A Phase 1, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Doses in Chronic Hepatitis B subjects

INTERVENTION: This is a double‐blind, randomized, placebo‐controlled, multiple‐ascending doses (MAD) study that will be conducted in up to 120 chronic hepatitis B (CHB) subjects. Hepatitis B e‐antigen (HBeAg)‐negative virologically suppressed (VS), HBeAg‐negative treatment naïve (TN), or currently untreated (CU) CHB subjects with abnormal serum alanine aminotransferase (ALT), and HBeAg‐positive TN or CU CHB subjects with normal serum ALT will be evaluated in separate MAD cohorts of up to 40 subjects each. This study will investigate the safety, tolerability, PD, and antiviral activity of once weekly (QW) oral (PO) doses of DF‐006 for 4 weeks. Subject follow‐up will occur for 4 weeks after administration of the last dose of study drug. Subsequent cohort dosage (multiple‐ascending doses) and dosing frequency will be based on Dose Selection Guidelines and prior cohort CHB subject data. Three cohorts of HBeAg‐negative VS CHB subjects of 8 subjects each (24 subjects in total), and up to 2 optional cohorts of 8 subjects each (16 subjects in total), will receive once QW PO doses of DF‐006 or matching placebo for a duration of 4 weeks. Within each cohort, 6 subjects will be randomly assigned to receive DF‐006, and 2 subjects will receive matching placebo. Three cohorts of HBeAg‐negative TN/CU CHB subjects with abnormal serum ALT of 8 subjects each (24 subjects in total), and up to 2 optional cohorts of 8 subjects each (16 subjects in total) will receive PO QW doses of DF‐006 or matching placebo for a duration of 4 weeks. Within each cohort, 6 subjects will be randomly assigned to receive DF‐006, and 2 subjects will receive matching placebo. Three cohorts of HBeAg‐positive TN/CU CHB subjects with normal serum ALT of 8 subjects each (24 subjects in total), and up CONDITION: Chronic Hepatitis B; ; Chronic Hepatitis B Infection ‐ Other infectious diseases Oral and Gastrointestinal ‐ Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon PRIMARY OUTCOME: Safety and tolerability of multiple doses of DF‐006 in CHB patients will be assessed by collecting adverse events and monitoring lab results (hematology, biochemistry, coagulation and serum chemokine/cytokine), ECGs, and vital signs.; ; Adverse events will be initially reported based on subject reported events. These events will eventually be coded using MedDRA codes.; [ Safety and tolerability of multiple doses of DF‐006 in CHB patients will be assessed as follows at the specified time points.; ; ‐Physical Examination, Vital Signs & ECG: Screening, Days ‐7, 1, 4 8, 11, 15, 22, 29, 36, 43 & 50; ‐Biochemistry/Hematology/Coagulation: Screening, Days ‐7, 1, 4, 8, 15, 22, 29, 36, 43 & 50; ‐Chemokine/Cytokine: Days 1, 4, 8, 11, & 15; ‐PBMC: Days 1 and 29; ‐Urinalysis: Screening, Days 1, 4, 8, 15, 22, 29, 36, 43 & 50; ‐Plasma PK: Day 1, 4 & 15; ‐Urine PK: Day 15; ‐HBV Genotype: Screening for HBV DNA, HBV RNA, HBeAg, HBsAg, HBcrAg, HBsAg Antibody, HBeAg Antibody: Screening, Day ‐7, 4, 8, 15, 22, 29, 36, 43 & 50; ‐Adverse Events: Continuous Assessment from the first dose of study drug until end of follow‐up period after last dose of study drug. Subject follow‐up will occur for 4 weeks after administration of the last dose of study drug.; ] SECONDARY OUTCOME: Blood biomarkers: Chemokine levels will be measured for changes over time. This will be assessed in all patients receiving multiple doses of study drug.[ Assessed on Day 1 ( Hours: ‐1, 1, 2) and once on Days 4,8,11,15,18,22,25,29,36,43,50 in all patients receiving multiple doses of study drug.] To evaluate pharmacokinetics of multiple doses of DF‐006 in CHB patients, the following parameters: AUC, Cmax, Cmin, T max, T1/2 . pharmacokinetics will be assessed using blood and urine samples. [ Assessed on Day 1 ( Hours: ‐1, 1, 2) and once on Days 4,8,11,15,18,22,25,29,36,43,50 in all patients receiving multiple doses of study drug.] INCLUSION CRITERIA: 1) Subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. 2) In the Investigator’s opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned. 3) Female subjects must NOT be of childbearing potential, which is defined as postmenopausal or permanently sterile, OR, if they are a woman of childbearing potential (WOCBP), must agree to use a condom and/or highly effective contraceptive therapy. 4) Male subjects must be either surgically sterile (eg, had a vasectomy), or otherwise incapable of fathering a child; OR, if non‐sterile and heterosexually active, must have a partner who is postmenopausal, surgically sterile; OR, if their partner is WOCBP, must use highly effective methods of contraception from the time of