A Study to Evaluate Tobevibart + Elebsiran 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

2 Jun 2025 → ongoing

Decision date (initial)

2025-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Vir Biotechnology, Inc.

External identifiers

EU CT number

2024-515919-22-00

ClinicalTrials.gov

NCT06903338

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Pharmacokinetic, Safety, Efficacy

To evaluate the efficacy of tobevibart + elebsiran compared with delayed treatment in participants with chronic HDV infection
To evaluate the safety of tobevibart + elebsiran in participants with chronic HDV infection

Secondary objectives 9

1. To evaluate the antiviral effect of tobevibart + elebsiran on HDV viremia compared with delayed treatment in participants with chronic HDV infection
2. To evaluate the impact of tobevibart + elebsiran on ALT compared with delayed treatment in participants with chronic HDV infection
3. To evaluate the efficacy of tobevibart + elebsiran compared with delayed treatment in participants with chronic HDV infection
4. To evaluate the long-term efficacy of tobevibart + elebsiran in participants with chronic HDV infection
5. To evaluate the long-term antiviral effect of tobevibart + elebsiran on HDV viremia in participants with chronic HDV infection
6. To evaluate the long-term impact of tobevibart + elebsiran on ALT in participants with chronic HDV infection
7. To evaluate the long-term impact of Tobevibart + elebsiran on liver stiffness in participants with chronic HDV infection
8. To evaluate the impact of tobevibart + elebsiran on end stage liver disease outcomes in participants with chronic HDV infection
9. To evaluate the safety of tobevibart + elebsiran in participants with chronic HDV infection

Conditions and MedDRA coding

Chronic Hepatitis D Virus (HDV) Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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. Serum alanine aminotransferase (ALT) > ULN and < 5 x ULN
5. Body mass index (BMI) ≥ 18 kg/m2 to ≤ 40 kg/m2
6. 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
7. Note: Other protocol defined Inclusion criteria may apply

Exclusion criteria 7

1. 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 component (ex. 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 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
7. Note: Other protocol defined Exclusion criteria may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. Primary safety Incidence of TEAEs and SAEs through Week 12.

Secondary endpoints 9

1. • HDV RNA < LLOQ, TND at Week 48 for Arm 1 vs at Week 12 for Arm 2 (key secondary endpoint). • HDV RNA < LLOQ at Week 48 for Arm 1 vs at Week 12 for Arm 2. • Change from baseline in HDV RNA at Week 48 for Arm 1 vs at Week 12 for Arm 2
2. • ALT ≤ ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2 • ALT < 1.25 × ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2 • Change from baseline in ALT at Week 48 for Arm 1 vs at Week 12 for Arm 2
3. • HDV RNA < LLOQ, TND and ALT < 1.25 × ULN at Week 48 for Arm 1 vs at Week 12 for Arm 2
4. • HDV RNA < LLOQ, TND and ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • HDV RNA < LLOQ and ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • HDV RNA < LLOQ, TND and ALT < 1.25 × ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment
5. • HDV RNA < LLOQ, TND at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • HDV RNA < LLOQ at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • Change from baseline in HDV RNA at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment
6. • ALT ≤ ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • ALT < 1.25 × ULN at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment • Change from baseline in ALT at 48, 96, 144, 192 and 240 weeks of tobevibart + elebsiran treatment
7. Change from baseline in liver stiffness as measured by liver elastography at 48, 96,144, 192 and 240 weeks of tobevibart + elebsiran treatment
8. • Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) by 48, 96, 144, 192and 240 weeks of tobevibart + elebsiran treatment • 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.
9. Secondary safety: Incidence of TEAEs and SAEs through 48, 96, 144, 192and 240 weeks of treatment

Investigational products

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

Test 2

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

Michael Chattergoon

Public contact point

Organisation

Vir Biotechnology Inc.

Contact name

Study Inquiry

Third parties 20

Locations

3 EU/EEA countries · 13 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 76 files

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

Application history

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