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 evaluating brelovitug (BJT-778) vs bulevirtide for the treatment of chronic hepatitis delta infection (CHD). The main goal of this study is to test the effectiveness of brelovitug compared to bulevirtide as a long-term treatment in patients with chronic HDV infection.
Detailed description
Study consists of 2 arms. Approximately 172 participants will be randomized 3:1 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 bulevirtide 2 mg subcutaneously once daily for 48 weeks, followed by brelovitug 300 mg subcutaneously once weekly for the next 48 weeks.
Interventions
Route of administration- Subcutaneous Injection
DRUGBulevirtide 2 mg and Brelovitug - 300 mg
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
Key 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 neucleos(t)ide therapy. Key
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 nonalcoholic steatohepatitis (NASH), 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 | Week 48 | The composite endpoint is defined as virologic response (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 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 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. |
| 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). |
| Percentage of participants with HDV RNA <LLOQ, TND at post-treatment follow up. | Post-Treatment Weeks 24 and 48 | — |
| Change from baseline in Health-Related Quality of Life (HRQoL) as measured by the Chronic Liver Disease Questionnaire-HBV (CLDQ-HBV) | Up to 96 Weeks | — |
| Change from baseline in Health-Related Quality of Life (HRQoL) as measured by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | Up to 96 Weeks | — |
Countries
Austria, Czechia, France, Germany, Italy, Romania, Spain, Sweden, Switzerland, United Kingdom, Uzbekistan
Contacts
CONTACTClinical Trials Clinical Trials Mirum
CONTACTMirum Pharmaceuticals, Inc., Clinical Trials
Outcome results
None listed