None listed
Conditions
Brief 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 multiple doses of BJT-778 in participants with Chronic HBV Infection (CHB).
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 E: Once the safety and antiviral activity in Cohort B +/- C are established for a given dose (i.e., Dose 1), optional open-label multidose BJT-778 cohorts may be initiated including different dosing intervals (i.e., every 1, 2 or 4 weeks). The decision to initiate multidose cohorts for a given dose
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 E: Once the safety and antiviral activity in Cohort B +/- C are established for a given dose (i.e., Dose 1), optional open-label multidose BJT-778 cohorts may be initiated including different dosing intervals (i.e., every 1, 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 HBsAg reductions observed with a single dose. Subjects will be monitored with serial vitals, ECGs, safety laboratory assessments, and AEs recording. The number of subjects per cohort in Cohort E is targeted at 8 but may be expanded to enable all qualifying subjects in Cohort B and C the opportunity to enroll. For a given dose (i.e., Dose 1), arms exploring different intervals may enroll simultaneously or sequentially at the discretion of the Sponsor. No subjects in Cohort E will receive placebo. • E1) 900 mg SC every 4 weeks for 12 weeks; all subjects will be given the option to extend treatment to 24 weeks • E2) Optional Dose considered safe in Cohort B +/- C, given subcutaneously at 8 or 12 weeks for 24 weeks • E3) Optional Dose considered safe in Cohort B +/- C, given subcutaneously 8 or 12 weeks for 24 weeks 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. Cohort G: (Phase 2a) will explore multiple doses of open-label BJT-778 for 24 weeks along with low-dose nivolumab given at Week 4 and Week 24 of treatment. Approximately 10 subjects planned. Subjects completing Cohort B who also meet the additional entry criteria for Cohort G will be eligible for enrollment. Cohort G may enroll in parallel to E and F and will be given BJT-778 900 mg SC q 4 weeks for 24 weeks along with low-dose nivolumab (0.3 mg/kg) given IV at Weeks 4 and 24.
Sponsors
Bluejay Therapeutics Inc.
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
• Male or female adults between 18 and 70 years of age • BMI 18 to 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 E and F: greater than or equal to 10 IU/mL - Cohort G more than equal to 10 and less than equal to 3000 IU/mL
Exclusion criteria
• Evidence of cirrhosis • History of decompensated liver disease • History of liver disease other than Hepatitis B • 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. - positive Serum HDV Ab -Cohort G only- •History of autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis, thyroiditis) • Presence of anti-thyroid antibodies (anti-TSHR, anti-TG, or anti-TPO) at Screening • Abnormal TSH at Screening • ANA >1:160 at Screening
Outcome results
None listed