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Trial registered on ANZCTR


Registration number
ACTRN12625000204448
Ethics application status
Approved
Date submitted
3/01/2025
Date registered
21/02/2025
Date last updated
30/03/2025
Date data sharing statement initially provided
21/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Tolerability of CLB-4000 in Subjects with Chronic Hepatitis B: non-randomised cohorts
Scientific title
A Phase 1b Study Evaluating the Safety and Tolerability of CLB-4000 with or without Peg-IFNa-2a in Subjects with Chronic Hepatitis B: non-randomised cohorts
Secondary ID [1] 313613 0
CLB-4000-1-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 336158 0
Condition category
Condition code
Infection 332711 332711 0 0
Other infectious diseases
Oral and Gastrointestinal 332710 332710 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
This study has 3 cohorts and one optional cohort, Eligible participants will receive 5 monthly Intramuscular (IM) injections of CLB-4000 on Days 1, 30, 60, 90, and 120. This registration is for cohort 1, 3 and Optional cohort (non- randomised cohort)

Subjects participating in Peg-IFNa-2a arms of the study will receive a weekly subcutaneous injection of Peg-IFNa-2a 180 µg for 8 weeks during a run-in period and then for another 16 weeks during the CLB-4000 treatment phase.

1. Cohort 1 (N=5): subjects will receive CLB-4000 (250 µg CLB-405 and 250 µg CLB-505 adjuvanted with 200 µg TQL-1055)

2. Cohort 3 (N=4): subjects will receive CLB-4000 (250 µg CLB-405 and 250 µg CLB-505 adjuvanted with 400 µg TQL-1055) with 180 µg Peg-IFNa-2a

3. Optional Cohort (N=up to 8) Following review of available data by the safety review committee (SRC), in conjunction with an ongoing review of clinical activity by the Sponsor, an optional expansion of any one of, or a combination of, Cohorts 1 to 3, or a new cohort with a higher dose of TQL-1055 (up to 800 µg), may be considered . The first subject who receives CLB-4000 in each cohort or arm with a new dose level or combination will act as a sentinel subject.

The intervention (CLB-4000) is administered at the trial site and is recorded in the eCRF. Each Peg-IFNa-2a dose administration is recorded on a patient diary and includes dosing date, time, if it was self-administered or administered by a caregiver and if the full volume was administered. The diary will be review at clinic visits to check on adherence to the intervention.
Intervention code [1] 330210 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340238 0
To evaluate the safety and tolerability of CLB-4000 with and without Peg-IFNa-2a in noncirrhotic adults with CHB on a stable dose of a NUC.
Timepoint [1] 340238 0
- Adverse Event Collection will occur at Screening, Day -56, Day -28, Day -7 (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 3 (Sentinel subject only) Day 8 (sentinel subject only), Day 15, Day 30, Day 45, Day 60, Day 75 (telephone visit; sentinel subjects only), Day 90, Day 105, Day 120, Day 150 (Safety follow-up visit)and Day 300 (End of study visit) after first dose of study drug. - Vital signs will be collected at Screening, Day -56, Day -28, Day -7 (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 3 (Sentinel subject only) Day 8 (sentinel subject only), Day 15, Day 30, Day 45, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug. - Hematology and chemistry- Samples will be collected at Screening, Day -56, Day -28 and Day -7 (Peg-IFNa-2a arm only), Day 1, Day 3 (Sentinel subject only) Day 8 (sentinel subject only), Day 15, Day 30, Day 45, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug. - Thyroid panel assessments in subjects taking Peg-IFNa-2a. Blood will be collected at screening, Day -56 and Day -28, Day -7 (Peg-IFNa-2a arm only), Day 1, Day 90 and Day 150 after first dose of study drug. Thyroid panel assessment for changes for subjects taking CLB-4000 only will be assessed at screening and at Day 150. -Coagulation assessments- Blood will be collected at screening, Day -56, Day -28 and Day -7 (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 30, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug. - Urinalysis will be done at Screening, Day 1 and Day 30, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug. -ECGs will be assessed at Screening, Day -56, (Peg-IFNa-2a arm only), Day 1, Day 30, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug. - Weight will be collected at Screening, Day 1, Day 60, and Day 120 after first dose of study drug. - Complete physical examination will be done at screening, Day 1 and Day 150 (safety follow up visit) after first dose of study drug. - Targeted physical examination will be done at Day -56 (Peg-IFNa-2a arm only), Day 30, 60, 90, 120 and 300 after first dose of study drug. All outcome measures will be assessed as composite outcome.
Secondary outcome [1] 443453 0
The effect of CLB-4000 on changes in CLB-405 and/or CLB-505 specific T-cell and B cell populations. All measures will be measured as composite outcome.
Timepoint [1] 443453 0
Whole blood for PBMC (peripheral blood mononuclear cells) analysis will be collected at Day -56, (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 30, Day 45, Day 60, Day 90, Day 105, Day 120 Day 150 (Safety follow-up visit), Day 210 and Day 300 (End of study visit) after first dose of study drug.
Secondary outcome [2] 443452 0
The effect of CLB-4000 on immunological responses will be assessed by measuring serum antibodies to CLB-405 and CLB-505. All measures will be measured as composite outcome.
Timepoint [2] 443452 0
Serum samples will be collected at Day -56, (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 30, Day 45, Day 60, Day 90, Day 105, Day 120, Day 150 (Safety follow-up visit), Day 210 and Day 300 (End of study visit) after first dose of study drug
Secondary outcome [3] 443451 0
The effect of CLB-4000 on additional measures of antiviral activity will be assessed by serum HBV DNA, HBeAg, anti-HBe, HBV RNA, HBcrAg. All measures will be assessed as composite outcome.
Timepoint [3] 443451 0
Serum samples will be collected on Day -56 (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 30, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit) and Day 300 (End of study visit) after first dose of study drug.
Secondary outcome [4] 443450 0
The antiviral activity of CLB-4000 will be assessed by serum HBsAg and anti-HBs levels. The levels will be measured as composite outcome
Timepoint [4] 443450 0
Screening, and at Day -56 and Day -7 (Peg-IFNa-2a arm only), Day 1 (day of first dose), Day 15, Day 30, Day 60, Day 90, Day 120, Day 150 (Safety follow-up visit), Day 210 and Day 300 (End of study visit) after first dose of study drug.

