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Trial registered on ANZCTR


Registration number
ACTRN12623000078651
Ethics application status
Approved
Date submitted
1/12/2022
Date registered
24/01/2023
Date last updated
31/08/2023
Date data sharing statement initially provided
24/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of BJT-778 in Subjects with Chronic HBV Infection (CHB).
Scientific title
A Phase 1/2a, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of BJT-778 in Healthy Volunteers and in Subjects with Chronic Hepatitis B Infection, Including Subjects with Chronic Hepatitis D Infection - Part 2 conducted in Subjects with Chronic Hepatitis B Infection
Secondary ID [1] 308354 0
BJT-778-001
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study follows up from ACTRN12623000075684.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Virus (HBV) Infection 328145 0
Condition category
Condition code
Infection 325197 325197 0 0
Other infectious diseases
Oral and Gastrointestinal 325517 325517 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BJT-778 is being developed as a potent, selective neutralizing monoclonal antibody for the treatment of Chronic Hepatitis B Virus Infection (CHB). Dosing of Groups B1 (Dose 1) may initiate when the Dose 1 is deemed safe in healthy volunteers (Group A1) by the SRC at the Day 14 safety review. Dose escalation to Dose 2 (Groups B2, C2) may proceed when the Day 14 safety review of the healthy volunteers at the Dose 2 (Group A2) and the Dose 1 in HBV-infected subjects (all subjects from B1) have determined to have acceptable safety profiles. The SRC will also incorporate available longer-term safety, efficacy, and PK data from all current and prior dosing groups into the decision making.
Dose escalation to the Optional Dose 3 in each group (B3, C3) may proceed once at least 14-day safety is established in the healthy volunteers at Dose 3 (Group A3) and 14-day safety is established at Dose 3 of the respective cohorts (B2, C2) per SRC review.
Subjects will be monitored with serial vitals, ECGs, safety laboratory assessments, and AEs recording.
Doses of BJT-778 in Cohort B and C include:
Cohort B – Subjects with CHB with lower HBsAg levels:
• B1) Dose 1 x 1 subcutaneously (SC)
• B2) Dose 2 x 1 SC
• B3) Optional Dose 3 x 1 SC
Cohort C – Subjects with CHB with higher HBsAg levels:
• C2) Dose 2 x 1 SC
• C3) Optional Dose 3 x 1 SC
Doses fall within the range of 75mg to 900mg and the exact doses will be disclosed after IP restrictions are met.
Intervention code [1] 324801 0
Treatment: Drugs
Comparator / control treatment
Placebo controlled trial
Participants randomized to placebo will receive sterile 0.9% normal saline at the same volume as the BJT-778 dose in that dosing cohort.
Doses of placebo in Cohort B and C include:
Cohort B – Subjects with CHB with lower hepatitis B surface antigen (HBsAg) levels:
• B1) Dose 1 placebo x 1 Subcutaneously (SC)
• B2) Dose 2 placebo x 1 SC
• B3) Optional Dose 3 placebo x 1 SC
Cohort C – Subjects with CHB with higher HBsAg levels:
• C2) Dose 2 placebo x 1 SC
• C3) Optional Dose 3 placebo x 1 SC
Placebo will be drawn up into a syringe(s) for injection and labeled with the subject identification number by an unblinded pharmacist.
Control group
Placebo

Outcomes
Primary outcome [1] 333031 0
To evaluate the safety and tolerability of BJT-778. Subjects will be monitored with serial vitals, ECGs, safety labs, and adverse events recording from Screening to End of Treatment.
Timepoint [1] 333031 0
Participants will be assessed daily for adverse events from baseline to end of treatment visit. Adverse events are recorded using Division of AIDS Adverse Experience Reporting System (DAERS) from Screening to Day 85. Some of the known/possible adverse events are Immune-complex disease, changes in liver function/liver related blood tests and risk of allergic reactions.
Safety labs are collected regularly throughout the study from screening up to 12 weeks, these include Blood chemistries, Hematology, Complement studies (C3, C5a, Bb) and Urinalysis.
Blood samples for Blood chemistries, Hematology are collected at screening and Days 1, 2, 8, 15, 29, 57 and Day 85 post-dose.
Blood samples for complement studies (C3, C5a, Bb) are collected post-dose on Day 1, 15, 29 and 85, as well as at any time post-dose if immune-complex disease is suspected.
Urine samples will be collected regularly throughout the study from Screening to Day 85 post dose.
Vital signs will be collected at every visit – heart rate measured using a pulse oximeter, blood pressure measured using a sphygmomanometer, temperature measured using a thermometer and respiratory rate counted by qualified personnel - all will be performed before blood draws from Screening to Day 85 post dose.
Supine ECGs will be performed before blood draws in Screening.
Secondary outcome [1] 415579 0
To evaluate the plasma pharmacokinetics of BJT-778. PK parameters include but are not limited to Cmax, Clast, Tmax, Tlast, AUCinf, AUClast, t1/2, Lambda z, WF, and CL/F
Timepoint [1] 415579 0
PK blood samples are collected as follows:
• Cohorts B and C: Day 1 (pre-dose, 1, 4, and 8 hrs post-dose) and at every visit after dosing (Days 2, 4, 8, 15, 29, 57, and 85 post-dose).
Secondary outcome [2] 415993 0
To evaluate the immunogenicity of BJT-778 by assessing levels of anti-drug antibodies (ADAs)
Timepoint [2] 415993 0
Blood samples are collected at regular intervals (for Cohorts B and C once on Day 1, 15, 29, 57, 85 post-dose) and stored for analysis of ADAs.
Secondary outcome [3] 415994 0
To evaluate the anti-viral efficacy of BJT-778 by assessing HBsAg levels
Timepoint [3] 415994 0
Participants will be assessed for changes in absolute HbsAg levels or Anti-HBsAg activity. 2 blood samples for quantitative HBsAg measurements are collected regularly throughout treatment and follow up i.e., twice on Day 1, 2, 4, 8, 15, 29, 57, 85 post-dose.

