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

Study Overview
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Brief Summary
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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

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

Official Title
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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
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Hepatitis D, Chronic

Intervention / Treatment
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* Drug: VIR-2218
* Drug: VIR-3434
* Drug: NRTI


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDV, Hepatitis D Virus, Hepatitis, Chronic Hepatitis D Virus