Not Yet RecruitingPhase 1ACTRN12625000142437

A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Cavrotolimod in Subjects with Chronic Hepatitis B Infection

A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Cavrotolimod Alone and in Combinations in Participants with Chronic Hepatitis B Infection- Part C

Sponsor

Bluejay Therapeutics, Inc

Enrollment

60 participants

Start Date

Jun 16, 2025

Study Type

Interventional

Conditions

Chronic Hepatitis B Infection

Summary

This is a Phase 1b study to evaluate the safety and tolerability, PK/PD, and antiviral activity/efficacy of cavrotolimod and cavrotolimod-containing combinations in CHB infected subjects who are on nucleos(t)ide therapy. Cavrotolimod ±Nivolumab is being developed to address the high unmet medical need with possible benefits for participants with Chronic Hepatis B virus infection (CHB). This study will enroll non-cirrhotic, chronic hepatitis B (CHB) infected adults aged 18-65 years of age, inclusive, on nucleos(t)ide therapy. The study consists of four parts (Part A, Part B, Part C and Part D). Part C is an open label study with 3 cohorts. Each cohort will enroll a total of approximately 20 participants.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria26

Male or female adults between 18 and 65 years of age, inclusive
Chronic HBV infection greater than or equal to 6 months (e.g., positive for serum HBsAg greater than or equal to 6 months)
Taking a commercially available nucleos(t)ide analogs for at least 2 months prior to Screening, and willing to remain on stable treatment for the duration of the study, unless they achieve nucleos(t)ide stopping criteria.
HBV DNA less than 100 IU/mL in blood at Screening
HBsAg at Screening:
a. Part C: Cohort 1: >LLOQ to 3000 IU/mL. Optional cohorts and expansion participants/cohorts (including Cohort 1), the upper limit of 3000 IU/mL may be removed based on emerging data.
a. Presence of anti-thyroid antibodies (anti-thyroid-stimulating hormone receptor, anti-thyroglobulin [TG], or anti- thyroid peroxidase [TPO])
b. Abnormal thyroid stimulating hormone
c. Anti-nuclear antibody greater than 1:160
d. ALT or aspartate aminotransferase (AST) greater than 2× upper limit of normal (ULN)
e. Total bilirubin greater than 1.2× ULN, except for participants with Gilbert’s (normal direct bilirubin)
f. Serum albumin less than .5 g/dL
g. International normalized ratio (INR) greater than 1.2
h. Platelet count less than 140 K/mm3
i. Hemoglobin less than 12.0 g/dL for males and <11.0 g/dL for females
j. Absolute neutrophil count less than 1000/mm3
k. Estimated glomerular filtration rate less than 50 mL/min/1.73 m2 by Cockcroft-Gualt
12-lead electrocardiogram (ECG) showing the following: having a corrected QTc interval greater than 450 msec for males and greater than 470 msec for females or <340 msec (Fridericia’s correction)
Clinically significant medical history of:
a. Cardiac diseases (e.g., myocardial infarctions, stroke, arrhythmia, heart failure, and coronary heart disease)
b. Autoimmune diseases (e.g., lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis, thyroiditis), or
c. Malignancies within 3 years. Malignancy that has been successfully surgically resection and considered cured would not exclude the participant
Treatment with an investigational drug, biological agent or device within 4 weeks or 5 half-lives prior to Screening, whichever is longer.
History of excess alcohol consumption within 1 year of Screening, defined as weekly intake of greater than or equal to 14 drinks per week (average of greater than or equal to 2 drinks per day)
History of drug abuse/addiction within 6 months of Screening (except cannabis)
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 individual participating in or completing the study

Exclusion Criteria11

Pregnant or nursing females
Male or female participants of childbearing potential unwilling to comply with contraception requirements during the study
Fibroscan greater than or equal to 8.5 kPa within 1 year of Screening
History of and/or current decompensated liver disease as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal variceal bleeding
Presence of liver disease, not including chronic HBV infection, such as nonalcoholic steatohepatitis (NASH), alcohol-associated hepatitis, cholestatic liver disease, other viral (e.g., HCV or HDV) 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 greater than or equal to 6 months prior to Screening.
Positive for HIV, HDV, or HCV infection at Screening
Received solid organ or bone marrow transplant
Chronic systemic immunosuppressive therapy (e.g., prednisone) within 1 month of Screening or require the use of during the study.
Prior or current history of hepatocellular carcinoma (HCC) or suspected HCC as evidenced by screening alpha-fetoprotein greater than or equal to 20 ng/mL
History of hypersensitivity to any of the components in the cavrotolimod, BJT-778 or nivolumab formulation components or severe reactions to injections

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Interventions

Investigational Product (IP): Cavrotolimod and Nivolumab Dosage Form: Vial Method of administration: Sub cutaneous injection Dose: Cavrotolimod will be supplied as 2mL vial and Nivolumab will be s

Investigational Product (IP): Cavrotolimod and Nivolumab Dosage Form: Vial Method of administration: Sub cutaneous injection Dose: Cavrotolimod will be supplied as 2mL vial and Nivolumab will be supplied as 4mL vial This study consists of 4 parts (Part A, B, C and D). This registration is for Part C. Part C will evaluate open-label cavrotolimod plus low-dose nivolumab, a mAb targeting PD-1, in combination. Low dose of Nivolumab (0.3 mg/kg) given IV will also be administered only on day 1 for Part C. The study design has 3 cohorts with approximately 20 participants per cohort. Part C may begin once one or more cavrotolimod dose has been deemed safe in Part A (ACTRN12624000808549) by the SRC. - Cohort 1, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) for 4 weeks + low dose nivolumab (0.3 mg/kg) given IV on Day 1 - Optional Cohort 2, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) for 4 weeks + low dose nivolumab (0.3 mg/kg) given IV on Day 1 - Optional Cohort 3, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) for 4 weeks + low-dose nivolumab (0.3 mg/kg) given IV on Day 1 Participants will be followed for 12 weeks after the last dose of study medications. Participants who achieve HBsAg loss (HBsAg <LLOQ) at the end of follow up will continue to be followed for an additional 12 weeks (total 24 weeks of follow up). The difference between these cohorts will be determined by the SRC at the time of opening. Cohorts 2 and 3 are optional cohorts and may open upon SRC decision.