Chronic Hepatitis D
Conditions
Brief summary
This is a Phase 2b/3, randomized, open-label, multicenter trial evaluating the efficacy and safety of switching from bulevirtide to brelovitug for the treatment of chronic hepatitis Delta infection (CHD).
Detailed description
This is a Phase 2b/3, open-label, multicenter study evaluating the efficacy and safety of switching participants on bulevirtide to brelovitug for the treatment of chronic hepatitis delta (CHD).
Interventions
DRUGBrelovitug (BJT-778)
Brelovitug (BJT-778), 300 mg administered subcutaneously once weekly for 96 weeks.
DRUGBulevirtide
Bulevirtide - once daily. Brelovitug (BJT-778) - 300 mg once weekly for 72 weeks following bulevirtide.
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent. 2. Male or female, ≥18 years of age at Screening. 3. Taking or willing to take TDF, TAF, or ETV at baseline, and willing to remain on stable treatment for the duration of the study. 4. Currently taking bulevirtide treatment for CHD for ≥6 months at the time of Screening. 5. HDV RNA ≥100 IU/mL at Screening.
Exclusion criteria
1. Evidence of decompensated liver disease (e.g., CTP Class B or C, history of hepatic encephalopathy, clinically significant ascites, or variceal bleeding). 2. Known history of immune-complex disease. 3. Active or clinically significant co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV). 4. Evidence of other significant liver diseases (e.g., autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis). 5. History of hepatocellular carcinoma (HCC) or evidence of HCC on screening imaging.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with undetectable HDV RNA (<LLOQ Target not detected [TND]) | Week 24 | The proportion of participants with undetectable HDV RNA (\<LLOQ, TND) at Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Up to Week 96 | Incidence and severity of treatment-emergent adverse events (TEAEs) during brelovitug and bulevirtide treatment periods. |
| Proportion of participants who permanently discontinue treatment due to an adverse event | Up to Week 96 | Proportion of participants who permanently discontinue study treatment because of an adverse event. |
| Change from baseline in serum total bile salts | Up to Week 96 | Mean change from baseline in serum total bile salt levels. |
| Proportion of participants achieving virologic response (HDV RNA ≥2 log10 IU/mL decline from baseline or HDV RNA <LLOQ, TND) | Up to Week 96 | Proportion of participants with virologic response at Weeks 24, 48, 72, and 96. |
| Proportion of participants achieving HDV RNA < LLOQ at Weeks 24, 48, 72 and 96. | Up to Week 96 | — |
| Proportion of participants achieving HDV RNA (HDV RNA < LLOQ, TND) at Weeks 48, 72, and 96. | Up to Week 96 | — |
| Proportion of participants achieving normal ALT at Weeks 24, 48, 72 and 96. | Up to Week 96 | — |
| Proportion of participants achieving normal ALT with virologic response (HDV RNA ≥2 log10 IU/mL decline from baseline or HDV RNA <LLOQ, TND) | Up to Week 96 | Proportion of participants with normal ALT and virologic response at Weeks 24, 48, 72, and 96. |
| Proportion of participants achieving normal ALT with HDV RDA < LLOQ at Weeks 24, 48, 72 and 96. | Up to Week 96 | — |
| Proportion of participants achieving normal ALT with HDV RNA (HDV RNA < LLOQ, TND) at Weeks 24, 48, 72 and 96 | Up to Week 96 | — |
| Change from baseline in HDV RNA | Up to Week 96 | Change from baseline in HDV RNA levels over time during treatment. |
| Change from baseline in ALT levels | Up to Week 96 | Change from baseline ALT levels over time during treatment. |
| Change from baseline in liver stiffness | Up to Week 96 | Change from baseline in liver stiffness as determined by transient elastography at weeks 24, 48 and 96 |
| Change from baseline in APRI | Up to Week 96 | Change from baseline in APRI at weeks 24, 48, and 96 |
| Change in baseline in CTP score | Up to Week 96 | Change from baseline in CTP score at Weeks 24, 48, and 96 in participants with cirrhosis |
| Change from baseline in MELD score | Up to Week 96 | Change from baseline in MELD score at Weeks 24, 48, and 96 in participants with cirrhosis |
| Proportion of participants with clinical disease progression from baseline | Up to Week 96 | Proportion of participants with clinical disease progression from baseline in HDV-associated liver disease at Weeks 24, 48, and 96. |
| Proportion of participants who achieve HDV RNA < LLOQ, TND at post-treatment follow-up | Up to Week 48 | — |
Countries
Austria, Czechia, France, Germany, Italy, Romania, Spain, United Kingdom
Contacts
CONTACTClinical Trials Mirum
CONTACTMedinfo Mirum
Outcome results
None listed