A Study to Evaluate Tobevibart+Elebsiran in Participants with Chronic HDV Infection Not Virologically Suppressed with Bulevirtide

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

9 Jul 2025 → ongoing

Decision date (initial)

2025-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

VIR Biotechnology Inc.

External identifiers

EU CT number

2024-519282-22-00

ClinicalTrials.gov

NCT07128550

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy

Part I: To evaluate the antiviral efficacy of tobevibart+elebsiran in participants with BLV treatment experience
Part 2: To evaluate the efficacy of tobevibart+elebsiran in achieving SVR in participants who systematically interrupt treatment

Secondary objectives 18

1. Part I: To evaluate long-term antiviral efficacy of tobevibart+elebsiran in participants with BLV treatment experience
2. Part I: To evaluate the effect of tobevibart+elebsiran on ALT in participants with BLV treatment experience
3. Part I: To evaluate the safety of tobevibart+elebsiran
4. Part I: To evaluate the impact of tobevibart+elebsiran on end stage liver disease outcomes
5. Part I: To evaluate the impact of tobevibart+elebsiran on liver stiffness in participants with BLV treatment experience
6. Part I: To evaluate the effect of tobevibart+elebsiran vs BLV on HBsAg in participants with BLV treatment experience
7. Part I: To evaluate the efficacy of tobevibart+elebsiran in participants with BLV treatment experience who have ALT ≤ ULN at baseline
8. Part I: To evaluate the efficacy of tobevibart+elebsiran in participants with BLV treatment experience who have ALT > ULN at baseline
9. Part II: To evaluate the efficacy of tobevibart+elebsiran in maintaining SVR over time in participants who systematically interrupt treatment
10. Part II: To evaluate long-term antiviral efficacy of tobevibart+elebsiran in participants who continue treatment in Part 2
11. Part II: To evaluate the impact of tobevibart+elebsiran interruption on ALT
12. Part II: To assess safety after tobevibart+elebsiran interruption for participants in Arm 1
13. Part II: To evaluate end stage liver disease outcomes in participants who systematically interrupt treatment and in participants with chronic HDV who continue treatment
14. Part II: To evaluate liver stiffness after tobevibart+elebsiran interruption in participants who systematically interrupt treatment and in participants with chronic HDV who continue treatment
15. Part II: To assess the antiviral effect of tobevibart+elebsiran on serum HBsAg
16. Part II: To evaluate long-term safety in participants who continue tobevibart+elebsiran after Week 96
17. Part II: To evaluate the efficacy of tobevibart+elebsiran in participants with BLV treatment experience who have ALT ≤ ULN at baseline
18. Part II: To evaluate the efficacy of tobevibart+elebsiran in participants with BLV treatment experience who have ALT > ULN at baseline

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. HDV RNA ≥ 500 IU/mL at screening
3. Receiving BLV 2 mg SC QD for ≥ 24 weeks at Day 1
4. Noncirrhotic or compensated cirrhotic liver disease at screening
5. Body mass index (BMI) ≥ 18 kg/m2 to ≤ 40 kg/m2
6. 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 a fixed-dose combination therapy), tenofovir disoproxil fumarate (taken alone or as part of a fixed-dose combination therapy), or entecavir

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 decompensationd. 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 (ie, 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 >200 copies/mL or CD4+ T-cell counts < 500/mm3 is within the last 12 months) or any HIV-2 infection.
7. Participants with HAV (participants who are HAV IgM positive can be enrolled if asymptomatic and HAV IgG positive).
8. Participants with HEV (participants who are HEV IgM positive can be enrolled if asymptomatic and HEV IgG positive). In cases where acute infection status cannot be determined by serologies a serum or stool HEV RT-PCR can be obtained. The participant is ineligible if PCR is positive
9. Current therapy or therapy within 24 weeks of of first study intervention administration with an immunomodulatory agent (eg, IFN-α), immune checkpoint inhibitors, immunosuppressants (eg, diseasemodifying antirheumatic drugs), cytotoxic or chemotherapeutic agent, or chronic systemic corticosteroids (equivalent of 10mg prednisone QD).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part I: HDV RNA < LLOQ, TND at Week 24
2. Part 2: HDV RNA < LLOQ, TND 24 weeks after end of treatment

Secondary endpoints 18

1. Part I: HDV RNA < LLOQ, TND at Week 48 and Week 96 Change from baseline in HDV RNA at Week 48 and Week 96
2. Part I: Change from baseline in ALT at Week 24, Week 48 and Week 96
3. Part I: Incidence of TEAEs and SAEs through Week 24, Week 48 and Week 96
4. Part I: • Incidence of decompensated cirrhosis (clinical event or CPT score ≥ 7) through Week 48 and Week 96 • Incidence of HCC or progression to liver failure requiring transplantation or resulting in death through Week 48 and Week 96
5. Part I: Change from baseline in liver stiffness as measured by liver elastography at Week 48 and Week 96
6. Part I: • Change from baseline in HBsAg at Week 24, Week 48 and Week 96 • Categorical summary of HBsAg at Week 24, Week 48 and Week 96
7. Part I: • ALT ≤ ULN and HDV RNA < LLOQ, TND at Week 24, Week 48 and Week 96 • ALT ≤ ULN at Week 24, Week 48 and Week 96
8. Part I: • ALT ≤ ULN and HDV RNA < LLOQ, TND at Week 24, Week 48 and Week 96 • ALT ≤ ULN at Week 24, Week 48 and Week 96
9. Part II: • HDV RNA < LLOQ, TND at 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
10. Part II: • HDV RNA < LLOQ, TND at Week 120, Week 144, Week 192 and Week 240 • Change from baseline in HDV RNA at Week 120, Week 144, Week 192 and Week 240
11. Part II: • Change from baseline in ALT from tobevibart+elebsiran interruption at Week 96 to Week 120, Week 144, Week 192 and Week 240
12. Part II: 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.
13. Part II: • Incidence of decompensation through Week 144, Week 192 and Week 240 • Incidence of HCC or progression to liver failure requiring transplantation or resulting in death through Week 144, Week 192 and Week 240
14. Part II: Change from baseline in liver stiffness as measured by liver elastography at Week 144, Week 192 and Week 240
15. Part II: Categorical summary of HBsAg at Week 120, Week 144, Week 192 and Week 240
16. Part II: TEAEs, SAEs through Week 120, Week 144, Week 192 and Week 240
17. Part II: • ALT ≤ ULN and HDV RNA < LLOQ, TND at Week 120, Week 144, Week 192 and Week 240 • ALT ≤ ULN at Week 120, Week 144, Week 192 and Week 240
18. Part II: ALT ≤ ULN and HDV RNA < LLOQ, TND at Week 120, Week 144, Week 192 and Week 240 • ALT ≤ ULN at Week 120, Week 144, Week 192 and Week 240

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

Leah Gaffney

Public contact point

Organisation

Vir Biotechnology Inc.

Contact name

Study Inquiry

Third parties 14

Locations

6 EU/EEA countries · 37 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 132 files

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

Application history

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