A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CB06-036 in Subjects With Chronic Hepatitis B

Exclusion Criteria

• •1\. CHB patients with extensive bridging fibrosis or cirrhosis (METAVIR ≥3 or Ishak ≥4 by a liver biopsy within 5 years, FibroTest score \>0.48 and APRI \>1, or a historic FibroScan \>9 kPa within 6 months prior to screening).
• •2\. Subjects met any of the following laboratory parameters at screening:
• •1. hemoglobin \<12 g/dL (for males) or \<11 g/dL (for females)
• •2. white blood cell count \<2500 cells/mm3 Protocol CONFIDENTIAL Labcorp Drug Development Study: 000000244098 Protocol Reference: CB06-036-102 Protocol Version 1.0, 24 January 2023 Page 8 of 68
• •3. neutrophil count \<1500 cells/mm3 (or \<1000 cells/mm3 if considered a physiological variant in a subject of African descent)
• •4. ALT \>2 × ULN
• •5. INR \>ULN unless the subject is stable on an anticoagulant regimen affecting INR
• •6. albumin \<3.5 g/dL
• •7. direct bilirubin \>1.5 × ULN
• •8. platelet Count \<100,000/μL
• •9. estimated creatinine clearance (CrCl) \<60 mL/min (using the Cockcroft-Gault method).
• •3.Active systemic infections (other than common cold) within 2 weeks before randomization.
• •4.At screening, known history of lymphoma, leukemia, or malignancy within the past 5 years, except for squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• •5.History or suspicion of hepatocellular carcinoma (ie, elevated alpha fetoprotein (AFP) \>50 ng/mL; suggestive lesions on abdominal ultrasound or other imaging).
• •6.History or presence of a medical condition associated with liver disease other than HBV infection (eg, hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, moderate to severe nonalcoholic steatohepatitis). Other known clinically significant hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• •7.History of transaminase (ALT and/or AST) flare in the previous 6 months prior to study enrollment.
• •8.Personal or familial history or symptomatology indicative of a risk of immune mediated disease (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, autoimmune uveitis, multiple sclerosis).
• •9.Received a solid organ or bone marrow transplant. 10.Received prolonged systemic therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, interferon) within 3 months of screening.
• •11.Blood donation of approximately 500 mL within 56 days prior to first administration of study drug, plasma from 2 weeks prior to screening, or platelets from 6 weeks prior to screening.
• •12.Have a known history of asthma. Note: Subjects with resolved childhood asthma with no history of hospitalization due to asthma are allowed.
• •13.Current use of strong and moderate CYP3A4 inhibitors or inducers; please see Appendix 6 for a list.
• •14.Are currently enrolled in, or discontinued from, a clinical trial involving an investigational product or non-approved drug within the last 4 weeks or at least 5 half-lives of the last dosing, if the half-life of the investigational product or non-approved drug is greater than 5 days; or concurrently enrolled in any other types of medical research judged not to be scientifically or medically compatible with this study.
• •15.live vaccination during the course of the study, or have participated in a vaccine clinical trial within 12 weeks prior to randomization. Investigators should review the vaccination status of the subjects and follow the local guidelines for adult vaccination with non-live vaccines intended to prevent infectious disease prior to administration of study drug.
• •16.Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV).
• •• Subjects who are HCV Ab positive, but have a documented negative HCV RNA, are eligible.
• •17.Abnormal clinical laboratory values at screening that, in the opinion of the investigator, pose an unacceptable risk to the subject or of interfering with the interpretation of study results if participating in the study.
• •18.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test at screening or at Days -7 to -4.
• •19.Have any other condition that precludes the subject from following and completing the protocol in the opinion of the investigator.
• •20.Significant history or clinical manifestation of any metabolic, allergic, dermatologic, hepatic, renal, hematologic, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, retinal, or psychiatric disorder, as determined by the investigator (or designee).
• •21.History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
• •22.Use or intend to use any nonprescription medications or products including vitamins, minerals, and herbal supplements (ie, traditional Chinese medicine), protein powders or fish oils preparations within 7 days prior to screening, considered to potentially impact subject safety or the objectives of the study, as determined by the investigator (or designee).
• •23.Alcohol consumption of \>21 units per week for males and \>14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
• •24.Ingestion of Seville orange or grapefruit-containing foods or beverages within 7 days prior to screening.