TOBEVIBART for Chronic hepatitis B | Chronic Hepatitis B Virus Infection

Inclusion criteria

• {"criterion_text":"- 1. Age ≥ 18 (or age of legal consent, whichever is older) to < 66 years"}
• {"criterion_text":"- 2. Body Mass Index (BMI) ≥ 18 kg/m2 to ≤ 35 kg/m2"}
• {"criterion_text":"- 3. 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)"}
• {"criterion_text":"- 4. On continuous NRTI therapy for at least 2 months prior to screening"}
• {"criterion_text":"- 5. HBV DNA < 100 IU/mL at screening"}
• {"criterion_text":"- 6. HBsAg > the lower limit of detection"}
• {"criterion_text":"- 7. Negative anti-HBs at screening"}
• {"criterion_text":"- 8. Besides chronic infection with HBV, must be in good health, determined from medical history, and no clinically significant findings from physical examination, vital signs, and laboratory values"}
• {"criterion_text":"- 9. Female subjects 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 6.4 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 6.4) 14 days before study drug administration through 48 weeks after the last dose of study drug. Female subjects must also agree to refrain from egg donation and in vitro fertilization from the time of study drug administration through 48 weeks after the last dose of study drug."}
• {"criterion_text":"- 10. Male subjects with female partners of childbearing potential must agree to meet 1 of the following contraception requirements from the time of study drug administration through 48 weeks after the last dose of study drug: documentation of vasectomy or azoospermia, or male condom use plus partner use of 1 of the contraceptive options listed for contraception for WOCBP (Section 6.4). Male subjects must also agree to not donate sperm from the time of first study drug administration through 48 weeks after the last dose of study drug."}
• {"criterion_text":"- 11. Willing to comply with the study requirements and able to provide written informed consent"}
• {"criterion_text":"- 12. Cohort 2b only: Previously enrolled in Cohort 1d of the VIR-2218-1001 study and completed the Treatment Period"}

