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

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) - SOLSTICE

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-001993-78-DE

Enrollment

124

Registered

2022-10-27

Start date

2023-04-14

Completion date

Unknown

Last updated

2024-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis D Virus (HDV) Infection MedDRA version: 20.1 Level: PT Classification code 10019762 Term: Hepatitis D System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: LLT Classification code 10047455 Term: Viral hepatitis B without mention of hepatic coma, with hepatitis delta System Organ Class: 10021881 - Infections and infestations

Interventions

Product Name: Elebsiran Product Code: VIR-2218 Pharmaceutical Form: Solution for injection INN or Proposed INN: Not available Current Sponsor code: ALN-81890 or AD-81890 Other descriptive name: VIR-22

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Age 1. Age = 18 (or age of legal consent, whichever is older) to 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 150,000 cells/mm3 (/µL) 14. Cohorts 2a, 2b1, 2b2, 2c, 3 & 4 specific inclusion criteria • Noncirrhotic -Liver biopsy with METAVIR F0-F3 or Liver elastography (eg, Fibroscan®) 150,000 cells/mm3 (/µL) • CPT-A Cirrhotic -Liver biopsy with METAVIR F4 or Liver elastography (eg

Exclusion criteria

Exclusion criteria: 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 1.5 13. Hemoglobin 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 intervention 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 intervention administration 24. Receipt of VIR-3434 or any antibody targeting HBV or HDV within 24 weeks of first study intervention administration Additional Exclusions 25. History or clinical evidence of alcohol or drug abuse within the 12

Design outcomes

Primary

Measure	Time frame
Main Objective: -To evaluate the efficacy of VIR-2218 and VIR-3434 in participants with chronic HDV infection in Cohorts 2 and 3 only. -To evaluate the safety of VIR-2218 and VIR-3434 in participants with chronic HDV infection in each cohort.;Secondary Objective: -To evaluate the efficacy of VIR-2218 and VIR-3434 in participants with chronic HDV infection on HDV RNA and ALT normalization in each cohort. -To assess the immunogenicity of VIR-3434 (for cohorts with VIR-3434) -To assess the effects of VIR-2218 and VIR-3434 on liver fibrosis and hepatic function in each cohort.;Primary end point(s): • 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 (Cohort 2 and 3 only) • Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: • Week 24 • Total study duration (up to 214 weeks)	—

Measure

Time frame

Main Objective: -To evaluate the efficacy of VIR-2218 and VIR-3434 in participants with chronic HDV infection in Cohorts 2 and 3 only. -To evaluate the safety of VIR-2218 and VIR-3434 in participants with chronic HDV infection in each cohort.;Secondary Objective: -To evaluate the efficacy of VIR-2218 and VIR-3434 in participants with chronic HDV infection on HDV RNA and ALT normalization in each cohort. -To assess the immunogenicity of VIR-3434 (for cohorts with VIR-3434) -To assess the effects of VIR-2218 and VIR-3434 on liver fibrosis and hepatic function in each cohort.;Primary end point(s): • 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 (Cohort 2 and 3 only) • Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: • Week 24 • Total study duration (up to 214 weeks)

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Secondary

Measure	Time frame
Secondary end point(s): • 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 • 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 • Proportion of participants with undetectable HDV RNA (< LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • 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 • Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • Incidence of ADA and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR-3434) • Change from baseline in liver fibrosis at Week 48. Week 96, Week 144, and Week 192 • 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 • Change from baseline CPT score at Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192;Timepoint(s) of evaluation of this end point: Timepoints of each end point detailed in previous section (E.5.2).	—

Measure

Time frame

Secondary end point(s): • 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 • 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 • Proportion of participants with undetectable HDV RNA (< LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • 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 • Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192 • Incidence of ADA and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR-3434) • Change from baseline in liver fibrosis at Week 48. Week 96, Week 144, and Week 192 • 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 • Change from baseline CPT score at Week 24, Week 48, Week 72, Week 96, Week 144 and Week 192;Timepoint(s) of evaluation of this end point: Timepoints of each end point detailed in previous section (E.5.2).

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Countries

Bulgaria, France, Germany, Italy, Moldova, Republic of, Netherlands, New Zealand, Romania, United Kingdom

Contacts

Public ContactTracy Spaeth King

Pharmaceutical Product Development (PPD)

VIRSOLSTICE.sm@ppd.com+19105584938

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026