RecruitingPhase 1ACTRN12624000808549

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 Subjects with Chronic Hepatitis B Infection- Part A

Sponsor

Bluejay Therapeutics, Inc

Enrollment

40 participants

Start Date

Aug 5, 2024

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 ± BJT-778 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 two parts (Part A and Part B). Part A is multiple ascending dose study with 5 cohorts. Each cohort will enroll a total of 4 participants with 3 randomized to treatment arm and 1 randomized to the placebo treatment arm. Safety Review Committee will review the participant safety data as needed and determine dose escalation to the next cohort.

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 A: greater than LLOQ
a. Presence of anti-thyroid antibodies (anti-thyroid-stimulating hormone receptor [TSHR], anti-thyroglobulin [TG], or anti- thyroid peroxidase [TPO])
b. Abnormal thyroid stimulating hormone (TSH)
c. ANA 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 subjects 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 lass 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 subject.
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 subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study

Exclusion Criteria11

Pregnant or nursing females
Male or female subjects 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 formulation or severe reactions to injections

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Interventions

Investigational Product (IP): Cavrotolimod and BJT-778 Dosage Form: Vial Method of administration: Sub cutaneous injection Dose: Cavrotolimod will be supplied as 2mL vial and BJT-778 will be supp

Investigational Product (IP): Cavrotolimod and BJT-778 Dosage Form: Vial Method of administration: Sub cutaneous injection Dose: Cavrotolimod will be supplied as 2mL vial and BJT-778 will be supplied as 6 mL glass vial. The study consists of Two parts (Part A and Part B). This registration contains details of Part A. Part A is a randomized, double-blind, placebo-controlled portion of the study to evaluate multiple ascending doses (MAD) of cavrotolimod (20 mg/mL vial) administered subcutaneously (SC) in sequential cohorts. Four (4) subjects per cohort will be enrolled and randomized 3:1, active to placebo, respectively Part A- Cohort 1: Cavrotolimod 2 mg or placebo administered SC every week for 1 month Cohort 2: Cavrotolimod (less than equal to) 6 mg or placebo administered SC for 1 month Cohort 3: Cavrotolimod (less than equal to) 16 mg or placebo administered SC for 1 month Optional Cohort 4: Cavrotolimod (less than equal to) 24 mg or placebo administered SC for 1 month Optional Cohort 5: Cavrotolimod (less than equal to) 24 mg or placebo administered SC for 1 month. Subjects will continue to be followed for 5 weeks after the last dose of cavrotolimod. Dose escalation to next cohort will only proceed only safety review meetings where it is confirmed to proceed to next dosing cohort, Emerging safety and PD data will be reviewed at Safety Review Meetings to confirm the dose and frequency of SC administration (e.g., weekly or extend to every 2 weeks) of cavrotolimod to be evaluated in Cohorts 2-5. Adherence is not monitored as cavrotolimod or placebo will be injected by the site staff. Optional cohorts 4 and 5 may be included to explore additional dose levels and/or dosing regimens. Optional cohorts 4 and 5 may also be included to extend an existing dose level and/or dosing regimens for the purposes of gathering further information at that dose level.