Evaluation of BJT-778 Versus Delayed Treatment in Chronic Hepatitis Delta Infection: A Global, Randomized, Open-label, Multicenter Phase 2b/3 Trial

Trial ID: 2024-519063-18-00
Protocol: BJT-778-301
Sponsor: Mirum Pharmaceuticals Inc.

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Diseases & Conditions

Hepatitis D

Objectives

The primary objective of this study is to evaluate the **efficacy** of brelovitug compared with delayed treatment in patients with **Chronic Hepatitis Delta Infection** (CHD) at Week 24. This assessment is clinically relevant as it aims to determine the potential of brelovitug to improve treatment outcomes in CHD, a condition associated with significant morbidity and mortality.

Secondary objectives include:

Evaluating the efficacy of brelovitug on CHD compared with a pre-specified performance goal of 40% at Week 24.
Assessing the safety and tolerability of chronic treatment with brelovitug compared to delayed treatment.
Characterizing the efficacy of chronic treatment with brelovitug compared to delayed treatment on Hepatitis Delta Virus (HDV).
Comparing the efficacy of chronic treatment with brelovitug 900 mg to a 300 mg treatment regimen.
Evaluating the effect of chronic treatment with brelovitug on HDV disease progression, including the assessment of HDV-related liver disease progression.

Participants

The clinical trial involves a total of **120 participants** diagnosed with **Chronic Hepatitis Delta Infection**. The study population includes both male and female subjects, aged 18 years and older, who are in general good health aside from their chronic infection. Participants were selected based on their willingness and ability to provide written informed consent, and they must have a confirmed chronic HDV infection, evidenced by a positive anti-HDV antibody test or HDV RNA for at least six months prior to the study's commencement. Additionally, participants are required to have an HDV RNA level greater than 500 IU/mL and elevated ALT levels at screening. They must also be taking or willing to take tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or entecavir at baseline and remain on stable treatment throughout the study. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

Plans and Procedures

The clinical trial is a **randomized**, open-label, multicenter, Phase 2b/3 study designed to evaluate the efficacy of BJT-778 compared to delayed treatment in patients with **Chronic Hepatitis Delta Infection**. The trial aims to assess the primary endpoint of virologic response and ALT normalization at Week 24. The study will involve the administration of BJT-778 as a **solution for injection** via **subcutaneous injection**. The trial is expected to commence recruitment on June 2, 2025, and conclude by June 30, 2029, with a maximum treatment period of 96 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmation of chronic HDV infection, and baseline HDV RNA and ALT levels. Following the screening, eligible participants will be randomized to receive either BJT-778 or delayed treatment. Study visits will occur at regular intervals to monitor safety and efficacy, including assessments of virologic response, ALT levels, and liver stiffness. The end-of-study visit will evaluate the overall outcomes and any long-term effects of the treatment.

The expected length of participant involvement is up to 96 weeks, with conditions for early termination including the occurrence of treatment-emergent adverse events or failure to adhere to the study protocol. Participants will be required to maintain stable treatment with tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or entecavir throughout the study. The trial will also assess secondary endpoints such as changes in liver stiffness, APRI, CTP, and MELD scores, as well as the incidence and severity of adverse events.

Treatment

The clinical trial involves the administration of **BJT-778**, an experimental medication developed by Bluejay Therapeutics, Inc. **BJT-778** is formulated as a **solution for injection** and is administered via **subcutaneous injection**. The active substance, also named **BJT-778**, is derived from a protein of other origin. The maximum daily dose of **BJT-778** is 900 mg, with a total maximum dose of 28,800 mg over a treatment period of up to 96 weeks. The medication is not a pediatric formulation and has been designated as an orphan drug, indicating its use in the treatment of a rare condition.

