Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000809538
Ethics application status
Approved
Date submitted
31/05/2024
Date registered
1/07/2024
Date last updated
19/09/2024
Date data sharing statement initially provided
1/07/2024
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 Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Cavrotolimod Alone and in Combinations in Subjects with Chronic Hepatitis B Infection
Secondary ID [1] 312229 0
BJT-008-001
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12624000808549

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Infection 333930 0
Condition category
Condition code
Infection 330601 330601 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product (IP): Cavrotolimod and BJT-778
Dosage Form: Vial
Method of administration: Sub cutaneous (SC) 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 details are for Part B. Part B will evaluate open-label, cavrotolimod plus BJT-778, a HBsAg (Hepatitis B surface antigen) monoclonal antibody, in combination. Part B may initiate once a cavrotolimod dose has been deemed safe in Part A and will enroll upto 80 subjects. Study consists of 3 cohorts and each cohort/arm will enroll 10-15 subjects.

- Cohort 1- Arm 1 and Expansion Arm 1a, Cavrotolimod (less than equal to 24 mg) for 4 weeks plus BJT-778 (less than equal to 900mg) SC every 4 weeks for 6 months.
Arm 2 and Expanded Arm 2a, 4-week lead-in of BJT-778 (less than equal to 900mg) SC every 4 weeks then cavrotolimod (less than equal to 24 mg) for 4 weeks plus BJT778 for 5 months.
- Optional Cohort 2- Arm 1 and Expansion 1a, Cavrotolimod (less than equal to 24 mg) for 4 weeks plus BJT-778 (less than equal to 900mg) SC every 4 weeks for 6 months
- Optional Cohort 3- Arm 1 and Expansion 1a, 4-week lead-in of BJT-778 (less than equal to 900mg) SC every 4 weeks then cavrotolimod (less than equal to 24 mg) for 4 weeks plus BJT-778 for 5 months.

Subjects will be followed for 12 weeks after the last dose of study medications. Subjects who achieve HBsAg loss {HBsAg <LLOQ (lower limit of quantification)} at the end of follow up will continue to be followed for an additional 12 weeks (total 24 weeks of follow up).

Optional cohorts 2 and 3 may be included to explore additional dose levels and/or dosing regimens. Optional cohorts 2 and 3 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. The number of subjects in a dose cohort in either Part A or B can be extended to gather further information on a dosing regimen. Expansion arm enrollment may overlap with original arm conduct; however, expansion arms will only be opened once original arm has completed enrollment. The maximum expansion is 100% of the original cohort size at the select dose level, however, all will receive open label cavrotolimod. Adherence is not monitored as cavrotolimod will be injected by the site staff.
Intervention code [1] 328680 0
Treatment: Drugs
Comparator / control treatment
comparator - Arm 1
Control group
Active

Outcomes
Primary outcome [1] 338350 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

