TOBEVIBART for Chronic Hepatitis D (HDV) infection

Inclusion criteria

• {"criterion_text":"- Adult men and women aged ≥ 18 years (or age of legal consent, whichever is older) to ≤ 70 years at the time of signing informed consent\n- Positive HDV antibody or positive HDV RNA PCR result for at least 6 months prior to screening and HDV RNA ≥ 500 IU/mL at screening\n- Noncirrhotic or compensated cirrhotic liver disease at screening\n- Serum alanine aminotransferase (ALT) > ULN and < 5 x ULN\n- Body mass index (BMI) ≥ 18 kg/m2 to ≤ 40 kg/m2\n- On NRTI (nucleos(t)ide reverse transcriptase inhibitor) therapy against HBV for at least 12 weeks prior to Day 1 or have HBV DNA < 10 IU/ml at screening, and currently on one of the following NRTI therapies starting at day 1: tenofovir alafenamide, tenofovir disoproxil fumarate, or entecavir\n- Note: Other protocol defined Inclusion criteria may apply"}

Exclusion criteria

• {"criterion_text":"- 1. Current or prior history of any of the following: a. Clinically significant laboratory abnormalities, co-morbid medical condition (other than HBV/HDV coinfection) or planned medical procedure that may interfere with the participant’s treatment, assessment, or compliance with the protocol. b. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. c. Current or previous (within 24 months of screening) clinically identified hepatic decompensation d. Bone marrow, peripheral blood stem-cell or solid organ transplantation e. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. f. Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; ductal carcinoma in situ and cervical carcinoma in situ is allowed if appropriately treated prior to screening); participants under evaluation for malignancy are not eligible. g. Significant drug allergy (such as anaphylaxis or hepatotoxicity)\n- One or more additional known primary or secondary causes of liver disease, other than hepatitis B or hepatitis D (i.e., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, Wilson’s disease, other congenital or metabolic condition affecting the liver, congestive heart failure, etc).\n- History of clinically significant immune complex disease as determined by the Investigator.\n- History of anaphylaxis, allergic reactions, hypersensitivity, or intolerance to study drug, study drug component (ex. Oligonucleotide and/or GalNAc) its metabolites or excipients\n- Participants with active HCV (participants with HCV antibodies can be enrolled if screening HCV RNA PCR test is negative).\n- Participants with uncontrolled HIV-1 infection (defined as HIV-1 RNA PCR value above the lower limit of assay detection with CD4+ T-cell counts < 500/mm3 within the last 12 months) or any HIV-2 infection\n- Note: Other protocol defined Exclusion criteria may apply"}

Primary endpoints

• {"endpoint_text":"- HDV RNA < LLOQ (lower limit of quantification), TND (target not detected) and ALT (alanine aminotransferase) normalization (ALT ≤ ULN) at Week 48 for Arm 1 vs at Week 12 for Arm 2.","definition_or_measurement_approach":"Virological response defined as HDV RNA below the assay LLOQ or target not detected (TND); biochemical response defined as ALT ≤ ULN; assessed at Week 48 for Arm 1 and at Week 12 for Arm 2."}
• {"endpoint_text":"- Primary safety Incidence of TEAEs and SAEs through Week 12.","definition_or_measurement_approach":"Safety endpoint measured as incidence (count and proportion) of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to Week 12."}

