A Study to Evaluate Investigational Therapies in Chronic Hepatitis B Virus Infection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vir Biotechnology Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

30 Mar 2023 → 19 Aug 2025

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Vir Biotechnology, Inc.

External identifiers

EU CT number

2024-513176-17-00

EudraCT number

2022-002014-16

ClinicalTrials.gov

NCT05612581

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacoeconomic, Safety, Efficacy, Therapy, Pharmacokinetic

To evaluate the efficacy of the investigational regimen(s)

Secondary objectives 1

1. • To evaluate the safety and tolerability of the investigational regimens • To assess the effect of the investigational regimens on serum hepatitis B surface antigen (HBsAg) • To assess the effect of the investigational regimens on anti-HBs

Conditions and MedDRA coding

Chronic Hepatitis B Virus (HBV) Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Participants must meet the following inclusion criteria to be eligible for this Master Protocol. Additional clarifications and sub-protocol-specific criteria as described in respective sub-protocol(s) will be applicable: 1. Adult ≥ 18 years of age (or age of legal consent, whichever is older) 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 or current laboratory documentation (any combination of these tests performed 6 months apart is acceptable) Additional characteristics of the chronic HBV infection (eg: HBeAg status, HBV DNA level, ALT level) will be required based on the patient population (Table 3) included in respective sub-protocols 3. Besides chronic infection with HBV, must be in good health, determined from medical history, and no clinically significant findings from physical examination other than those expected in persons with cirrhosis, vital signs, and laboratory values 4. Female participants must have a negative pregnancy test or confirmation of postmenopausal status. Post-menopausal status is defined as 12 months with no menses without an alternative medical cause (see Section 10.5 for additional details). Women of child-bearing 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 10.5) 14 days before study intervention administration through period defined in sub-protocol. Female participants must also agree to refrain from egg donation and in vitro fertilization from the time of study intervention administration through period defined in sub-protocol 5. Male participants with female partners of child-bearing potential must agree to meet 1 of the following contraception requirements from the time of study intervention administration through period defined in sub- protocol: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP (Section 10.5). Male participants must also agree to not donate sperm from the time of first study intervention administration through period defined in sub-protocol 6. Able to understand and comply with the study requirements and able to provide written informed consent

Exclusion criteria 1

1. Participants are excluded from the study if any of the following criteria apply. Additional exclusion criteria may be described in respective sub- protocol(s): 1. History of clinically significant liver disease from non-HBV etiology 2. History or current evidence of hepatic decompensation, including ascites, hepatic encephalopathy, and/or esophageal or gastric varices 3. History or current suspicion of malignancy diagnosed or treated within 5 years (localized treatment of squamous or non-invasive 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. 4. History of bone marrow or solid organ transplant 5. Known active infection other than chronic HBV infection or any clinically significant acute condition such as fever (> 38° C) or acute respiratory or GI illness within 7 days prior to Day 1 6. Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV). Participants who are HCV antibody or HDV antibody positive, but have a documented negative HCV RNA or HDV RNA, respectively, are eligible. Participants with positive HAV immunoglobulin M (IgM) or HEV IgM but asymptomatic and with a positive HAV IgG or HEV immunoglobulin G (IgG) are eligible. 7. History or clinical evidence of alcohol or drug abuse within the 12 months before screening or a positive drug screen at screening unless it can be explained by a prescribed medication (the diagnosis and prescription must be approved by the investigator). Note: cannabis use is permitted 8. Received an investigational agent within 90 days or 5 half-lives (if known), whichever is longer, before study intervention administration or are active in the follow-up phase of another clinical study involving interventional treatment. Participants must also agree not to take part in any other interventional study at any time during their participation in this study, inclusive of the Follow-Up Period. 9. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at 24 weeks after discontinuation of all treatment • Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) at 24 weeks after discontinuation of all treatment • Proportion of participants with HBsAg loss (< 0.05 IU/mL) at 24 weeks post-end of treatment
2. • Proportion of participants achieving suppression of HBV DNA (< LLOQ [lower limit of quantitation]) with HBsAg loss (< 0.05 IU/mL) at the end of treatment • Proportion of participants with HBsAg loss (< 0.05 IU/mL) at the end of treatment • Mean change in serum HBsAg from baseline across timepoints in the study

Secondary endpoints 2

1. 1. Proportion of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) 2. Proportion of participants with serum HBsAg < 10 IU/mL at the end of treatment 3. Proportion of participants with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment 4. Serum HBsAg levels and change from baseline across timepoints in the study
2. 5. Serum HBsAg level at nadir during the study 6. Time to achieve nadir of serum HBsAg during the study 7. Time to achieve serum HBsAg loss (< 0.05 IU/mL) 8. Proportion of participants with HBsAg loss and anti-HBs seroconversion at end of treatment and at 24 weeks post-end of treatment

Investigational products

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

Test 4

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

Carey Hwang

Public contact point

Organisation

Vir Biotechnology Inc.

Contact name

Study Inquiry

Third parties 19

Locations

2 EU/EEA countries · 2 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 36 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