Eligibility
Key inclusion criteria
• Able and willing to provide written informed consent (signed and dated) and any authorizations required by local law and can comply with all study requirements
• Male or female adults between 18 and 70 years of age
• BMI 18-40 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 B: lower HBsAg levels (less than 3000 IU/mL)
- Cohort C: higher HBsAg levels (greater than 3000 IU/mL)
• Females: Non-pregnant and non-lactating; surgically sterile, post-menopausal or, if engaged in sexual relations of childbearing potential, subject is using an acceptable contraceptive method from the time of signing the informed consent form until at least 12 weeks after the last dose of Study Drug.
• Males: Surgically sterile or if engaged in sexual relations with a female of child-bearing potential, subject is utilizing an acceptable contraceptive method during treatment with Study Drug and for at least 12 weeks after the last dose of Study Drug. Agree not to donate sperm for at least 12 weeks after the last dose of Study Drug.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2023
Actual
2/05/2023
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
30/04/2024
Actual
Sample size
Target
40
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 23507 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 23508 0
The Alfred - Melbourne
Recruitment hospital [3] 23663 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 38915 0
2050 - Camperdown
Recruitment postcode(s) [2] 38916 0
3004 - Melbourne
Recruitment postcode(s) [3] 39086 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 25739 0
Hong Kong
State/province [1] 25739 0
Pok Fu Lam
Country [2] 25740 0
Hong Kong
State/province [2] 25740 0
Sha Tin
Country [3] 25741 0
New Zealand
State/province [3] 25741 0
Auckland
Country [4] 25742 0
Ukraine
State/province [4] 25742 0
Zhytomyr
Country [5] 25743 0
Moldova, Republic Of
State/province [5] 25743 0
Chisinau

Funding & Sponsors
Funding source category [1] 312595 0
Commercial sector/Industry
Name [1] 312595 0
Bluejay Therapeutics Inc
Country [1] 312595 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Bluejay Therapeutics Inc.
Address
400 Concar Drive, Suite 3-101, San Mateo, CA 94402
Country
United States of America
Secondary sponsor category [1] 314209 0
None
Name [1] 314209 0
Address [1] 314209 0
Country [1] 314209 0
Other collaborator category [1] 282476 0
Commercial sector/Industry
Name [1] 282476 0
Commercial sector/Industry
Address [1] 282476 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW, Australia - 2009
Country [1] 282476 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311922 0
Central Health and Disability Ethics Committees (HDEC)
Ethics committee address [1] 311922 0
Health and Disability Ethics committee, Ministry of Health, 133 Molesworth Street PO Box 5013, Wellington 6011
Ethics committee country [1] 311922 0
New Zealand
Date submitted for ethics approval [1] 311922 0
01/11/2022
Approval date [1] 311922 0
15/11/2022
Ethics approval number [1] 311922 0
2022 FULL 13730

Summary
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 BJT-778 in patients with CHB.
Trial website
Trial related presentations / publications
Public notes
This study is being registered in four parts, which will involve the following participant cohorts:
- Part 1: conducted in healthy volunteers (Cohort A)
- Part 2: conducted in individuals with chronic hepatitis B infection, with participants sub-categorized into those with lower HbsAg levels (Cohort B) and higher HBsAg levels (Cohort C)
- Part 3: conducted in individuals with chronic hepatitis B and D co-infection (Cohorts D and F)
- Part 4: conducted in individuals with chronic hepatitis B (Cohort E)

Contacts
Principal investigator
Name 122846 0
Prof Ed Gane
Address 122846 0
New Zealand Clinical Research 3 Ferncroft St, Grafton Auckland 1010 New Zealand
Country 122846 0
New Zealand
Phone 122846 0
+64 021548371
Fax 122846 0
Email 122846 0
[email protected]
Contact person for public queries
Name 122847 0
Ms Carole Ann Moore
Address 122847 0
Vice President, Clinical Operations, 400 Concar Drive, Suite 3-101, San Mateo, CA 94404
Country 122847 0
Australia
Phone 122847 0
+001 650 796 5003
Fax 122847 0
Email 122847 0
[email protected]
Contact person for scientific queries
Name 122848 0
Dr Nancy Shulman, MD
Address 122848 0
Nancy Shulman, MD
Chief Medical Officer
951 Mariners Island Blvd., Suite 300
San Mateo, CA 94404
Country 122848 0
United States of America
Phone 122848 0
+0016506650669
Fax 122848 0
Email 122848 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.