SOLSTICE: Combination Therapy for the Treatment of Chronic Hepatitis D 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)

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

Study Overview

• Status: Recruiting
• Conditions: Hepatitis D, Chronic
• Intervention / Treatment: Drug: VIR-2218; Drug: VIR-3434; Drug: NRTI

Detailed Description

Participants may be enrolled into Cohort 1 (1a and 1b) or Cohort 2 (2a, 2b1 or 2b2, 2c), 3, and 4.

• Study Type: Interventional
• Enrollment (Estimated): 118
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Inquiry; Phone Number: 415-654-5281; Email: clinicaltrials@vir.bio

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1407
    • Not yet recruiting
    • Investigative Site
  • Sofia, Bulgaria, 1431
    • Recruiting
    • Investigative Site
  • Stara Zagora, Bulgaria, 6003
    • Recruiting
    • Investigative Site
• France
  • Clichy, France, 92110
    • Not yet recruiting
    • Investigative Site
  • Pessac, France, 33600
    • Not yet recruiting
    • Investigative Site
  • Rennes, France, 35000
    • Not yet recruiting
    • Investigative Site
  • Toulouse, France, 31000
    • Not yet recruiting
    • Investigative Site
• Germany
  • Frankfurt, Germany, 60596
    • Recruiting
    • Investigative Site
  • Hannover, Germany, 30625
    • Recruiting
    • Investigative Site
  • Mainz, Germany, 55131
    • Not yet recruiting
    • Investigative Site
  • Tübingen, Germany, 72076
    • Not yet recruiting
    • Investigative Site
• Italy
  • Milano, Italy, 20122
    • Recruiting
    • Investigative Site
  • Pisa, Italy, 56124
    • Recruiting
    • Investigative Site
  • Torino, Italy, 10126
    • Not yet recruiting
    • Investigative Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Recruiting
    • Investigative Site
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Investigative Site
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • Investigative Site
• Romania
  • Bucharest, Romania, 021105
    • Recruiting
    • Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Recruiting
    • Investigative Site
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Investigative Site
  • London, United Kingdom, E1 1RF
    • Recruiting
    • Investigative Site
  • Manchester, United Kingdom, M8 5RB
    • Recruiting
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Anti-HBs >10 mIU/mL at screening if only adding a select set of EC
• Non-cirrhotic and CPT-A cirrhotic

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a (VIR-2218); Participants will receive multiple doses of VIR-2218 for up to 96 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection
Experimental: Cohort 1b (VIR-3434); Participants will receive multiple doses of VIR-3434 for up to 96 weeks total.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 2a (VIR-2218); Participants will receive multiple doses of VIR-2218 for 96 weeks.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection
Experimental: Cohort 2b1 (VIR-3434); Participants will receive multiple doses of VIR-3434 for 96 weeks.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 2b2 (VIR-3434); Participants will receive multiple doses of VIR-3434 for 96 weeks.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 2c (VIR-2218 + VIR-3434); Participants will receive multiple doses of VIR-2218 + VIR-3434 for 96 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 3 (VIR-3434); Participants will receive multiple doses of VIR-3434 for 48 or 96 weeks.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Placebo Comparator: Cohort 4 (NRTI); Participants will receive NRTI for 12 weeks, then assign to Cohort 2c or Cohort 3.	Drug: NRTI; NRTI given orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 (Cohorts 2 and 3 only)	Up to 24 Weeks
Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Up to 118 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with HDV RNA < lower limit of quantitation (LLOQ) at Week 12, Week 24, Week 48, Week 72, and Week 96		Up to 96 Weeks
Change from baseline in HDV RNA at Week 12, Week 24, Week 48, Week 72, and Week 96		Up to 96 Weeks
Proportion of participants with ALT normalization at Week 12, Week 24, Week 48, Week 72, and Week 96		Up to 96 Weeks
Incidence of anti-drug antibodies (ADA) and titers of ADA to VIR-3434 at each study visit up to Week 96 (for cohorts with VIR-3434)		Up to 96 Weeks
Change from baseline in liver fibrosis at Week 48 and Week 96	Liver Fibrosis will be measured by conventional Transient Elastography imaging technique reported in kPa.	Up to 96 Weeks.
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, and Week 96	MELD score will be calculated using serum bilirubin, serum creatinine, and International Normalized Ratio.	Up to 96 Weeks
Change from baseline in Child-Pugh-Turcotte (CPT) score at Week 24, Week 48, Week 72, and Week 96		Up to 96 Weeks
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, and Week 96		Up to 96 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, and Week 96		Up to 96 Weeks
Proportion of participants with undetectable HDV RNA (less than LOD) at Week 12, Week 24, Week 48, Week 72, and Week 96		Up to 96 Weeks

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Hepatitis; HDV; Hepatitis D Virus; Chronic Hepatitis D Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis; Hepatitis A; Hepatitis D; Hepatitis D, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: VIR-CHDV-V201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes