Hepatitis D, Chronic
Conditions
Keywords
HDV, Hepatitis D Virus, Hepatitis, Chronic Hepatitis D Virus, Hepatitis Delta Virus
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
Detailed description
Participants may be enrolled into Cohort 1 (1a and 1b) or Cohort 2 (2a, 2b1 or 2b2, 2c), 3, 4, and 5. All participants still receiving VIR-2218 or VIR-3434 monotherapy at the time of implementation of Protocol Amendment 4 will switch to combination therapy at Week 132 (Cohort 2a, 2b1/2b2) or Week 112 (Cohort 3).
Interventions
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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 * 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. * Anti-HBs \>10 mIU/mL at screening
Design outcomes
Primary
| 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 | Up to 24 Weeks |
| Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Up to 118 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Proportion of participants with ALT normalization 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) 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 | — |
| Change from baseline in liver fibrosis at Week 48, Week 96, Week 144, and Week 192 | Up to 192 Weeks. | Liver Fibrosis will be measured by conventional Transient Elastography imaging technique reported in kPa. |
| 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 | Up to 192 Weeks | MELD score will be calculated using serum bilirubin, serum creatinine, and International Normalized Ratio. |
| Change from baseline in Child-Pugh-Turcotte (CPT) score at Week 24, Week 48, Week 72, Week 96, Week 144, and Week 192 | Up to 192 Weeks | — |
| Incidence of anti-drug antibodies (ADA) and titers of ADA to VIR-3434 at specified study visits up to Week 192 (for cohorts with VIR3434) | 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 | — |
Countries
Bulgaria, France, Germany, Italy, Moldova, Netherlands, New Zealand, Romania, United Kingdom
Outcome results
None listed