A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of BJT-778 in Subjects with Chronic HBV Infection (CHB) and Chronic HDV Infection (CHD).
A Phase 1/2a, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of BJT-778 in Healthy Volunteers and in Subjects with Chronic Hepatitis B Infection, Including Subjects with Chronic Hepatitis D Infection - Part 3 conducted in individuals with chronic hepatitis B and D co-infection.
Bluejay Therapeutics Inc.
72 participants
May 20, 2023
Interventional
Conditions
Summary
Hepatitis B virus (HBV) infection is one of the most common infectious diseases in the world, with nearly 300 million people chronically infected worldwide. Chronic HBV infection can lead to serious complications such as cirrhosis, liver failure, hepatocellular carcinoma (HCC), and death. Approximately 820,000 people die every year due to consequences of CHB. Hepatitis delta virus (HDV) is the causative agent of chronic hepatitis delta (CHD), the most severe form of viral hepatitis. Infection with HDV is dependent on the presence of HBV infection, as it uses HBV encoded envelope proteins (HBsAg) for infection and replication HDV infection can occur either simultaneously with HBV or, more commonly, as a superinfection in patients already chronically infected with HBV. Relative to CHB infection alone, CHD co-infection is associated with more severe liver disease, causing faster progression to cirrhosis, hepatocellular carcinoma, and liver failure. Developing therapeutic strategies that deplete HBsAg levels, like monoclonal antibodies, may play a role in future regimens targeting functional cure. There is a clear need for additional treatment for CHD, particularly agents that improve response rates, are better tolerated, and simpler to administer than currently available treatments. BlueJay Therapeutics has developed BJT-778, which has the potential to provide anti HBV and anti HDV benefits by neutralizing and clearing HBV and HDV virions as well as by depleting HBsAg containing subviral particles, which may help reconstitute HBV-specific immunity and contribute to functional cure for CHB. BJT-778 is a potent, selective neutralizing monoclonal antibody for the treatment of CHB and CHD. This study will evaluate the safety, tolerability, pharmacokinetics and antiviral activity of BJT-778 in participants with Chronic HBV Infection (CHB) and Chronic HDV Infection (CHD).
Eligibility
Inclusion Criteria11
- Able and willing to provide written informed consent (signed and dated) and any authorizations required by local law and can comply with all study requirements
- Male or female adults between 18 and 70 years of age
- BMI 18-40 kg/m2
- Chronic HBV infection greater than or equal to 6 months (e.g., positive for serum HBsAg greater than or equal to 6 months)
- Plasma HBV DNA less than 100 IU/ml at Screening
- On nucleos(t)ide analogs
- Qualitative HBsAg level criteria at Screening by Cohort/group:
- Cohort D and F: greater than or equal to 10 IU/ml
- Females: Non-pregnant and non-lactating; surgically sterile, post-menopausal or, if engaged in sexual relations of childbearing potential, subject is using an acceptable contraceptive method from the time of signing the informed consent form until at least 12 weeks after the last dose of Study Drug.
- Males: Surgically sterile or if engaged in sexual relations with a female of child-bearing potential, subject is utilizing an acceptable contraceptive method during treatment with Study Drug and for at least 12 weeks after the last dose of Study Drug. Agree not to donate sperm for at least 12 weeks after the last dose of Study Drug.
- Must have quantifiable serum HDV RNA levels at screening
Exclusion Criteria15
- Evidence of cirrhosis
- History of decompensated liver disease as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices
- History of liver disease other than Hepatitis B (i.e., NASH, alcohol associated hepatitis, cholestatic liver disease, etc.)
- Chronic hepatitis C virus (HCV) infection; subjects with past HCV RNA infection that was successfully treated must be HCV RNA negative and at least 24 weeks post treatment.
- Received solid organ or bone marrow transplant
- Currently taking, or took within 1 month of Screening, any immunosuppressing drugs (e.g., prednisone). If the subject received a short course, the situation may be discussed with the Medical Monitor, or designee
- Clinically significant abnormalities aside from chronic HBV infection in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening, uncontrolled diabetes) or physical examination
- History of bleeding diathesis or coagulopathy
- History of, or suspected presence of vasculitis
- History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa)
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- Treatment with a different investigational drug other than BJT-778, biological agent, or device within 4 weeks of screening or 5 half-lives of Study Drug, whichever is longer.
- History of drug abuse/addiction within 6 months (except cannabis) of Screening or positive urine drug Screen (excluding physician-prescribed drugs and cannabis)
- Unwillingness to comply with study procedures, including follow-up, 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 subject unsuitable for inclusion or could interfere with the subject participating in or completing the study.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
BJT-778 is being developed as a potent, selective neutralizing monoclonal antibody for the treatment of Chronic Hepatitis B Virus Infection (CHB) and Chronic Hepatitis D Virus Infection (CHD). Cohort D: Dosing of Groups D1 (Dose 1) may initiate when the Dose 1 is deemed safe in healthy volunteers (Group A1) by the Safety Review Committee (SRC) at the Day 14 safety review. Dose escalation to Dose 2 (Group D2) may proceed when the Day 14 safety review of the healthy volunteers at the Dose 2 (Group A2) and the Dose 1 in HBV-infected subjects (all participants from B1, and enrolled participants from D1) have determined to have acceptable safety profiles. The SRC will also incorporate available longer-term safety, efficacy, and PK data from all current and prior dosing groups into the decision making. Dose escalation to the optional Dose 3 in each group (B3, C3 and D3) may proceed once at least 14-day safety is established in the healthy volunteers at Dose 3 (Group A3) and 14-day safety is established at Dose 3 of the respective cohorts (B2, C2, and D2) per SRC review. Subjects will be monitored with serial vitals, ECGs, safety laboratory assessments, and AEs recording. Cohort D all will receive open-label BJT-778 and target 4 subjects per dose. Cohort D: CHB+CHD coinfection: • D1) Dose 1 ×1 subcutaneously (SC) • D2) Dose 2 ×1 SC • D3) Optional Dose 3 ×1 SC Cohort F: Once the safety and antiviral activity in Cohort D are established for a given dose (i.e., Dose 1), optional open-label multidose BJT-778 cohorts may be initiated and at different dosing intervals (i.e., every1, 2 or 4 weeks). The decision to initiate multidose cohorts for a given dose (i.e., Dose 1) will be determined by safety and maximum HDV RNA reductions observed with a single dose. Approximately 10 subject per cohort, this may be expanded to 20 subjects per cohort will be enrolled in Cohort F. For a given dose (i.e., Dose 1), cohorts exploring different intervals may enroll simultaneously or sequentially at the discretion of the Sponsor. • F1) Optional Dose considered safe in Cohort D, given subcutaneously at a TBD interval for 12 weeks • F2) Optional Dose considered safe in Cohort D, given subcutaneously at a TBD interval for 12 weeks • F3) 900mg SC at week 0, 2 and 4, then every 4 weeks up to week 48 All Subjects will continue their nucleos(t)ide treatment for the duration of the study including the follow up. Doses fall within the range of 75mg to 900mg and the exact doses will be disclosed after IP restrictions are met.
Locations(9)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12623000105640