A Study to Evaluate Investigational Therapies in Chronic Hepatitis D Virus 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

24 Nov 2022 → ongoing

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Vir Biotechnology, Inc.

External identifiers

EU CT number

2024-512203-40-00

EudraCT number

2022-001993-78

ClinicalTrials.gov

NCT05461170

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Therapy, Others, Pharmacokinetic, Pharmacogenetic

1. To evaluate the efficacy of VIR-2218 and VIR-3434 in participants with chronic HDV infection in Cohorts 2 and 3 only.
2. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Secondary objectives 10

1. 1. Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline and ALT normalization at Week 12, Week 48, Week 72, Week 96, Week 144 and Week 192.
2. 2. Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
3. 3. Proportion of participants with undetectable HDV RNA (< LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
4. 4. Proportion of participants with HDV RNA < lower limit of quantitation (LLOQ) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
5. 5. Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
6. 6. Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
7. 7. Incidence of ADA and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR-3434).
8. 8. Change from baseline in liver fibrosis at Week 48, Week 96, Week 144, and Week 192.
9. 9. Change from baseline in Model for End Stage Liver Disease (MELD) score at Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 144, and Week 192.
10. 10. Change from baseline CPT score at Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.

Conditions and MedDRA coding

Chronic Hepatitis D Virus (HDV) Infection

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Age ≥ 18 (or age of legal consent, whichever is older) to < 70 years at the time of screening Type of Participant and Disease Characteristics 2. Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on 2 occasions at least 6 months apart based on previous (within the past 12 months) or current laboratory documentation (any combination of these tests performed 6 months apart is acceptable) 3. On locally approved NRTI therapy for at least 12 weeks prior to Day 1 4. HBsAg > 0.05 IU/mL at screening 5. Positive HDV antibody for at least 6 months prior to screening and HDV RNA ≥ 500 IU/mL at screening 6. Serum alanine aminotransferase (ALT) > ULN and < 5 x ULN Weight 7. Body Mass Index (BMI) ≥ 18 kg/m2 to ≤ 40 kg/m2 Sex and Contraceptive/Barrier Requirements 8. Female participants must have a negative pregnancy test or confirmation of postmenopausal status. Postmenopausal status is defined as 12 months with no menses without an alternative medical cause (see Section 10.7 for additional details). Women of childbearing potential (WOCBP) must have a negative blood pregnancy test at screening and a negative urine pregnancy test on Day 1, cannot be breast feeding, and must be willing to use highly effective methods of contraception (Section 10.7) 14 days before study intervention administration through 48 weeks after the last dose of VIR-2218 or VIR-3434. Female participants must also agree to refrain from egg donation and in vitro fertilization from the time of study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434. 9. Male participants with female partners of childbearing potential must agree to meet 1 of the following contraception requirements from the time of study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP (Section 10.7). Male participants must also agree to not donate sperm from the time of first study intervention administration through 24 weeks after the last dose of VIR-2218 or VIR-3434. Informed Consent 10. Capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol For the rest of the inclusion criteria, please refer to the study protocol.

Exclusion criteria 1

1. Medical Conditions 1. History of clinically significant liver disease from non-HBV and non- HDV etiology as determined by the investigator 2. History of clinically significant immune complex disease as determined by the investigator 3. History of clinically significant autoimmune disorder as determined by the investigator 4. History of HBV-related extrahepatic disease, including but not limited to HBV-related rash, arthritis, or glomerulonephritis 5. History of allergic reactions, hypersensitivity, or intolerance to study intervention, its metabolites or excipients 6. Anti-HBs >10 mIU/L at screening 7. Corrected QT interval (QTc) > 450 milliseconds 8. ALT or AST ≥ 5 x ULN 9. Total bilirubin > 2.0 mg/dL 10. Serum albumin < 30 g/L 11. Absolute neutrophil count < 1,000/mm3 (/μL) 12. International normalized ratio (INR) > 1.5 13. Hemoglobin < 8 g/dL 14. History of anaphylaxis 15. History of malignancy diagnosed or treated within 5 years (localized treatment of squamous or noninvasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); participants under evaluation for malignancy are not eligible 16. History of or listed for bone marrow or solid organ transplant 17. Known active infection other than chronic HBV and HDV infection or any clinically significant acute condition such as fever (> 38° C) or acute respiratory illness within 7 days prior to Day 1 18. Coinfection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV) or hepatitis E virus (HEV). Participants who are HCV antibody positive and HCV RNA negative are eligible. Participants who are HAV or HEV immunoglobulin M antibody (IgM) positive can be enrolled if asymptomatic and HAV or HEV immunoglobulin G antibody (IgG) positive. 19. Any clinically significant medical or psychiatric condition that may interfere with study intervention, assessment, or compliance with the protocol or otherwise makes the participant unsuitable for participation in the study, as determined by the investigator. Participants with controlled Diabetes Mellitus are eligible. 20. Acute or worsening chronic hepatitis, fluctuating or rapidly deteriorating hepatic function or use of any therapy known to exacerbate hepatic dysfunction in the opinion of the investigator. For the rest of the exclusion criteria, please refer to the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline and alanine aminotransferase (ALT) normalization (ALT < upper limit of normal [ULN]) at Week 24.
2. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Secondary endpoints 10

1. Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline and ALT normalization at Week 12, Week 48, Week 72, Week 96, Week 144 and Week 192.
2. Proportion of participants with undetectable HDV RNA (< LOD) or ≥ 2 log10 decrease in HDV RNA from baseline at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
3. Proportion of participants with undetectable HDV RNA (< LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
4. Proportion of participants with HDV RNA < lower limit of quantitation (LLOQ) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
5. Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
6. Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192.
7. Incidence of ADA and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR-3434).
8. Change from baseline in liver fibrosis at Week 48, Week 96, Week 144, and Week 192.
9. Change from baseline in Model for End Stage Liver Disease (MELD) score at Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 144, and Week 192.
10. Change from baseline CPT score at Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.

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 19

Locations

6 EU/EEA countries · 12 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 49 files

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

Application history

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