A Study to Evaluate Tobevibart+Elebsiran versus Bulevirtide in Chronic HDV Infection

Phase 2

Not yet recruiting

• Conditions: Chronic Hepatitis D Virus (HDV) Infection

• Registration Number: 2024-520062-54-00
• Lead Sponsor: Vir Biotechnology Inc.

Brief Summary

(Primary Objective 1) To evaluate the antiviral efficacy of tobevibart+elebsiran vs BLV (bulevirtide) in participants with chronic HDV infection (Part 1)

(Primary Objective 2) To evaluate the efficacy of tobevibart+elebsiran in achieving SVR (sustained virologic response) in participants who systematically interrupt treatment per protocol (Part 2)

(Primary Objective 3) To evaluate the safety of tobevibart+elebsiran and BLV in participants with chronic HDV infection (Primary Safety)

Detailed Description

Not available

Study Timeline

• Study First Posted: 2025-06-11
• Last Update Posted: 2025-06-16

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 53

Inclusion Criteria

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

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.

Noncirrhotic or compensated cirrhotic liver disease at screening

BMI ≥ 18 kg/m2 to ≤ 40 kg/m2

On NRTI therapy against HBV for at least 12 weeks prior to Day 1 or have HBV DNA < 20 IU/ml at screening, and currently on locally approved NRTI therapy. Participants must be on one of the following NRTI therapies: tenofovir alafenamide (taken alone or as part of fixed-dose combination therapy), tenofovir disoproxil fumarate (taken alone or as part of fixed-dose combination therapy), or entecavir.

Note: Other protocol defined Inclusion criteria may apply

Exclusion Criteria

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)

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).

History of clinically significant immune complex disease as determined by the Investigator.

History of anaphylaxis, allergic reactions, hypersensitivity, or intolerance to study drug, its metabolites or excipients

Participants with active HCV (participants with HCV antibodies can be enrolled if screening HCV RNA PCR test is negative).

Participants with HIV infection can be enrolled if CD4+ T-cell counts are > 500/mm3 and HIV RNA PCR is below the limit of detection for at least 12 months

Any previous treatment with bulevirtide (BLV).

ALT ≥ 5 × ULN

Note: Other protocol defined Exclusion criteria may apply

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
HDV RNA < Lower Limit of Quantification (LLOQ), Target Not Detected (TND) at Week 48 (Part 1)		HDV RNA < Lower Limit of Quantification (LLOQ), Target Not Detected (TND) at Week 48 (Part 1)
Part 2: HDV RNA < LLOQ, TND 24 weeks after end of treatment interruption (Week 120)		Part 2: HDV RNA < LLOQ, TND 24 weeks after end of treatment interruption (Week 120)
Primary safety – Incidence of TEAEs and SAEs through Week 48		Primary safety – Incidence of TEAEs and SAEs through Week 48

Secondary Outcome Measures

Name	Time	Method
• HDV RNA < LLOQ at Week 48 • Change from baseline in HDV RNA at Week 48		• HDV RNA < LLOQ at Week 48 • Change from baseline in HDV RNA at Week 48
Change from baseline in ALT at Week 48		Change from baseline in ALT at Week 48
Change from baseline in liver stiffness as measured by liver elastography at Week 48		Change from baseline in liver stiffness as measured by liver elastography at Week 48
• Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by Week 48 • Incidence of HCC and progression to liver failure requiring transplantation or resulting in death by Week 48		• Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by Week 48 • Incidence of HCC and progression to liver failure requiring transplantation or resulting in death by Week 48
• Change from baseline in HBsAg at Week 48 • Categorical summary of HBsAg at Week 48		• Change from baseline in HBsAg at Week 48 • Categorical summary of HBsAg at Week 48
• HDV RNA < LLOQ, TND at Week 96, Week 120, Week 144, Week 192 and Week 240 • HDV RNA < LLOQ at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HDV RNA at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HDV RNA from tobevibart+elebsiran interruption at Week 96 to Week 120, Week 144, Week 192 and Week 240		• HDV RNA < LLOQ, TND at Week 96, Week 120, Week 144, Week 192 and Week 240 • HDV RNA < LLOQ at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HDV RNA at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HDV RNA from tobevibart+elebsiran interruption at Week 96 to Week 120, Week 144, Week 192 and Week 240
•Change from baseline in ALT at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in ALT from tobevibart+elebsiran interruption at Week 96 to Week 120, Week 144, Week 192 and Week 240		•Change from baseline in ALT at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in ALT from tobevibart+elebsiran interruption at Week 96 to Week 120, Week 144, Week 192 and Week 240
• Change from baseline in liver stiffness as measured by liver elastography at Week 96, Week 120, Week 144, Week 192 and Week 240		• Change from baseline in liver stiffness as measured by liver elastography at Week 96, Week 120, Week 144, Week 192 and Week 240
• Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by Week 96, Week 120, Week 144, Week 192 and Week 240 • Incidence of HCC and progression to liver failure requiring transplantation or resulting in death by Week 96, Week 120, Week 144, Week 192 and Week 240		• Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by Week 96, Week 120, Week 144, Week 192 and Week 240 • Incidence of HCC and progression to liver failure requiring transplantation or resulting in death by Week 96, Week 120, Week 144, Week 192 and Week 240
• Categorical summary of HBsAg at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HBsAg at Week 96, Week 120, Week 144, Week 192 and Week 240		• Categorical summary of HBsAg at Week 96, Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HBsAg at Week 96, Week 120, Week 144, Week 192 and Week 240
• Incidence of TEAEs and SAEs through Week 96, Week 120, Week 144, Week 192 and Week 240 (secondary safety)		• Incidence of TEAEs and SAEs through Week 96, Week 120, Week 144, Week 192 and Week 240 (secondary safety)
• Incidence of AEs, SAEs and lab abnormalities from time of tobevibart+elebsiran interruption (Week 96) through Week 120, Week 144, Week 192 and Week 240 (secondary safety)		• Incidence of AEs, SAEs and lab abnormalities from time of tobevibart+elebsiran interruption (Week 96) through Week 120, Week 144, Week 192 and Week 240 (secondary safety)

Trial Locations

Locations (34)

Universitair Ziekenhuis Antwerpen; 🇧🇪 Edegem, Belgium

Hopital Erasme; 🇧🇪 Anderlecht, Belgium

SGS Belgium; 🇧🇪 Edegem, Belgium

Chu Brugmann; 🇧🇪 Brussels, Belgium

University Multiprofile Hospital For Active Treatment Saint Georgi EAD; 🇧🇬 Plovdiv, Bulgaria

University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD; 🇧🇬 Sofia, Bulgaria

Umbal - Prof. D-R Stoyan Kirkovich AD; 🇧🇬 Stara Zagora, Bulgaria

Acibadem City Clinic Tokuda University Hospital EAD; 🇧🇬 Sofiya, Bulgaria

Hopital Beaujon; 🇫🇷 Clichy, France

Centre Hospitalier Universitaire De Rennes; 🇫🇷 Rennes, France

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Universitair Ziekenhuis Antwerpen

🇧🇪Edegem, Belgium

Thomas Vanwolleghem

Site contact

+3238213324

thomas.vanwolleghem@uza.be