Secondary endpoints

• {"endpoint_text":"- HDV RNA < LLOQ, TND at Week 48 for Arm 1 vs at Week 12 for Arm 2 (key secondary endpoint).","definition_or_measurement_approach":"Virological response as HDV RNA < LLOQ or TND at specified weeks (Week 48 for Arm 1 vs Week 12 for Arm 2)."}
• {"endpoint_text":"- HDV RNA < LLOQ at Week 48 for Arm 1 vs at Week 12 for Arm 2.","definition_or_measurement_approach":"HDV RNA below LLOQ at specified timepoints."}
• {"endpoint_text":"- Change from baseline in HDV RNA at Week 48 for Arm 1 vs at Week 12 for Arm 2","definition_or_measurement_approach":"Quantitative change from baseline in HDV RNA at specified timepoints."}
• {"endpoint_text":"- ALT ≤ ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2","definition_or_measurement_approach":"ALT value ≤ ULN at specified weeks."}
• {"endpoint_text":"- ALT < 1.25 × ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2","definition_or_measurement_approach":"ALT value < 1.25 × ULN at specified weeks."}
• {"endpoint_text":"- Change from baseline in ALT at Week 48 for Arm 1 vs at Week 12 for Arm 2","definition_or_measurement_approach":"Change from baseline in serum ALT at specified weeks."}
• {"endpoint_text":"- HDV RNA < LLOQ, TND and ALT < 1.25 × ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2","definition_or_measurement_approach":"Composite virological and biochemical endpoint combining HDV RNA < LLOQ/TND and ALT < 1.25 × ULN at specified weeks."}
• {"endpoint_text":"- HDV RNA < LLOQ, TND and ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Long-term virological and biochemical outcomes assessed at 48, 96, 144, 192, and 240 weeks on treatment."}
• {"endpoint_text":"- HDV RNA < LLOQ and ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Virological and ALT normalization assessed at long-term timepoints."}
• {"endpoint_text":"- HDV RNA < LLOQ, TND and ALT < 1.25 × ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Composite virological and biochemical endpoint at multiple long-term timepoints."}
• {"endpoint_text":"- HDV RNA < LLOQ, TND at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Virological suppression (HDV RNA < LLOQ or TND) at multiple long-term timepoints."}
• {"endpoint_text":"- HDV RNA < LLOQ at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Quantitative HDV RNA < LLOQ at long-term visits."}
• {"endpoint_text":"- Change from baseline in HDV RNA at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Change from baseline in HDV RNA at specified long-term timepoints."}
• {"endpoint_text":"- ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"ALT normalization assessed at long-term timepoints."}
• {"endpoint_text":"- ALT < 1.25 × ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"ALT below 1.25 × ULN at long-term visits."}
• {"endpoint_text":"- Change from baseline in ALT at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Change from baseline in ALT at multiple long-term timepoints."}
• {"endpoint_text":"- Change from baseline in liver stiffness as measured by liver elastography at 48, 96,144, 192 and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Change in liver stiffness measured by elastography at specified long-term visits."}
• {"endpoint_text":"- Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by 48, 96, 144, 192and 240 weeks of tobevibart + elebsiran treatment","definition_or_measurement_approach":"Incidence of clinical decompensation or CPT score ≥7 at long-term timepoints."}
• {"endpoint_text":"- Incidence of HCC and progression to liver failure requiring transplantation or resulting in death by 48, 96. 144, 192 and 240 weeks of tobevibart + elebsiran treatment.","definition_or_measurement_approach":"Incidence of hepatocellular carcinoma (HCC) or progression to liver failure requiring transplant or causing death at long-term timepoints."}
• {"endpoint_text":"- Secondary safety: Incidence of TEAEs and SAEs through 48, 96, 144, 192and 240 weeks of treatment","definition_or_measurement_approach":"Incidence of TEAEs and SAEs assessed up to multiple long-term timepoints."}

Methods

• Online advertisements / banners (K2_Recruitment Material_Online Advertisments_Banners and country-specific versions)
• Social media clinical trial posts (K2_Recruitment Material_Online Advertisments_Social Media Clinical Trial Posts and country-specific versions)
• Patient brochures (K2_Recruitment Material_Patient Brochure and country-specific versions; printed and digital patient brochures)
• Digital patient brochure and digital materials (K2_Recruitment Material_Digital Patient Brochure)
• Educational 'About Clinical Research Studies' brochures and Hepatitis D specific brochures (K2_Recruitment Material_About Clinical Research Studies Brochure; K2_Recruitment Material_Hepatitis D Brochure) - country-specific versions available (DE/RO/FR)

