Chronic HBV infection. MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Code: VIR-2218
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ELEBSIRAN
Current Sponsor code: ALN-81890 or AD-81890
Other descriptive name: VIR-2218
Concentration unit: mg/ml
Sponsors
Vir Biotechnology, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 (or age of legal consent, whichever is older) to the lower limit of detection 7. Negative anti-HBs at screening 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 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. 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 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. 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. 11. Willing to comply with the study requirements and able to provide written informed consent 12. Cohort 2b only: Previously enrolled in Cohort 1d of the VIR-2218-1001 study and completed the Treatment Period Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 365 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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. 2. History of clinically significant liver disease from non-HBV etiology 3. History of hepatic decompensation, including ascites, hepatic encephalopathy, and/or esophageal or gastric varices 4. History of immune complex disease 5. History of an autoimmune disorder 6. History of HBV-related extrahepatic disease, including but not limited to HBV-related rash, arthritis, or glomerulonephritis 7. History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments or any excipients of VIR-3434 8. History of anaphylaxis 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. 10. History of bone marrow or solid organ transplant 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 12. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (subjects with HDV) Subjects who are HCV antibody or HDV antibody positive but have a documented negative HCV , RNA or HDV RNA, respectively, are eligble. 13. Creatinine clearance (CLcr) 3x ULN b. direct bilirubin or INR > ULN 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 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). 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 or other immunosuppressive agents d. Parts A, C and D only: theophylline e. Parts A, C and D only: methadone 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. 19. Receipt of an oligonucleotide with activity against HBV within 48 weeks before study drug administration 20. Receipt of VIR-2218 or VIR-3434 within 24 weeks prior to Day 1 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. 22. Parts A, C and D only: Known h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety and tolerability of regimens containing VIR-2218 +, VIR-3434, and/or PEG IFNa •To evaluate the efficacy of regimens containing VIR-2218 +, VIR-3434, and/or PEG-IFNa ;Secondary Objective: •To assess the effect of regimens containing VIR-2218 +, VIR-3434, and/or PEG-IFNa on serum hepatitis B surface antigen (HBsAg) •To assess the effect of regimens containing VIR-2218, VIR-3434, and/or PEG-IFNa on serum HBV DNA •For hepatitis B e antigen (HBeAg)-) positive subjects: to assess the effect of regimens containing VIR- 2218 +, VIR-3434, and/or PEG-IFNa on HBeAg and anti-HBe •To assess the effect of regimens containing VIR-2218, VIR-3434, and/or PEG-IFNa on anti-HBs •To characterize the pharmacokinetics (PK) of VIR-3434 (Parts A, B, C, and Cohort 1d only) •To assess the immunogenicity of VIR-3434 (Parts A, B, C, and Cohort 1d only) •To evaluate the proportion of subjects meeting criteria for nucleos(t)ide reverse transcriptase inhibitor (NRTI) discontinuation or retreatment ;Primary end point(s): • Proportion of subjects with treatment-emergent adverse events (TEAEs) • Proportion of subjects with serious adverse events (SAEs) • Proportion of subjects with HBsAg loss at end of treatment • Proportion of subjects with HBsAg loss at 24 weeks post-end of treatment ;Timepoint(s) of evaluation of this end point: Cohort 1a/2a/8a: up to 88 weeks Cohort 3a/4a: up to 72 weeks Cohort 5a/6a: up to 79 weeks Cohort 7a/1b: up to 112 weeks Cohort 1c: up to 92 weeks Cohort 2c: up to 116 weeks Cohort 2b: up to 88 weeks Cohort 2c: up to 116 weeks Cohorts 1d: up to 116 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects achieving functional cure (defined as undetectable HBsAg and sustained suppression of HBV DNA LLOQ] for = 24 weeks after discontinuation of all treatment, including NRTIs) • Proportion of subjects with serum HBsAg < 10 IU/mL at end of treatment • Proportion of subjects with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment • Absolute serum HBsAg and change from baseline across timepoints in the study • Nadir and maximum reduction of serum of HBsAg from baseline • Time to achieve nadir and maximum reduction of serum HBsAg from baseline • Time to achieve serum HBsAg loss • For HBeAg-positive subjects: proportion of subjects with HBeAg loss (undetectable HBeAg) and/or anti-Hbe seroconversion • For HBeAg-positive subjects: time to HBeAg loss (undetectable HBeAg) and/or anti-Hbe seroconversion • Proportion of subjects with anti-HBs seroconversion • VIR-3434 PK parameters • Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434 • Proportion of subjects meeting criteria for NRTI discontinuation • Proportion of subjects meeting criteria for NRTI retreatment ;Timepoint(s) of evaluation of this end point: Cohort 1a/2a/8a: up to 88 weeks Cohort 3a/4a: up to 72 weeks Cohort 5a/6a: up to 79 weeks Cohort 7a/1b: up to 112 weeks Cohort 1c: up to 92 weeks Cohort 2c: up to 116 weeks Cohort 2b: up to 88 weeks Cohort 2c: up to 116 weeks Cohorts 1d: up to 116 weeks | — |
Countries
Canada, Germany, Hong Kong, Korea, Republic of, Malaysia, Moldova, Republic of, New Zealand, Romania, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactBrittany Marrow
Pharmaceutical Product Development -PPD
Outcome results
None listed