Eligibility
Key inclusion criteria
1. Able to give written informed consent.
2. Age 18 to 60 years, inclusive
3. Body mass index (BMI) 18 to 35 kg/m2.
4. Diagnosed with CHB for at least 6 months and a HBsAg greater than 100 IU/mL and less than 500 IU/mL..
5.Anti-HBs antibodies <2.0 IU/L.
6. Serum HBV DNA <20 IU/mL for more than equal to 6 months and HBV DNA <20 IU/mL at screening
7. Has received treatment with a NUC (entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide) for at least 6 months
8. Female subjects must be surgically sterile, postmenopausal or if of childbearing potential must have a negative pregnancy test and must be willing to use highly effective forms of contraception.
9. Male subjects must be surgically sterile, abstinent, agree to use an appropriate contraception.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with any evidence of liver disease of non-HBV etiology.
2. Previous history or current diagnosis of significant liver fibrosis or cirrhosis
3. History of or suspected hepatocellular carcinoma
4. Positive testing for HIV-1, HIV-2, HCV, or HDV that suggests a concurrent infection.
5. Immunodeficient or autoimmune conditions due to disease e.g., thyroid or kidney disease or medication requiring systemic steroids within the previous 12 weeks (topical or inhaled steroids are permissible).
6. Chronic treatment with immunosuppressant within 30 days before run-in or study drug administration at the Day 1 visit and throughout the duration of study participation.
7. Cancer or treatment for cancer within 3 years before Screening. Successfully treated basal cell and squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed.
8. History of anaphylaxis, hypersensitivity, or significant drug allergies.
9. Any condition that in the investigator's opinion might interfere with study objectives.
10. Contraindications to the use of Peg-IFNa-2a or incapable of self-administration or assisted administration of Peg-IFNa-2a (Peg-IFNa-2a enrolling arms)
11. Subjects with pre-existing ophthalmologic disorders (Peg-IFNa-2a enrolling arms)

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Cohort 1 (N=5): subjects will receive CLB-4000 (250 µg CLB-405 and 250 µg CLB-505 adjuvanted with 200 µg TQL-1055)

Cohort 3 (N=4): subjects will receive CLB-4000 (250 µg CLB-405 and 250 µg CLB-505 adjuvanted with 400 µg TQL-1055) with 180 µg Peg-IFNa-2a

Optional Cohort (N=up to 8) Following the review of available data by the safety review committee (SRC), in conjunction with an ongoing review of clinical activity by the Sponsor, an optional expansion of any one of, or a combination of, Cohorts 1 to 3, or a new cohort with a higher dose of TQL-1055 (up to 800 µg), may be considered. The first subject who receives CLB-4000 in each cohort or arm with a new dose level or combination will act as a sentinel subject.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/04/2025
Actual
Date of last participant enrolment
Anticipated
28/02/2027
Actual
Date of last data collection
Anticipated
29/02/2028
Actual
Sample size
Target
17
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27440 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 43552 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 318083 0
Commercial sector/Industry
Name [1] 318083 0
ClearB Therapeutics, Inc.
Country [1] 318083 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
ClearB Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 320439 0
None
Name [1] 320439 0
Address [1] 320439 0
Country [1] 320439 0
Other collaborator category [1] 283334 0
Commercial sector/Industry
Name [1] 283334 0
Novotech(Australia) Pty Limited
Address [1] 283334 0
Country [1] 283334 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316730 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 316730 0
Ethics committee country [1] 316730 0
Australia
Date submitted for ethics approval [1] 316730 0
06/01/2025
Approval date [1] 316730 0
20/03/2025
Ethics approval number [1] 316730 0
HREC 007/25

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

Contacts
Principal investigator
Name 138822 0
Prof Alexander Thompson
Address 138822 0
St Vincent's Hospital Melbourne, Director of Gastroenterology, 41 Victoria Parade, Fitzroy Victoria 3065, Australia
Country 138822 0
Australia
Phone 138822 0
+61 3 9231 3580
Fax 138822 0
Email 138822 0
[email protected]
Contact person for public queries
Name 138823 0
Alexander Thompson
Address 138823 0
St Vincent's Hospital Melbourne, Director of Gastroenterology, 41 Victoria Parade, Fitzroy Victoria 3065, Australia
Country 138823 0
Australia
Phone 138823 0
+61 3 9231 3580
Fax 138823 0
Email 138823 0
[email protected]
Contact person for scientific queries
Name 138824 0
Alexander Thompson
Address 138824 0
St Vincent's Hospital Melbourne, Director of Gastroenterology, 41 Victoria Parade, Fitzroy Victoria 3065, Australia
Country 138824 0
Australia
Phone 138824 0
+61 3 9231 3580
Fax 138824 0
Email 138824 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.