All measures will be assessed as composite outcome.
Timepoint [1] 338350 0
-Adverse events monitored daily from screening to end of study (EOS) 48 weeks post first dose administration.
- Safety Lab parameters will be monitored on screening, Day 1, Day 85 and Day 169, 36 weeks and 48 weeks post first dose administration.
- Vital signs will be assessed on site visits from screening to EOS 48 weeks post first dose administration.
Secondary outcome [1] 435573 0
To evaluate the plasma pharmacokinetics (PK) of cavrotolimod alone, in combinations, and/or other investigational agents) (e.g., BJT778)
Timepoint [1] 435573 0
Blood samples will be collected on screening. Day 1 (Predose (within 4 hours prior to dose), 2-hour (±10 min), 4 hours (±15 min), and 8 hours (±15 min) post dose), Day 29, Day 57, Day 85, Day 113, day 141, Day 169, 28 weeks, 32weeks, 36 weeks and 48 weeks post first dose administration.
Secondary outcome [2] 435574 0
To evaluate the pharmacodynamics (PD) of cavrotolimod alone and in combinations
Timepoint [2] 435574 0
Blood samples will be collected on Day 1, Day 29. Day 57, Day 85, Day 113, Day 141, Day 169, 28 weeks, 32 weeks, 36 weeks and 48 weeks post first dose administration.
Secondary outcome [3] 435575 0
To evaluate the anti-hepatitis B virus (HBV) activity of cavrotolimod alone and in combinations.
Timepoint [3] 435575 0
Blood samples will be collected on Day 1, Day 29, Dat 57, Day 169, 28 weeks, 36 weeks and 48 weeks post first dose administration.
Secondary outcome [4] 435576 0
To evaluate efficacy of cavrotolimod combination treatment
Timepoint [4] 435576 0
Blood samples will be collected on Day 1, Day 29. Day 57, Day 85, Day 113, Day 141, Day 169, 28 weeks, 32 weeks, 36 weeks and 48 weeks post first 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 B Cohort 1: greater than LLOO to 3000 IU/mL.
In Part B, optional Cohorts and expansion subjects/arm/cohort (including Cohort 1), 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 subjects 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 formulation 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 subject unsuitable for inclusion:
a. Presence of anti-thyroid antibodies (anti-thyroid-stimulating hormone receptor ITSHRI, anti­ thyroglobulin ITGI, or anti- thyroid peroxidase [TPO])
b. Abnormal thyroid stimulating hormone (TSH)
c. ANA greater than 1160
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 fltration rate lass 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 subject.
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 subject unsuitable for inclusion, or could interfere with the subject 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 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/01/2025
Actual
Date of last participant enrolment
Anticipated
30/06/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment outside Australia
Country [1] 26338 0
New Zealand
State/province [1] 26338 0
Auckland
Country [2] 26339 0
Hong Kong
State/province [2] 26339 0
Country [3] 26342 0
Moldova, Republic Of
State/province [3] 26342 0
Country [4] 26343 0
Taiwan, Province Of China
State/province [4] 26343 0
Country [5] 26344 0
Philippines
State/province [5] 26344 0
Country [6] 26345 0
Ukraine
State/province [6] 26345 0

Funding & Sponsors
Funding source category [1] 316607 0
Commercial sector/Industry
Name [1] 316607 0
Bluejay Therapeutics, Inc
Country [1] 316607 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] 318791 0
None
Name [1] 318791 0
Address [1] 318791 0
Country [1] 318791 0
Other collaborator category [1] 283057 0
Commercial sector/Industry
Name [1] 283057 0
Novotech (Australia) Pty Ltd
Address [1] 283057 0
Country [1] 283057 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315391 0
Bellberry Human Research Ethics Committee F
Ethics committee address [1] 315391 0
Ethics committee country [1] 315391 0
Australia
Date submitted for ethics approval [1] 315391 0
29/05/2024
Approval date [1] 315391 0
Ethics approval number [1] 315391 0
Ethics committee name [2] 315392 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [2] 315392 0
Ethics committee country [2] 315392 0
Australia
Date submitted for ethics approval [2] 315392 0
17/05/2024
Approval date [2] 315392 0
15/07/2024
Ethics approval number [2] 315392 0
108290
Ethics committee name [3] 315393 0
Northern A Health and Disability Ethics Committee 
Ethics committee address [3] 315393 0
Ethics committee country [3] 315393 0
New Zealand
Date submitted for ethics approval [3] 315393 0
27/05/2024
Approval date [3] 315393 0
Ethics approval number [3] 315393 0

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

Contacts
Principal investigator
Name 134558 0
Prof Edward Gane
Address 134558 0
New Zealand Clinical Research, Grd floor, 3 Ferncroft St, Grafton Auckland 1010 New Zealand
Country 134558 0
New Zealand
Phone 134558 0
+64 21 548 371
Fax 134558 0
Email 134558 0
[email protected]
Contact person for public queries
Name 134559 0
Ms. Carole Ann Moore
Address 134559 0
Bluejay Therapeutics, Inc., Vice President, Clinical Operations, 400, Concar Drive, Suite 3-101 San Mateo, CA
Country 134559 0
United States of America
Phone 134559 0
+1 650 796 5003
Fax 134559 0
Email 134559 0
[email protected]
Contact person for scientific queries
Name 134560 0
Jenny Stanton, PharmD, VP, Head of ID Clinical Development
Address 134560 0
Bluejay Therapeutics, Inc., 400 Concar Drive Suite 3-101 San Mateo, CA 94402
Country 134560 0
United States of America
Phone 134560 0
+1 650 504 5212
Fax 134560 0
Email 134560 0
[email protected]

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.