Romania

Earliest CTIS Part Ii Submission Date

15-04-2025

Latest Decision Or Authorization Date

19-05-2025

Processing Time Days

34

Number Of Sites

3

Number Of Participants

19

Germany

Earliest CTIS Part Ii Submission Date

04-04-2025

Latest Decision Or Authorization Date

12-05-2025

Processing Time Days

38

Number Of Sites

5

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

24-04-2025

Latest Decision Or Authorization Date

19-05-2025

Processing Time Days

25

Number Of Sites

5

Number Of Participants

4

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

Data Management CRO - FSP; contact email: EUCTRInquiry.sm@ppd.com

Name

IQVIA Limited

Responsibilities

Clinical operations and study support, eCOA/tablet and other study services; contact email: eu_clinical_trials_information@iqvia.com

Name

4g Clinical LLC

Responsibilities

Clinical operations support (sponsorDuties code 3); contact email: vir@4gclinical.com

Name

QPS LLC

Responsibilities

Laboratory/assay/vendor support (sponsorDuties code 4); contact email: GBASCG@qps.com

Name

Syneos Health Inc.

Responsibilities

CTA, budget and ancillary document support; contact email: sample.receipt@syneoshealth.com

Third parties

• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"sponsorDuties codes: [4]; contact email: GBASCG@qps.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"ARENSIA Exploratory Medicine GmbH","duties_or_roles":"sponsorDuties codes: [5]; contact email: betty.birova@arensia-em.com","organisation_type":"SME"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]; contact email: Sample_management@frontagelab.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Edetek Inc.","duties_or_roles":"sponsorDuties codes: [10,15]; roles: Data visualization and Statistical support; contact email: info@EDETEK.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties codes: [4]; contact email: Customerservices@bioagilytix.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Ubc Late Stage (UK) Limited","duties_or_roles":"sponsorDuties codes: [8]; contact email: VirBioPV@ubc.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Client-Pharma Limited","duties_or_roles":"sponsorDuties codes: [15]; value: Water for injection vendor; contact email: kam@clientpharma.com","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"DDL Diagnostic Laboratory B.V.","duties_or_roles":"sponsorDuties codes: [4]; contact email: evert.hoefnagel@ddl.nl","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [1,12,15,5]; roles include study operational support, eCOA/tablet, study services; contact email: eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: [3]; contact email: vir@4gclinical.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"FGK Representative Service B.V.","duties_or_roles":"sponsorDuties codes: [15]; value: EU legal Representative for Sponsor; contact email: clinical.studies@fgk-rs.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: [15,6]; value: Data Management CRO - FSP; contact email: EUCTRInquiry.sm@ppd.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact email: info@medidata.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties codes: [4]; contact email: q2_eu_clinical_trials_information@q2labsolutions.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Denmark","full_name":"Sply ApS","duties_or_roles":"sponsorDuties codes: [15]; value: User Acceptance Testing for IRT; contact email: ap@ct-sply.com","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Cerba","duties_or_roles":"sponsorDuties codes: [4]; contact email: vir-chdv-v203@cerbaresearch.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: [15]; value: CTA, budget ancillary documents; contact email: sample.receipt@syneoshealth.com","organisation_type":"Pharmaceutical company"}
• {"country":"Romania","full_name":"Arensia Exploratory Medicine S.R.L.","duties_or_roles":"sponsorDuties codes: [12,2,5]; contact email: anamaria.iancu@arensia-em.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"sponsorDuties codes: [4]; contact email: vir-chdv-v203@cerbaresearch.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: [15]; value: IMP Distribution, QP Release; contact email: Rheinfelden.and.weil.reception@thermofisher.com","organisation_type":"Pharmaceutical company"}