Phase 3 Multicenter Trial Comparing BJT-778 and Bulevirtide in Chronic Hepatitis D Infection Treatment

Trial ID: 2024-517167-23-00
Protocol: BJT-778-302
Sponsor: Mirum Pharmaceuticals Inc.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Hepatitis D

Objectives

The primary objective of this study is to evaluate the **efficacy** of brelovitug compared with bulevirtide (BLV) in the treatment of Chronic Hepatitis D Infection (CHD) at Week 48. This is clinically relevant as it aims to determine the potential of brelovitug as a more effective treatment option for CHD, which is a severe form of viral hepatitis with limited therapeutic options.

Secondary objectives include:

To evaluate the **safety** and tolerability of chronic treatment with brelovitug compared to BLV.
To characterize the **efficacy** of chronic treatment with brelovitug compared to BLV on Hepatitis Delta Virus (HDV).
To characterize the effect of chronic treatment with brelovitug compared to BLV on HDV disease progression, including assessment of HDV-related liver disease progression.
To evaluate the efficacy of switching from BLV to brelovitug (Arm 2).
To evaluate the safety and tolerability of switching from BLV to brelovitug (Arm 2).
To assess and compare to BLV the effect of brelovitug on Health-Related Quality of Life (HRQoL).

Participants

The clinical trial involves a total of **31 participants** diagnosed with **Chronic Hepatitis D Infection**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their ability to provide written informed consent and confirmation of chronic HDV infection, with specific criteria such as a positive anti-HDV antibody test or HDV RNA present for at least six months prior to the study. The trial does not include a vulnerable population. Participants are required to have an HDV RNA level greater than 500 IU/mL and elevated ALT levels at screening. Additionally, they must 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 specify any particular lifestyle considerations such as diet or physical activity.

Plans and Procedures

The clinical trial is a **randomized**, open-label, multicenter Phase 3 study designed to evaluate the efficacy of BJT-778 compared to **bulevirtide** for the treatment of **Chronic Hepatitis D Infection**. The trial aims to assess the primary endpoint of achieving a composite outcome of undetectable HDV RNA and ALT normalization at Week 48. The study will involve participants who meet specific inclusion criteria, such as being 18 years or older, having confirmed chronic HDV infection, and elevated ALT levels at screening. Participants must also be on or willing to take tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or entecavir at baseline and remain on stable treatment throughout the study.

The trial is expected to last until August 31, 2028, with recruitment starting on July 1, 2025. Participants will be involved in the study for a maximum treatment period of 96 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The follow-up visits will occur at Weeks 24, 48, 72, and 96, with assessments including liver stiffness, ALT levels, and HDV RNA levels. The study will also evaluate secondary endpoints such as the incidence of treatment-emergent adverse events and changes in liver disease progression.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial will be conducted under strict ethical guidelines, ensuring the safety and well-being of all participants. The study's design and methodology are structured to provide robust data on the comparative efficacy and safety of BJT-778 and bulevirtide, contributing valuable insights into the management of Chronic Hepatitis D Infection.

Treatment

The clinical trial involves the evaluation of two treatments for **Chronic Hepatitis Delta Infection**. The experimental medication, **BJT-778**, is a **solution for injection** developed by Bluejay Therapeutics, Inc. It is administered via **subcutaneous injection**. The maximum daily dose of BJT-778 is 300 mg, with a total maximum dose of 28,800 mg over a treatment period of 96 weeks. The active substance, BJT-778, is of protein origin and is not formulated for pediatric use. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The comparator treatment in this trial is **Bulevirtide**, also a **solution for injection**. Bulevirtide is administered through **subcutaneous injection** with a maximum daily dose of 2 mg and a total maximum dose of 672 mg over a 48-week treatment period. Like BJT-778, Bulevirtide is of protein origin and is not intended for pediatric use. The trial aims to compare the efficacy of BJT-778 against Bulevirtide, with participant adherence to the dosing schedule being closely monitored to maintain the integrity of the study results.

Efficacy

The efficacy of the investigational product BJT-778 will be assessed in a Phase 3 clinical trial comparing it to Bulevirtide for the treatment of **Chronic Hepatitis Delta** infection. The primary endpoint for evaluating efficacy is the proportion of participants achieving a composite endpoint, which includes undetectable HDV RNA and ALT normalization. Undetectable HDV RNA is defined as HDV RNA below the lower limit of quantification, with the target not detected, while ALT normalization is defined as a decrease in ALT from baseline to levels at or below the upper limit of normal.

Secondary endpoints will further assess efficacy through various measures, including the incidence and severity of treatment-emergent adverse events, the proportion of participants achieving the composite endpoint during treatment, and changes in liver stiffness as determined by transient elastography at Weeks 24, 48, and 96. Additional secondary endpoints include changes in the AST-to-platelet ratio index (APRI), CTP score, and Model for End-Stage Liver Disease (MELD) score at specified time points, as well as the proportion of participants with clinical disease progression. Patient-reported outcomes will be evaluated using the Chronic Liver Disease Questionnaire-HBV and the Functional Assessment of Chronic Illness Therapy – Fatigue at Weeks 24, 48, and 96.

Inclusion and Exclusion Criteria

check_circle

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 a positive for anti-HDV antibody test or HDV RNA 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.

cancel

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 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 (Class B or C) (see Section 6.7.7.2)
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 hepatitis A virus) 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 has resolved or been successfully treated (HCV RNA negative ≥6 months) prior to Screening.
Uncontrolled 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 or bulevirtide 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 Cockcroft-Gault (CLCr) <50 mL/min d) Alpha fetoprotein >100 ng/mL
Treatment with an investigational drug, a biological agent, or device within 4 weeks of baseline or 5 half-lives, whichever is longer
Received bulevirtide at any time prior to Screening, or unwilling or unable to receive bulevirtide treatment.
Unwilling or unable to self-inject study medication, including daily injection with bulevirtide
Use of any prohibited concomitant medications, including any interferon within 12 weeks prior to Screening, as described in Section 7.8, or described in the Hepcludex SmPC/Product Information
Regular alcohol misuse, defined as weekly intake of ≥14 drinks per week (average of ≥2 drinks per day) within 12 months of Screening
Clinically relevant drug abuse (excluding 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

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Recruiting	01 Jul 2025	5
Czechia	Recruiting	01 Jul 2025	17
France	Recruiting	01 Jul 2025	25
Germany	Recruiting	01 Jul 2025	14
Italy	Recruiting	01 Jul 2025	22
Romania	Recruiting	01 Jul 2025	20
Spain	Recruiting	01 Jul 2025	35
Sweden	Recruiting	01 Jul 2025	3