Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000105640
Ethics application status
Approved
Date submitted
13/01/2023
Date registered
30/01/2023
Date last updated
31/08/2023
Date data sharing statement initially provided
30/01/2023
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) and Chronic HDV Infection (CHD).
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 3 conducted in individuals with chronic hepatitis B and D co-infection.
Secondary ID [1] 308355 0
BJT-778-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B Virus (HBV) Infection 328146 0
Chronic Hepatitis D Virus (HDV) Infection 328147 0
Condition category
Condition code
Infection 325198 325198 0 0
Other infectious diseases
Oral and Gastrointestinal 325557 325557 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) and Chronic Hepatitis D Virus Infection (CHD). Cohort D: Dosing of Groups D1 (Dose 1) may initiate when the Dose 1 is deemed safe in healthy volunteers (Group A1) by the Safety Review Committee (SRC) at the Day 14 safety review. Dose escalation to Dose 2 (Group D2) 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 participants from B1, and enrolled participants from D1) 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 and D3) 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, and D2) per SRC review.
Subjects will be monitored with serial vitals, ECGs, safety laboratory assessments, and AEs recording.
Cohort D all will receive open-label BJT-778 and target 4 subjects per dose.
Cohort D: CHB+CHD coinfection:
• D1) Dose 1 ×1 subcutaneously (SC)
• D2) Dose 2 ×1 SC
• D3) Optional Dose 3 ×1 SC
Cohort F: Once the safety and antiviral activity in Cohort D are established for a given dose (i.e., Dose 1), optional open-label multidose BJT-778 cohorts may be initiated and at different dosing intervals (i.e., every1, 2 or 4 weeks). The decision to initiate multidose cohorts for a given dose (i.e., Dose 1) will be determined by safety and maximum HDV RNA reductions observed with a single dose.
Approximately 8 subjects per dosing cohort will be enrolled in Cohort F. For a given dose (i.e., Dose 1), cohorts exploring different intervals may enroll simultaneously or sequentially at the discretion of the Sponsor.
• F1) Optional Dose considered safe in Cohort D, given subcutaneously at a TBD interval for 12 weeks
• F2) Optional Dose considered safe in Cohort D, given subcutaneously at a TBD interval for 12 weeks
All Subjects will continue their nucleos(t)ide treatment for the duration of the study
including the follow up.
Doses fall within the range of 75mg to 900mg and the exact doses will be disclosed after IP restrictions are met.
Intervention code [1] 324802 0
Treatment: Drugs
Comparator / control treatment
No control groups.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333032 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] 333032 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 for Cohort D and from Screening to Day 169 for Cohort F. Some of the known/possible adverse events are Immune-complex disease, changes in liverfunction/liver related blood tests and risk of allergic reactions.
Safety labs are collected regularly throughout the study from screening up to 12 weeks for Cohort D and from screening up to 24 weeks for Cohort F, 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 for Cohort D and at screening and Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141 and Day 169 post-dose for Cohort F.
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 are collected at screening, Days 1, 8, 15, 29, 57 and Day 85 post dose for Cohort D and at screening, Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141 and Day 169 post-dose for Cohort F.
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 for Cohort D and from Screening to Day 169 post-dose for Cohort F.
Supine ECGs will be performed before blood draws in Screening.
Secondary outcome [1] 415580 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] 415580 0
PK blood samples are collected as follows:
Cohort D: 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)
Cohort F: Day 1 (pre-dose), Days 8, 15, 29, 43, 57, 71, 85, 113, 141, 169 post-dose.
Secondary outcome [2] 415998 0
To evaluate the immunogenicity of BJT-778 by assessing levels of anti-drug antibodies (ADAs)
Timepoint [2] 415998 0
Blood samples are collected at regular intervals - once on Day 1, 15, 29, 57, 85 post-dose for Cohort D and once on Day 1, 29, 57, 85, 169 post-dose for Cohort F and stored for analysis of ADAs.