Exclusion criteria

• {"criterion_text":"- 1. Significant fibrosis or cirrhosis as defined by having either a FibroScan result of > 8.5 kPa at screening or a liver biopsy within 1 year with Metavir F3 fibrosis or F4 cirrhosis."}
• {"criterion_text":"- 2. History of clinically significant liver disease from non-HBV etiology"}
• {"criterion_text":"- 3. History of hepatic decompensation, including ascites, hepatic encephalopathy, and/or esophageal or gastric varices"}
• {"criterion_text":"- 4. History of immune complex disease"}
• {"criterion_text":"- 5. History of an autoimmune disorder"}
• {"criterion_text":"- 6. History of HBV-related extrahepatic disease, including but not limited to HBV-related rash, arthritis, or glomerulonephritis"}
• {"criterion_text":"- 7. History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434"}
• {"criterion_text":"- 8. History of anaphylaxis"}
• {"criterion_text":"- 9. History 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); subjects under evaluation for malignancy are not eligible."}
• {"criterion_text":"- 10. History of bone marrow or solid organ transplant"}
• {"criterion_text":"- 11. Known active infection other than chronic HBV infection or any clinically significant acute condition such as fever (> 38° C) or acute respiratory illness within 7 days prior to Day 1"}
• {"criterion_text":"- 12. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV). Subjects who are HCV antibody or HDV antibody positive, but have a documented negative HCV RNA or HDV RNA, respectively, are eligible."}
• {"criterion_text":"- 13. Creatinine clearance (CLcr) < 30 mL/min as calculated by the Cockcroft-Gault formula at screening"}
• {"criterion_text":"- 14. Subject has the following laboratory parameters at screening by laboratory testing: a. ALT or aspartate aminotransferase (AST) > 3x ULN b. Direct bilirubin or INR > ULN"}
• {"criterion_text":"- 15. Regular consumption of more than 10 units of alcohol per week (1 unit = 1 glass of wine [125 mL] = 1 measure of spirits [30 mL] = one-half pint of beer [284 mL]), or more than 2 units of alcohol per day"}
• {"criterion_text":"- 16. 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"}
• {"criterion_text":"- 17. Use of any of the following systemic medications within 14 days before study drug administration and throughout the study: a. Paracetamol (acetaminophen) ≥ 3 g/day b. Isoniazid c. Systemic steroids (prednisone equivalent of > 10 mg/day) or other immunosuppressive agents (Note: corticosteroid administration for the treatment of immune-mediated AEs is allowed.) d. Parts A, C, and D only: theophylline e. Parts A, C, and D only: methadone"}
• {"criterion_text":"- 18. Received an investigational agent within 90 days or 5 half-lives (if known), whichever is longer, before study drug administration or are active in the follow-up phase of another clinical study involving interventional treatment. Subjects 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 and NRTI Discontinuation Monitoring Period. Note: Participants who previously enrolled in Cohort 1d of the VIR-2218-1001 study are eligible for Cohort 2b only."}
• {"criterion_text":"- 19. Receipt of an oligonucleotide (eg, siRNA, antisense oligonucleotide) with activity against HBV within 48 weeks before study drug administration Note: Participants who previously enrolled in Cohort 1d of the VIR-2218-1001 study and received VIR-2218 are eligible for Cohort 2b only."}
• {"criterion_text":"- 20. Receipt of VIR-3434 within 24 weeks prior to Day 1"}
• {"criterion_text":"- 21. Any clinically significant medical or psychiatric condition that may interfere with study treatment, assessment, or compliance with the protocol or otherwise makes the subject unsuitable for participation in the study, as determined by the investigator."}
• {"criterion_text":"- 22. Parts A, C, and D only: Known hypersensitivity or contraindication to an interferon product"}
• {"criterion_text":"- 23. Parts A, C, and D only: Current or prior history of psychosis, bipolar disorder, schizophrenia, moderate-severe depression, suicide ideation, attempt, or gesture, or high risk for suicide"}
• {"criterion_text":"- 24. Parts A, C, and D only: Current or prior history of clinically significant retinal disease"}
• {"criterion_text":"- 25. Parts A, C, and D only: Current or prior history of chronic uncontrolled hypoglycemia, or uncontrolled hyperglycemia/diabetes (defined as HbA1c ≥ 8%) at screening"}
• {"criterion_text":"- 26. Parts A, C, and D only: Current or prior history of colitis"}
• {"criterion_text":"- 27. Parts A, C, and D only: Serum lipase ≥ 2 times the ULN"}
• {"criterion_text":"- 28. Parts A, C, and D only: Thyroid stimulating hormone (TSH) and free T4 above the ULN or below the lower limit of normal (LLN)"}
• {"criterion_text":"- 29. Parts A, C, and D only: Platelets < 90,000 cells/mm3"}
• {"criterion_text":"- 30. Parts A, C, and D only: Absolute neutrophil count (ANC) < 1,500 cells/mm3"}
• {"criterion_text":"- 31. Clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening (as determined by the investigator)"}

Primary endpoints

• {"endpoint_text":"- • Proportion of subjects with treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects with serious adverse events (SAEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects with HBsAg loss (defined as undetectable HBsAg) at end of treatment","definition_or_measurement_approach":"HBsAg loss defined as undetectable HBsAg"}
• {"endpoint_text":"- • Proportion of subjects with HBsAg loss (defined as undetectable HBsAg) at 24 weeks post-end of treatment","definition_or_measurement_approach":"HBsAg loss defined as undetectable HBsAg"}

