SOLSTICE: Combination Therapy for the Treatment of Chronic Hepatitis D Infection.

NCT05461170 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: VIR-CHDV-V201
• Study Type: interventional
• Target: 95
• Locations: 9 countries
• Sites: 20

Brief Summary

This is a phase 2 trial in which participants with chronic hepatitis D virus (HDV) infection will receive VIR-2218 and/or VIR-3434 and be assessed for safety, tolerability, and efficacy

Conditions

Hepatitis D, Chronic

Keywords

HDV; Hepatitis D Virus; Hepatitis; Chronic Hepatitis D Virus; Hepatitis Delta Virus

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with undetectable HDV RNA (< limit of detection [LOD]) or ≥ 2 log10 decrease in HDV RNA from baseline and alanine aminotransferase (ALT) normalization (ALT < upper limit of normal [ULN]) at Week 24

  Up to 24 Weeks

• Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

  Up to 118 Weeks

Secondary Outcomes (10)

• Proportion of participants with undetectable HDV RNA (less than LOD) or greater than/equal to 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.

  Up to 192 Weeks

• Proportion of participants with undetectable HDV RNA (less than LOD) or greater than/equal to 2 log10 decrease in HDV RNA from baseline at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.

  Up to 192 Weeks

• Proportion of participants with undetectable HDV RNA (less than LOD) at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.

  Up to 192 Weeks

• 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.

  Up to 192 Weeks

• Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192.

  Up to 192 Weeks

Study Arms (9)

Cohort 1a (VIR-2218)

EXPERIMENTAL

Participants will receive multiple doses of VIR-2218 for up to 96 weeks total.

Drug: VIR-2218

Cohort 1b (VIR-3434)

EXPERIMENTAL

Participants will receive multiple doses of VIR-3434 for up to 96 weeks total.

Drug: VIR-3434

Cohort 2a (VIR-2218)

EXPERIMENTAL

Participants will receive multiple doses of VIR-2218 for up to 132 weeks, then assign to Cohort 2c.

Drug: VIR-2218

Cohort 2b1 (VIR-3434)

EXPERIMENTAL

Participants will receive multiple doses of VIR-3434 for up to 132 weeks, then assign to Cohort 2c.

Drug: VIR-3434

Cohort 2b2 (VIR-3434)

EXPERIMENTAL

Participants will receive multiple doses of VIR-3434 for up to 132 weeks, then assign to Cohort 2c.

Drug: VIR-3434

Cohort 2c (VIR-2218 + VIR-3434)

EXPERIMENTAL

Participants will receive multiple doses of VIR-2218 + VIR-3434 for up to 192 weeks.

Drug: VIR-2218; Drug: VIR-3434

Cohort 3 (VIR-3434)

EXPERIMENTAL

Participants will receive multiple doses of VIR-3434 for up to 112 weeks, then assign to Cohort 2c.

Drug: VIR-3434

Cohort 4 (NRTI)

PLACEBO COMPARATOR

Participants will receive NRTI for 12 weeks, then assign to Cohort 2c or Cohort 3.

Drug: NRTI

Cohort 5 (VIR-2218)

EXPERIMENTAL

Participants will receive multiple doses of VIR-2218 for 12 weeks, then assign to Cohort 2c.

Drug: VIR-2218

Interventions

VIR-2218 DRUG

VIR-2218 given by subcutaneous injection

Also known as: Elebsiran

Cohort 1a (VIR-2218); Cohort 2a (VIR-2218); Cohort 2c (VIR-2218 + VIR-3434); Cohort 5 (VIR-2218)

VIR-3434 DRUG

VIR-3434 given by subcutaneous injection

Also known as: Tobevibart

Cohort 1b (VIR-3434); Cohort 2b1 (VIR-3434); Cohort 2b2 (VIR-3434); Cohort 2c (VIR-2218 + VIR-3434); Cohort 3 (VIR-3434)

NRTI DRUG

NRTI given orally.

Cohort 4 (NRTI)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ages 18 to \< 70 years at screening
• Chronic HDV infection for \>/= 6 months
• On NRTI therapy for at least 12 weeks prior to day 1
• ALT\>ULN and \< 5x ULN
• Non-cirrhotic and CPT-A cirrhotic

You may not qualify if:

• Any clinically significant chronic or acute medical or psychiatric condition that makes the participant unsuitable for participation.
• History of significant liver disease from non-HBV or non-HDV etiology
• History of allergic reactions, hypersensitivity, or intolerance to study drug, its metabolites, or excipients.
• History of anaphylaxis
• History of immune complex disease
• History of autoimmune disorder
• History or evidence of alcohol or drug abuse
• Prior or concomitant therapy with an immunomodulatory agent, IFN-alpha, cytotoxic or chemotherapeutic agent, or chronic corticosteroids.
• Anti-HBs \>10 mIU/mL at screening

Sponsors & Collaborators

• Vir Biotechnology, Inc.: lead

Study Sites (20)

Investigative Site

Sofia, 1407, Bulgaria

Location

Investigative Site

Sofia, 1431, Bulgaria

Location

Investigative Site

Stara Zagora, 6003, Bulgaria

Location

Investigative Site

Clichy, 92110, France

Location

Investigative Site

Pessac, 33600, France

Location

Investigative Site

Rennes, 35000, France

Location

Investigative Site

Toulouse, 31000, France

Location

Investigative Site

Frankfurt, 60596, Germany

Location

Investigative Site

Hanover, 30625, Germany

Location

Investigative Site

Tübingen, 72076, Germany

Location

Investigative Site

Milan, 20122, Italy

Location

Investigative Site

Pisa, 56124, Italy

Location

Investigative Site

Chisinau, MD-2025, Moldova

Location

Investigative Site

Rotterdam, 3015 GD, Netherlands

Location

Investigative Site

Auckland, 1010, New Zealand

Location

Investigative Site

Bucharest, 021105, Romania

Location

Investigative Site

Birmingham, B15 2TT, United Kingdom

Location

Investigative Site

London, E1 1RF, United Kingdom

Location

Investigative Site

London, SE5 9RS, United Kingdom

Location

Investigative Site

Manchester, M8 5RB, United Kingdom

Location

Related Publications (1)

• Asselah T, Chattergoon MA, Jucov A, Streinu-Cercel A, Lampertico P, Wedemeyer H, Kennedy PT, Gane EJ, Bullard BL, Chow S, Santos D, Camus G, Lu Y, Pilowa C, Hwang C, Correll T, Agarwal K; SOLSTICE Trial Investigators. A Phase 2 Trial of Tobevibart plus Elebsiran in Hepatitis D. N Engl J Med. 2026 Jan 22;394(4):343-353. doi: 10.1056/NEJMoa2508827. Epub 2025 Nov 9.

  PMID: 41211943 DERIVED

MeSH Terms

Conditions

Hepatitis D, Chronic; Hepatitis; Hepatitis D

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 18, 2022
• Study Start: September 17, 2022
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: October 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (3); RO (1); DE (3); FR (4); MO (1); NZ (1); NL (1); IT (2); GB (4)