Secondary outcome [3] 416914 0
To evaluate the anti-HDV activity of BJT-778 by assessing HDV RNA levels
Timepoint [3] 416914 0
Participants will be assessed for changes in absolute HDV RNA levels. Blood samples will be collected regularly throughout treatment and follow up i.e.,
For Cohort D: Day 1, 2, 4, 8, 15, 29, 57, 85 post-dose
For Cohort F: Day 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169 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 D and F: greater than or equal to 10 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.
• Must have quantifiable serum HDV RNA levels at screening
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 as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices
• History of liver disease other than Hepatitis B (i.e., NASH, alcohol associated hepatitis, cholestatic liver disease, etc.)
• Chronic hepatitis C virus (HCV) infection; subjects with past HCV RNA infection that was successfully treated must be HCV RNA negative and at least 24 weeks post treatment.
• 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
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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2023
Actual
20/05/2023
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
18/07/2024
Actual
Sample size
Target
32
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 23510 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 23511 0
The Alfred - Melbourne
Recruitment hospital [3] 23662 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 38918 0
2050 - Camperdown
Recruitment postcode(s) [2] 38919 0
3004 - Melbourne
Recruitment postcode(s) [3] 39085 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 25744 0
Moldova, Republic Of
State/province [1] 25744 0
Chisinau
Country [2] 25745 0
Ukraine
State/province [2] 25745 0
Zhytomyr
Country [3] 25746 0
New Zealand
State/province [3] 25746 0
Auckland
Country [4] 25747 0
Hong Kong
State/province [4] 25747 0
Sha Tin
Country [5] 25748 0
Hong Kong
State/province [5] 25748 0
Pok Fu Lam

Funding & Sponsors
Funding source category [1] 312596 0
Commercial sector/Industry
Name [1] 312596 0
Bluejay Therapeutics Inc
Country [1] 312596 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] 314210 0
None
Name [1] 314210 0
Address [1] 314210 0
Country [1] 314210 0
Other collaborator category [1] 282477 0
Commercial sector/Industry
Name [1] 282477 0
Novotech (Australia) Pty Limited
Address [1] 282477 0
Novotech (Australia) Pty Limited
Level 3, 235 Pyrmont Street Sydney, NSW, Australia - 2009
Country [1] 282477 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311923 0
Central Health and Disability Ethics Committees (HDEC)
Ethics committee address [1] 311923 0
Health and Disability Ethics committee, Ministry of Health, 133 Molesworth Street PO Box 5013, Wellington 6011
Ethics committee country [1] 311923 0
New Zealand
Date submitted for ethics approval [1] 311923 0
01/11/2022
Approval date [1] 311923 0
15/11/2022
Ethics approval number [1] 311923 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 participants with Chronic HBV Infection (CHB) and Chronic HDV Infection (CHD).
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 122850 0
Prof Ed Gane
Address 122850 0
New Zealand Clinical Research 3 Ferncroft St, Grafton Auckland 1010 New Zealand
Country 122850 0
New Zealand
Phone 122850 0
+64 021548371
Fax 122850 0
Email 122850 0
EdGane@adhb.govt.nz
Contact person for public queries
Name 122851 0
Ms Carole Ann Moore
Address 122851 0
Vice President, Clinical Operations, 400 Concar Drive, Suite 3-101, San Mateo, CA 94404
Country 122851 0
United States of America
Phone 122851 0
+001 650 796 5003
Fax 122851 0
Email 122851 0
cmoore@bluejaytx.com
Contact person for scientific queries
Name 122852 0
Dr Nancy Shulman, MD
Address 122852 0
Nancy Shulman, MD
Chief Medical Officer
951 Mariners Island Blvd., Suite 300
San Mateo, CA 94404
Country 122852 0
United States of America
Phone 122852 0
+0016506650669
Fax 122852 0
Email 122852 0
nshulman@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.