Not Yet RecruitingPhase 1ACTRN12625000204448

Safety and Tolerability of CLB-4000 in Subjects with Chronic Hepatitis B: non-randomised cohorts

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

Sponsor

ClearB Therapeutics, Inc.

Enrollment

17 participants

Start Date

Apr 15, 2025

Study Type

Interventional

Conditions

Chronic Hepatitis B

Summary

Summary A Phase 1b Study Evaluating the Safety and Tolerability of CLB-4000 with or without Peg-IFNa-2a in Subjects with Chronic Hepatitis B Who is it for? You may be eligible for this study if you are an adult aged between 18 and 60 years old with chronic hepatitis B. Study details This is a Phase 1b, multicenter study designed to assess the safety and tolerability of repeated intramuscular (IM) administration of CLB-4000 (a fixed antigen concentration of 250 µg CLB-405 and 250 µg CLB-505, adjuvanted with multiple dose levels of TQL-1055) in noncirrhotic adults with CHB taking a stable dose of a standard of care nucleoside/nucleotide analogues (NUC) for viral suppression. To further boost the immune and antiviral responses, additional cohorts will evaluate CLB-4000 with Peg-IFNa-2a. Subjects with all HBV genotypes and either HBV-e antigen positive or negative status are included. CLB-4000 will be administered alone and in participants who will also receive Peg-IFNa-2a. Eligible participants will receive 5 monthly Intramuscular (IM) injections of CLB-4000 on Days 1, 30, 60, 90, and 120. Subjects participating in Peg-IFNa-2a arms of the study will self-administer or have a caregiver administer a weekly subcutaneous injection of Peg-IFNa-2a 180 mcg for 8 weeks during a run-in period and then for 16 weeks during the CLB-4000 treatment phase following injection training and instructions on proper storage and disposal by a clinician. The end of the study is defined as the last subject last visit at Day 300. The estimated duration of the study is approximately 11 months or, for subjects participating in Peg-IFNa-2a arms, 13 months.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria9

Able to give written informed consent.
Age 18 to 60 years, inclusive
Body mass index (BMI) 18 to 35 kg/m2.
Diagnosed with CHB for at least 6 months and a HBsAg greater than 100 IU/mL and less than 500 IU/mL..
Anti-HBs antibodies <2.0 IU/L.
Serum HBV DNA <20 IU/mL for more than equal to 6 months and HBV DNA <20 IU/mL at screening
Has received treatment with a NUC (entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide) for at least 6 months
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.
Male subjects must be surgically sterile, abstinent, agree to use an appropriate contraception.

Exclusion Criteria11

Participants with any evidence of liver disease of non-HBV etiology.
Previous history or current diagnosis of significant liver fibrosis or cirrhosis
History of or suspected hepatocellular carcinoma
Positive testing for HIV-1, HIV-2, HCV, or HDV that suggests a concurrent infection.
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).
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.
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.
History of anaphylaxis, hypersensitivity, or significant drug allergies.
Any condition that in the investigator's opinion might interfere with study objectives.
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)
Subjects with pre-existing ophthalmologic disorders (Peg-IFNa-2a enrolling arms)

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Interventions

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 cohor

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.