Chronic Hepatitis D Infection
Conditions
Keywords
Hepatitis Delta virus, HDV, Hepatitis D infection, Hepatitis D virus
Brief summary
This is a Phase 3, global, randomized, open-label, multicenter trial designed to evaluate the safety and efficacy of chronic treatment with brelovitug (BJT-778) for chronic hepatitis delta virus (HDV) infection. The objective of this study is to test the safety and effectiveness of brelovitug compared to delayed treatment.
Detailed description
The study consists of 3 study arms. Approximately 80 participants will be randomized 2:1:1 to one of the following treatment arms: Arm 1: Participants will receive brelovitug 300 mg subcutaneously once weekly for 96 weeks. Arm 2: Participants will receive brelovitug 900 mg subcutaneously once every 4 weeks for 96 weeks. Arm 3: Participants will attend study clinic visits and delay treatment with brelovitug for 12 weeks. At Week 12, participants will receive brelovitug 300 mg subcutaneously once weekly for 96 weeks.
Interventions
Route of administration- Subcutaneous Injection
Route of administration- Subcutaneous Injection
Route of administration- Subcutaneous Injection
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent 2. Chronic HDV infection 3. HDV RNA \>500 IU/mL at Screening 4. ALT \>ULN at Screening 5. Willing to take or already taking HBV nucleos(t)ide therapy.
Exclusion criteria
1. Pregnant or nursing females 2. Unwilling to comply with contraception requirements during the study 3. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy 4. Clinical hepatic decompensation (i.e., ascites, encephalopathy variceal hemorrhage). 5. Solid organ or bone marrow transplantation 6. Presence of other liver disease(s) (non-HBV/HDV), such as metabolic dysfunction-associated steatohepatitis (MASH), alcohol associated hepatitis, cholestatic liver disease, hepatocellular carcinoma. Note - Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with a composite endpoint of virologic response and ALT normalization at Week 24 in brelovitug arms compared to response at Week 12 of delayed-treatment arm | Week 24 | The composite endpoint is defined as virologic response (HDV RNA ≥2 log10 IU/mL decrease from Baseline or undetectable HDV RNA (\< the lower limit of quantification \[LLOQ\], target not detected \[TND\]) and ALT normalization (decrease in ALT from baseline to ≤ upper limit of normal \[ULN\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with treatment-emergent adverse events (TEAEs) | Up to 96 weeks | An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening (e.g., medical history), worsens during the study (post-Baseline/ Day 1), regardless of the suspected cause of the event. |
| Percentage of participants who discontinue treatment due to an adverse event (AE) | Up to 96 weeks | An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening (e.g., medical history), worsens during the study (post-Baseline/ Day 1), regardless of the suspected cause of the event. |
| Percentage of participants with HDV RNA ≥ 2 log10 IU/mL decline from baseline or TND | Up to 96 Weeks | — |
| Percentage of participants with HDV RNA <LLOQ | Up to 96 Weeks | — |
| Percentage of participants with HDV RNA <LLOQ, TND | Up to 96 Weeks | — |
| Percentage of participants with ALT normalization | Up to 96 Weeks | ALT normalization is defined as a decrease in ALT from baseline to ≤ ULN |
| Percentage of participants with ALT normalization in combination with virologic response of HDV RNA ≥ 2 log10 IU/mL decline from baseline or <LLOQ, TND | Up to 96 Weeks | The composite of participants with ALT normalization (decrease in ALT from baseline to ≤ ULN) and virologic response of HDV RNA ≥ 2 log10 IU/mL decline from baseline or TND. |
| Percentage of participants with ALT normalization in combination with HDV RNA <LLOQ | Up to 96 Weeks | The composite of participants with ALT normalization (decrease in ALT from baseline to ≤ ULN) and virologic response of HDV RNA \<LLOQ |
| Percentage of participants with ALT normalization in combination with HDV RNA <LLOQ, TND | Up to 96 Weeks | The composite of participants with ALT normalization (decrease in ALT from baseline to ≤ ULN) and virologic response of HDV RNA \<LLOQ, TND. |
| Percentage of participants with HDV RNA <LLOQ, TND at post-treatment follow up. | Post-Treatment Weeks 24 and 48 | — |
| Change from baseline in liver stiffness as determined by transient elastography (e.g., FibroScan) | Up to 96 Weeks | — |
| Change from baseline in APRI (AST-to-platelet ratio index) | Up to 96 Weeks | — |
| Change from baseline in CTP score in participants with cirrhosis | Up to 96 Weeks | — |
| Change from baseline in Model for End-Stage Liver Disease (MELD) score in participants with cirrhosis | Up to 96 Weeks | — |
| Percentage of participants with clinical disease progression from baseline in HDV-associated liver disease. | Up to 96 Weeks | Liver disease progression will be determined by the Independent Data Monitoring Committee (IDMC). |
Countries
Belgium, Bulgaria, Georgia, Hungary, Israel, Pakistan, Taiwan, Ukraine, United States, Uzbekistan
Outcome results
None listed