This study will examine the safety and tolerability of single and multiple doses of IB-001, and will be conducted in two parts:
Part A: SAD study in approximately 50 Healthy Volunteers (HV). Part B: MAD study in approximately 30 adult participants living with Chronic Hepatitis B (CHB).
Able and willing to provide written informed consent.
Male or female aged 18 to 70 years.
Females must not be of childbearing potential OR those who are of childbearing potential must be non-pregnant and non-lactating and willing to use a highly effective method of contraception. Males whose partners are of childbearing potential must either be surgically sterile or willing to use a highly effective acceptable method of contraception.
Non-tattooed, clear injection site suitable for SC injection and monitoring in the opinion of the Investigator.
Major surgery requiring general anesthesia within 12 weeks prior to Screening or is expected to have surgery requiring general anesthesia during the course of the study.
History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents.
Blood donation or blood loss of ≥ 1 unit (450 mL) of whole blood within 4 weeks before Screening or plasma donations within 7 days prior to dosing of investigational product (IP).
Any underlying medical condition (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrinological, tumor, pulmonary, immune, mental, or cardiovascular and cerebrovascular diseases).
Parallel
IB-001
DrugIB-001 is an investigational product targeting the type I IFN (IFN-I) signaling pathway. Subcutaneous (SC) injectable formulation; single doses in HVs (Part A) and weekly doses for 4 weeks in CHB participants (Part B). Exact dose levels recommended by SRC.
Placebo
Other interventionSodium Chloride (NaCl) 0.9 % administered subcutaneously as a single dose (Part A) and weekly dose for 4 weeks (Part B).
Part A and Part B: Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs).
Treatment-Emergent Adverse Events (TEAEs) are adverse events that first appear or worsen in severity during the course of the clinical study, regardless of whether they are related to the investigational product (IP) or not. TEAEs will be coded using MedDRA and summarized by SOC, PT, severity, and relationship to IP. Treatment-related AEs (possibly/probably/definitely related) will also be summarized separately. A by-participant AE listing will be provided
Part A and Part B: Number of Participants with Adverse Events (AEs) by Severity
An AE is any unfavorable medical occurrence in a study participant administered an investigational product. The AE does not necessarily have a causal relationship with the treatment. All AEs will be graded for severity according to NCI-CTCAE classification. If an appropriate AE term is not found in NCI-CTCAE, the AE will be graded as follows: Grade 1 (mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (Severe) and Grade 5 (Death).
Part A and Part B: Number of Participants with Adverse Events (AEs) of Special Interest (AESIs)
AEs of special interest include Cytokine Release Syndrome (CRS), Injection Site Reactions (ISRs) and Unexplained Liver Biochemistry Elevations. Reported AESIs will be graded according to NCI-CTCAE classification. If an appropriate AE term is not found in NCI-CTCAE, the AESI will be graded as follows: Grade 1 (mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (Severe) and Grade 5 (Death).
Part A and Part B: Number of Participants with Clinically Significant Changes in Laboratory Parameters
Assessment Method - Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, and coagulation) will be reported.
Part A and Part B: Number of Patients with Clinically Significant Anti-Drug Antibodies (ADAs).
All immunogenicity data (ADA) are to be analyzed using the Immunogenicity Analysis Population. ADA incidence and titer levels over time will be summarized by dose.
Part B: Changes from Baseline in HBsAg levels over time.
Blood samples will be analyzed for HBsAg levels to establish baseline and determine eligibility; subsequent blood samples will be collected at protocol-specified timepoints to measure HBsAg changes over time.
Part B: Change from Baseline in Anti-HBs Antibody Titers over time.
Blood samples will be collected at baseline and at protocol-specified timepoints to measure anti-HBs antibody titer changes over time.
Part B: Reduction from Baseline in HBV DNA levels over time.
Blood samples will be collected at baseline and at protocol-specified timepoints to measure HBV DNA changes over time.