Secondary endpoints

• {"endpoint_text":"- • Proportion of subjects achieving functional cure (defined as undetectable HBsAg and sustained suppression of HBV DNA [below the lower limit of quantification (< LLOQ), target not detected (TND)] for ≥ 24 weeks after discontinuation of all treatment, including NRTIs)","definition_or_measurement_approach":"Functional cure defined as undetectable HBsAg and sustained suppression of HBV DNA (< LLOQ, TND) for ≥ 24 weeks after discontinuation of all treatment, including NRTIs"}
• {"endpoint_text":"- • Proportion of subjects with serum HBsAg < 10 IU/mL at end of treatment","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Absolute serum HBsAg and change from baseline across timepoints in the study","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Nadir and maximum reduction of serum of HBsAg from baseline","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Time to achieve nadir of serum HBsAg","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Time to achieve serum HBsAg loss","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects achieving sustained suppression of HBV DNA (< LLOQ for ≥ 24 weeks after discontinuation of all treatment, including NRTIs)","definition_or_measurement_approach":"Sustained suppression defined as HBV DNA < LLOQ for ≥ 24 weeks after discontinuation of all treatment, including NRTIs"}
• {"endpoint_text":"- • For HBeAg-positive subjects: proportion of subjects with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion","definition_or_measurement_approach":"HBeAg loss defined as undetectable HBeAg; anti-HBe seroconversion as conversion to anti-HBe positive"}
• {"endpoint_text":"- • For HBeAg-positive subjects: time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects with anti-HBs seroconversion","definition_or_measurement_approach":""}
• {"endpoint_text":"- • VIR-3434 PK parameters","definition_or_measurement_approach":"Pharmacokinetic parameters for VIR-3434 (PK sampling and analyses specified in protocol)"}
• {"endpoint_text":"- • Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434","definition_or_measurement_approach":"Incidence and titers measured by ADA assays (per protocol)"}
• {"endpoint_text":"- • Proportion of subjects meeting criteria for NRTI discontinuation","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Proportion of subjects meeting criteria for NRTI retreatment","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

30-07-2024

Latest Decision Or Authorization Date

26-11-2025

Processing Time Days

484

Number Of Sites

3

Number Of Participants

2

Romania

Earliest CTIS Part Ii Submission Date

31-07-2024

Latest Decision Or Authorization Date

02-12-2025

Processing Time Days

489

Number Of Sites

1

Number Of Participants

22

Primary sponsor

Full Name

Vir Biotechnology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Novotech (Australia) Pty Limited

Responsibilities

Various operational sponsor duties (codes: 1,10,12,13,2,5,6,7,8,9) as listed in CTIS

Name

Syneos Health Inc.

Responsibilities

Budget/contract negotiation; PK and ADA analyses for VIR-3434 (VIR-3434 PK analysis, VIR-3434 ADA analysis)

Name

Pharmaceutical Product Development LLC

Responsibilities

Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology, Serology/endocrinology, sample management

Name

PPD Development LP

Responsibilities

Multiple operational sponsor duties (codes present: 1,12,13,2,5,7,8,9)

Name

Fisher Clinical Services Pte Ltd / Fisher Clinical Services UK Limited / Fisher Clinical Services Inc.

Responsibilities

IP packaging/labeling and distribution

Name

QPS LLC

Responsibilities

VIR-2218 PK analysis

Third parties

• {"country":"United Kingdom","full_name":"The Doctors Laboratory Limited","duties_or_roles":"Serology/ endocrinology","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Australia","full_name":"Novotech (Australia) Pty Limited","duties_or_roles":"Sponsor duties codes: 1,10,12,13,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Singapore","full_name":"Fisher Clinical Services Pte Ltd","duties_or_roles":"IP pack/label & distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biomontr Labs","duties_or_roles":"HBV RNA analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"IP distirbution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"IP pack/label & distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"VIR-2218 PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"DDL Diagnostic Laboratory B.V.","duties_or_roles":"HBcrAg analysis, resistance surveillance analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"Sponsor duties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"VIR-2218 ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"anti-HBs analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"Pharmacovigilance services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellular Technology Ltd.","duties_or_roles":"PBMC analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Budget/contract negotiation; VIR-3434 PK analysis, VIR-3434 ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology, Serology/endocrinology, sample management","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"RNA-Seq analysis, Fc gamma receptor genotyping, immunoglobulin allotyping, HLA","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Multiple sponsor duties (codes present: 1,12,13,2,5,7,8,9)","organisation_type":"Pharmaceutical company"}