A Phase 2 Study to Evaluate Efficacy, Safety and Tolerability of VIR-2218 and VIR-3434 in Participants with Chronic Hepatitis D Virus Infection (SOLSTICE)
- Conditions
- Chronic Hepatitis D Virus (HDV) InfectionHepatitis D10047438
- Registration Number
- NL-OMON53856
- Lead Sponsor
- Vir Biotechnology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
Age 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) and aspartate
aminotransferase (AST) > 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 48
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 48 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 48 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
Other Inclusion Criteria 11. 12-lead electrocardiogram (ECG) within normal
limits; or, with no clinically significant abnormalities at screening, as
determined by the investigator. 12. Agrees not to donate blood during the
duration of the study and for an additional 3 months after the last dose of
study intervention. Cohort Specific Inclusion Criteria 13. Cohort 1 specific
inclusion criteria • Noncirrhotic * Liver biopsy with METAVIR F0-F3 or Liver
elastography (eg, Fibroscan®) < 12 kilopascal (kPa) within the 12 months prior
to screening * Creatinine clearance (CLcr) >= 30 mL/min as calculated by the
Cockcroft-Gault formula at screening * Platelet count > 150,000 cells/mm3 (/µL)
• Cirrhotic * Liver biopsy with METAVIR F4 or Liver elastography (Fibroscan®) >=
12 kPa (Cohort 2) within the 12 months prior to screening * CLcr >= 60 mL/min as
calculated by the Cockcroft
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 >= 5x 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 are not eligible. Participants who are asymptomatic and
HAV or HEV immunoglobulin G antibody (IgG) positive are eligible. 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. Prior/Concomitant
Therapy 21. Therapy with an immunomodulatory agent, IFN-a (eg, IFN-alfa-2a or
IFN-alfa-2b, or pegylated IFN-alfa-2a or alfa 2b), immunosuppressants (eg,
disease-modifying antirheumatic drugs), cytotoxic or chemotherapeutic agent, or
chronic systemic corticosteroids within 6 months of screening. 22. Received an
HDV active agent (including lonafarnib and bulevirtide) within 90 days or 5
half-lives (if known), whichever is longer, before study drug administration or
are active in the Follow-Up period 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. 23. Receipt of an oligonucleotide
(eg, siRNA, antisense oligonucleotide) with activity against HBV within 48
weeks before study drug administration 24. Receipt of VIR-3434 or any antibody
targeting HBV or
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoints<br /><br>- Proportion of participants with undetectable HDV RNA (< LOD) or >= 2 log10<br /><br>decrease in HDV RNA from baseline and alanine aminotransferase (ALT)<br /><br>normalization (ALT < upper limit of normal [ULN]) at Week 24 (Cohorts 2 and 3<br /><br>only)<br /><br>- Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)</p><br>
- Secondary Outcome Measures
Name Time Method