS USE
- Route
- SUBCUTANEOUS
- Authorisation Status
- Authorised (prodAuthStatus=1)
- Maximum Dose
- 300 mg (maxDailyDoseAmount)
- Investigational Product Name
- VIR-2218
- Active Substance
- ELEBSIRAN
- Modality
- Oligonucleotide
- Routes Of Administration
- SUBCUTANEOUS USE
- Route
- SUBCUTANEOUS
- Authorisation Status
- Authorised (prodAuthStatus=1)
- Maximum Dose
- 200 mg (maxDailyDoseAmount)
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