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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vir Biotechnology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

23 Jul 2025 → ongoing

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Vir Biotechnology, Inc.

External identifiers

EU CT number

2024-520062-54-00

ClinicalTrials.gov

NCT07142811

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy

(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)

Secondary objectives 12

1. To evaluate the antiviral efficacy of tobevibart+elebsiran vs BLV in participants with chronic HDV infection
2. To evaluate the impact of tobevibart+elebsiran vs BLV on ALT (alanine aminotransferase) in participants with chronic HDV infection
3. To evaluate the impact of tobevibart+elebsiran vs BLV on liver stiffness in participants with chronic HDV infection
4. To evaluate the impact of tobevibart+elebsiran vs BLV on end stage liver disease outcomes in participants with chronic HDV infection
5. To assess the effect of tobevibart+elebsiran vs BLV on HBsAg in participants with chronic HDV infection
6. To evaluate the long-term antiviral efficacy of tobevibart+elebsiran in participants with chronic HDV infection and efficacy of tobevibart+elebsiran in maintaining SVR over time in participants who systematically interrupt treatment per protocol
7. To evaluate the long-term impact of tobevibart+elebsiran on ALT in participants with chronic HDV infection and the impact of systematic tobevibart+elebsiran interruption per protocol on ALT
8. To evaluate liver stiffness in participants with chronic HDV infection after long-term treatment with tobevibart+elebsiran and in participants who systematically interrupt tobevibart+elebsiran treatment per protocol
9. To evaluate end stage liver disease outcomes in participants with chronic HDV infection after long-term treatment with tobevibart+elebsiran and in participants who systematically interrupt tobevibart+elebsiran treatment per protocol
10. To assess the antiviral effect of tobevibart+elebsiran on serum HBsAg after long-term treatment with tobevibart+elebsiran and in participants who systematically interrupt tobevibart+elebsiran treatment per protocol
11. To evaluate the long-term safety of tobevibart+elebsiran in participants with chronic HDV infection (Secondary safety)
12. To assess safety after systematic tobevibart+elebsiran interruption per protocol (Arm1) (Secondary safety)

Conditions and MedDRA coding

Chronic Hepatitis D Virus (HDV) Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. 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.
3. Noncirrhotic or compensated cirrhotic liver disease at screening
4. BMI ≥ 18 kg/m2 to ≤ 40 kg/m2
5. On NRTI therapy against HBV for at least 12 weeks prior to Day 1 or have HBV DNA < 10 IU/ml at screening, and currently on locally approved NRTI therapy. Participants must be on one of the following NRTI therapies starting at Day 1: 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.
6. Note: Other protocol defined Inclusion criteria may apply

Exclusion criteria 9

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)
2. 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).
3. History of clinically significant immune complex disease as determined by the Investigator.
4. History of anaphylaxis, allergic reactions, hypersensitivity, or intolerance to study drug, study drug components (e.g., oligonucleotide and/or GalNAc), its metabolites or excipients
5. Participants with active HCV (participants with HCV antibodies can be enrolled if screening HCV RNA PCR test is negative).
6. Participants with uncontrolled HIV-1 infection (defined as confirmed HIV-1 RNA>200 copies/mL or CD4+ T cell counts < 500/mm3 within the last 12 months) or any HIV-2 infection.
7. Any previous treatment with bulevirtide (BLV).
8. ALT ≥ 5 × ULN
9. Note: Other protocol defined Exclusion criteria may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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

Secondary endpoints 12

1. • HDV RNA < LLOQ at Week 48 • Change from baseline in HDV RNA at Week 48
2. Change from baseline in ALT at Week 48
3. Change from baseline in liver stiffness as measured by liver elastography at Week 48
4. • 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
5. • Change from baseline in HBsAg at Week 48 • Categorical summary of HBsAg at Week 48
6. • 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
7. •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
8. • Change from baseline in liver stiffness as measured by liver elastography at Week 96, Week 144, Week 192 and Week 240
9. • 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
10. • 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
11. • Incidence of TEAEs and SAEs through Week 96, Week 120, Week 144, Week 192 and Week 240 (secondary safety)
12. • 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vir Biotechnology Inc.

Sponsor organisation

Vir Biotechnology Inc.

Address

1800 Owens Street Suite 900

City

San Francisco

Postcode

94158-2388

Country

United States

Scientific contact point

Organisation

Vir Biotechnology Inc.

Contact name

Eileen Foy

Public contact point

Organisation

Vir Biotechnology Inc.

Contact name

Study Inquiry

Third parties 15

Locations

8 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 165 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications