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Trial registered on ANZCTR


Registration number
ACTRN12625000173493p
Ethics application status
Submitted, not yet approved
Date submitted
4/12/2024
Date registered
14/02/2025
Date last updated
14/02/2025
Date data sharing statement initially provided
14/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Cavrotolimod in Subjects with Chronic Hepatitis B Infection
Scientific title
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 D
Secondary ID [1] 313328 0
BJT-008-001
Universal Trial Number (UTN)
Trial acronym
Linked study record
This registration is linked to ACTRN12624000809538 (Part B of the study) and ACTRN12624000808549 (Part A of the study). The study has been expanded to include Part C (ACTRN12625000142437) and Part D (this registration) via a protocol amendment.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Infection 335687 0
Condition category
Condition code
Infection 332248 332248 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product (IP): Cavrotolimod, Nivolumab and BJT-778
Dosage Form: Vial
Method of administration: Sub cutaneous injection (SC)
Dose: Cavrotolimod will be supplied as 2mL vial; Nivolumab will be supplied as 4mL vial and BJT-778 will be supplied as 6 mL glass vial.

This study consists of 4 parts (Part A, B, C and D). This registration is for Part D. Part D will evaluate up to 48-week combination regimen(s) with cavrotolimod ± BJT-778 ± lowdose nivolumab for the treatment of Chronic Hepatitis B infection (CHB). The open-label combination regimens(s) to be tested in Part D will be confirmed by the SRC based on review of emerging safety, tolerability, antiviral activity, and PK/PD, including BJT-008-001 Part B (ACTRN12624000809538) and Part C and BJT-778-001 evaluating BJT-778 900 mg administered SC every 4 weeks in combination with low-dose nivolumab 0.3 mg/kg IV at Week 4 and 24. This will include review of 8-week safety data from BJT-008-001 Part B, 4week safety data from BJT-008-001 Part C, and 24-weeks of safety data from BJT-778-001 Cohort G (New protocol in development with BJT-778 and Nivolumab).

The combination regimen(s) will not exceed a total duration of 48 weeks. 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.
• Cohort 1, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) SC ± BJT-778 900 mg SC every 4 weeks ± low-dose nivolumab (0.3 mg/kg) every 3 months for up to 48 weeks
• Optional Cohort 2, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) SC ± BJT-778 900 mg SC every 4 weeks ± low-dose nivolumab (0.3 mg/kg) every 3 months for up to 48 weeks
• Optional Cohort 3, Arm 1 and Expansion Arm 1a will receive Cavrotolimod (less than equal to 24 mg) SC ± BJT-778 900 mg SC every 4 weeks ± low-dose nivolumab (0.3 mg/kg) every 3 months for up to 48 weeks

Participants will be followed for 24 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 24 weeks (total 48 weeks of follow up). Part D may not start until after review of the 4-week safety data from Part C.
Interim safety, tolerability and available efficacy data will be reviewed by the SRC when the first =5 participants in a cohort A have completed 12 weeks of treatment and 24 weeks of treatment. The SRC can recommend modification to study medication or safety monitoring, discontinue a treatment arm, or discontinue the study. Additional cohorts may also be initiated based on the emerging data and SRC recommendation. The selected dose(s), regimen(s), and combination(s) to be evaluated in Part D will be agreed upon by the SRC.
Intervention code [1] 329911 0
Treatment: Drugs
Comparator / control treatment
None.
All assessments before the first dose of study medication will be considered as baseline. If there are multiple baseline assessments, the most recent one will be used for statistical analysis.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339822 0
To evaluate the safety and tolerability of cavrotolimod alone and in combinations. - Incidence and severity of treatment-emergent adverse events (TEAEs) will be assessed for severity and causality (relationship of event to the investigational product) by the study investigator using the specified definitions. AEs/SAEs will be coded and tabulated using the Medical Dictionary for Regulatory Activities (current version at study start). - Changes in clinical laboratory parameters including blood tests for complete blood count. coagulation, serum chemistry, and urinalysis. - Change in vital signs measurements. Vital signs include measurement of heart rate (HR) respiration rate (RR), systolic and diastolic blood pressure (BP) and body temperature. BP and HR will be measured by an automated BP Machine, RR is a manual calculation where the staff member will count the rise/fall of the chest and temperature will be measured by a digital tympanic thermometer - Changes in the electrocardiogram (ECG) findings) for exclusion criteria 12. Symptoms-driven ECGs may be collected at any time during the study for cardiac evaluation/assessment. Any symptoms-driven ECG that has clinically significant changes will be captured as an AE. All measures will be assessed as a composite outcome
Timepoint [1] 339822 0
- Adverse events monitored once every 4 weeks from screening to 24 weeks post first dose administration. - Safety Lab parameters will be assessed on screening, Day 1, Day 29, FU12, FU24, and First and Last dose of Cavrotolimod and 1st dose of Nivolumab and at 14days post dose. This will change based on the dosing frequency determinedd by the SRC. - Vital signs will be assessed once every 4 weeks from screening to 24 weeks post first dose administration. Vitals are also taken on each Cavrotolimod dose and at +24h and +48h post dose. Relative to Nivolumab dosing day vitals are taken on day 1, 7days post dose and 14days post dose. - ECG will be checked on screening.
Secondary outcome [1] 441518 0
To evaluate the plasma pharmacokinetics (PK) of cavrotolimod alone, in combinations, and/or other study medication(s) (e.g. BJT-778)
Timepoint [1] 441518 0
Blood samples will be collected at single timepoint from screening, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 196, Day 224, day 252, Day 280, Day 308, Day 336 till 48 weeks follow up weeks since last dose administration
Secondary outcome [2] 441519 0
To evaluate the pharmacodynamics (PD) of cavrotolimod alone and in combinations
Timepoint [2] 441519 0
Blood samples will be collected on screening, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 196, Day 224, day 252, Day 280, Day 308, Day 336 till 48 weeks follow up weeks since last dose administration
Secondary outcome [3] 441520 0
To evaluate the anti-hepatitis B virus (HBV) activity of cavrotolimod alone and in combinations
Timepoint [3] 441520 0
Blood samples will be collected on screening, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 196, Day 224, day 252, Day 280, Day 308, Day 336 till 48 weeks follow up weeks since last dose administration
Secondary outcome [4] 441521 0
To evaluate efficacy of cavrotolimod combination treatment
Timepoint [4] 441521 0
Blood samples will be collected on screening, Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 196, Day 224, day 252, Day 280, Day 308, Day 336 till 48 weeks follow up weeks since last dose administration.

Eligibility
Key inclusion criteria
1. Male or female adults between 18 and 65 years of age, inclusive
2. Chronic HBV infection greater than or equal to 6 months (e.g., positive for serum HBsAg greater than or equal to 6 months)
3. 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.
4. HBV DNA less than 100 IU/mL in blood at Screening
5. HBsAg at Screening:
a. Part D: >LLOQ to 3000 IU/mL. The upper limit of 3000 IU/mL may be removed based on emerging data.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or nursing females
2. Male or female participants of childbearing potential unwilling to comply with contraception requirements during the study
3. Fibroscan greater than or equal to 8.5 kPa within 1 year of Screening
4. History of and/or current decompensated liver disease as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal variceal bleeding
5. 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.
6. Positive for HIV, HDV, or HCV infection at Screening
7. Received solid organ or bone marrow transplant
8. Chronic systemic immunosuppressive therapy (e.g., prednisone) within 1 month of Screening or require the use of during the study.
9. 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
10. History of hypersensitivity to any of the components in the cavrotolimod, BJT-778 or nivolumab formulation components or severe reactions to injections
11. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion:
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. 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)
13. 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
14. Treatment with an investigational drug, biological agent or device within 4 weeks or 5 half-lives prior to Screening, whichever is longer.
15. 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)
16. History of drug abuse/addiction within 6 months of Screening (except cannabis)
17. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/10/2025
Actual
Date of last participant enrolment
Anticipated
31/03/2026
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment outside Australia
Country [1] 26695 0
New Zealand
State/province [1] 26695 0
Auckland
Country [2] 26696 0
Moldova, Republic Of
State/province [2] 26696 0
Country [3] 26697 0
Taiwan, Province Of China
State/province [3] 26697 0
Country [4] 26698 0
Hong Kong
State/province [4] 26698 0
Country [5] 26699 0
Ukraine
State/province [5] 26699 0

Funding & Sponsors
Funding source category [1] 317781 0
Commercial sector/Industry
Name [1] 317781 0
Bluejay Therapeutics, Inc
Country [1] 317781 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Bluejay Therapeutics, Inc
Address
Country
United States of America
Secondary sponsor category [1] 320099 0
None
Name [1] 320099 0
Address [1] 320099 0
Country [1] 320099 0
Other collaborator category [1] 283295 0
Commercial sector/Industry
Name [1] 283295 0
Novotech(Australia) Pty Limited
Address [1] 283295 0
Country [1] 283295 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316465 0
Bellberry Human Research Ethics Committee D
Ethics committee address [1] 316465 0
Ethics committee country [1] 316465 0
Australia
Date submitted for ethics approval [1] 316465 0
04/12/2024
Approval date [1] 316465 0
Ethics approval number [1] 316465 0
Ethics committee name [2] 316554 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [2] 316554 0
Ethics committee country [2] 316554 0
Australia
Date submitted for ethics approval [2] 316554 0
06/12/2024
Approval date [2] 316554 0
Ethics approval number [2] 316554 0
Ethics committee name [3] 316555 0
Northern A Health and Disability Ethics Committee 
Ethics committee address [3] 316555 0
Ethics committee country [3] 316555 0
New Zealand
Date submitted for ethics approval [3] 316555 0
29/11/2024
Approval date [3] 316555 0
Ethics approval number [3] 316555 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137974 0
Prof Edward Gane
Address 137974 0
New Zealand Clinical Research, Grd floor, 3 Ferncroft St, Grafton Auckland 1010 New Zealand
Country 137974 0
New Zealand
Phone 137974 0
+64 21 548 371
Fax 137974 0
Email 137974 0
edgane@adhb.govt.nz
Contact person for public queries
Name 137975 0
Ms. Carole Ann Moore
Address 137975 0
Bluejay Therapeutics Inc., 255 Shoreline Drive, Suite 450, Redwood City, CA 94065, USA
Country 137975 0
United States of America
Phone 137975 0
+1 650 796 5003
Fax 137975 0
Email 137975 0
cmoore@bluejaytx.com
Contact person for scientific queries
Name 137976 0
Susanna Tan, Senior Director, Clinical Development
Address 137976 0
Bluejay Therapeutics Inc., 255 Shoreline Drive, Suite 450, Redwood City, CA 94065, USA
Country 137976 0
United States of America
Phone 137976 0
+1 925 998 6824
Fax 137976 0
Email 137976 0
stan@bluejaytx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.