In this trial, **BJT-778** is being compared to a delayed treatment approach for the management of **chronic hepatitis delta infection**. The study is designed as a global, randomized, open-label, multicenter, Phase 2b/3 trial. The primary objective is to evaluate the efficacy of **BJT-778** compared to delayed treatment at Week 24. Participants' compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy

The efficacy of the investigational product BJT-778 in the treatment of **Chronic Hepatitis Delta** infection will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the proportion of participants achieving a composite endpoint of virologic response and alanine aminotransferase (ALT) normalization at Week 24. Virologic response is defined as a decrease in HDV RNA by at least 2 log10 IU/mL from baseline or undetectable HDV RNA levels. ALT normalization is characterized by a reduction in ALT levels to within the upper limit of normal (ULN).

Secondary endpoints will include the proportion of participants achieving the composite endpoint at Weeks 24, 48, and 96, as well as changes from baseline in liver stiffness, APRI, CTP score, and MELD score at specified time points. These assessments will be conducted using validated tools such as transient elastography (e.g., FibroScan). Additionally, the trial will evaluate the incidence and severity of treatment-emergent adverse events (TEAEs) and the proportion of participants who discontinue treatment due to adverse events. The efficacy parameters will be measured and analyzed according to a predefined schedule, with hierarchical testing applied to the primary efficacy analysis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Willing and able to provide written informed consent.
Male or female, ≥18 years of age at Screening.
Confirmation of chronic HDV infection, defined as positive for anti-HDV antibody test or HDV RNA for at least 6 months prior to Day 1. If prior documentation is not available, then HDV RNA positivity along with evidence of fibrosis (liver stiffness of ≥7 kPa) is acceptable.
HDV RNA >500 IU/mL at Screening.
ALT >ULN at Screening.
Taking or willing to take tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or entecavir (ETV) at baseline, and willing to remain on stable treatment for the duration of the study.

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Exclusion Criteria

Pregnant or nursing females.
Male or female participants of childbearing potential unwilling to comply with contraception requirements during the study.
Current, prior history, or is under evaluation for any of the following: a) Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy, b) Clinical hepatic decompensation (i.e., ascites, encephalopathy variceal hemorrhage). Incidental small ascites on imaging without other clinical symptoms/signs would not exclude the participants, c) Hepatocellular carcinoma; suspected HCC on ultrasound at Screening, d) Vasculitis, e) Extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa), f) Solid organ or bone marrow transplantation, g) Significant pulmonary disease (e.g., O2-dependent or forced expiratory volume 1 second (FEV1) ≤50% predicted value), h) Significant cardiac disease (e.g., history of myocardial infarctions within 6 months, any history of ventricular tachycardia, congestive heart failure, dilated cardiomyopathy with left ventricular ejection fraction <40%), i) Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening).
CTP >6 B or C.
Presence of other liver disease(s) (non-HBV/HDV), such as nonalcoholic steatohepatitis (NASH), alcohol associated hepatitis, cholestatic liver disease, other viral (e.g., HCV or HAV) or non-viral hepatitis that has the potential to impact interpretation of data. Exceptions to this criterion include fatty liver without any signs of steatohepatitis or past HCV infection that was successfully treated (HCV RNA negative) ≥6 months prior to Screening.
Uncontrolled human immunodeficiency virus (HIV) infection defined as having quantifiable HIV RNA levels in the blood at Screening.
History of hypersensitivity to any of the components in the brelovitug formulation.
Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a participant unsuitable for inclusion: a) Platelet count <50,000/mm3 b) Hemoglobin <10.0 g/dL, c) Creatinine clearance by Crockcroft-Gault (CrCl) <30 mL/min, d) Alpha fetoprotein (AFP) >100 ng/mL.
Treatment with another investigational drug, a biological agent, or device within 4 weeks or 5 half-lives, whichever is longer, of Baseline.
Use of any prohibited concomitant medications as described in Section 7.7.
Regular alcohol misuse, defined as weekly intake of ≥14 alcoholic drinks per week (average of ≥2 alcoholic drinks per day) within 12 months of Screening.
Clinically relevant drug abuse (not including cannabis) within 12 months of Screening.
Unwillingness to comply with study procedures as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
Have any other conditions (medical, social, psychiatric, or other), which in the opinion of the Investigator would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.