A Phase 1, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After a Single Dose and Multiple Doses in Healthy Subjects

INTERVENTION: Healthy subjects in Part 1 will receive a single oral liquid dose of DF‐006, starting at 3mcg, for one day. Subsequent doses will be based on safety data from prior patients and cohorts. The maximum dose that may be evaluated in Part 1 is 450 mcg. Healthy subjects in Part 2 will receive a single oral liquid dose of DF‐006 each day for 14 days, starting at the dose determined in Part 1. Participants in Part 2 are likely to be different from participants in Part 1. A Study Safety Committee will provide safety oversight and will follow Dose Selection Guidelines to determine cohort doses. Cohort progression will based on Data Review Meetings. In Part 1, cohort progression will occur approximately every 3 week. In Part 2, cohort progression will occur approximately every 4 weeks. Participants in Parts 1 and 2 and are both healthy volunteers. Adherence to the intervention will be monitored by direct observation of dosing. 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 DF‐006 by collecting adverse events, and monitoring lab results (hematology, biochemistry, coagulation and serum chemokine/cytokine), ECGs, and vital signs.; ; Adverse event will be initially reported based on subject reported events. These events will eventually be coded using MedRA codes.[Part 1: ; ‐Physical Examination, Vital Signs & ECG: Screening, Day ‐1 to Day 5; ‐Holter Monitoring: Day 1 & 2; ‐Biochemistry/Hematology/Coagulation: Screening, Day ‐1 to Day 5; ‐Chemokine/Cytokine: Day 1 & 2; ‐PBMC: Day 1 and 2 ; ‐Urinalysis: Screening, Day ‐1 to Day 5; ‐Plasma PK: Day 1 & 2; ‐Adverse Events: Continuous Assessment; ; Part 2:; ‐Physical Examination, Vital Signs & ECG: Screening, Day ‐1 to Day 28; ‐Biochemistry/Hematology/Coagulation: Screening, Day ‐1 to Day 28; ‐Chemokine/Cytokine: Day 1, 2, 7 and 15; ‐PBMC: Day 1 and 15; ‐Urinalysis: Screening, Day ‐1 to Day 28; ‐Plasma PK: Day 1, 2, 7 and 15; ‐Urine PK: Day 15; ‐Adverse Events: Continuous Assessment; ; Part 3:; ‐Physical Examination, Vital Signs & ECG: Screening, Day ‐7, 1, 2, 8, 15, 22, 29, 36, 43 & 50 ; ‐Biochemistry/Hematology/Coagulation: Screening, Day ‐7, 1, 2, 8, 15, 22, 29, 36, 43 & 50 ; ‐Chemokine/Cytokine: Day 1 & 15; ‐PBMC: Day 1 and 15; ‐Urinalysis: Screening, Day 1, 2, 8, 15, 22, 29, 36, 43 & 50 ; ‐Plasma PK: Day 1, 2 & 15; ‐Urine PK: Day 15; ‐HBV Genotype: Screening; ‐HBV DNA, HBV RNA, HBeAg, HBsAg, HBcrAg, HBsAg Antibody, HBeAg Antibody: Screening, Day ‐7, 2, 8, 15, 22, 29, 36, 43 & 50 ; ‐Adverse Events: Continuous Assessment] SECONDARY OUTCOME: Blood biomarkers: Chemokine levels will be measured for changes over time, [For Part 1: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Days 2 ; For Part 2: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14] Blood biomarkers: Cytokine levels will be measured for changes over time, [For Part 1: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Days 2 ; [For Part 1: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Day 2 ; For Part 2: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14] INCLUSION CRITERIA: Female subjects must have a negative serum pregnancy test and must not be of childbearing potential Male subjects must be either surgically sterile, or incapable of fathering a child, or have a heterosexual partner partner who is not pregnant or of childbearing potential Nonsmoker within last 3 months ; For Part 2: assessed on Day 1 (Hours: ‐1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14] To evaluate pharmacokinetics using the following parameters: AUC, Cmax, Cmin, T max, T1/2 . pharmacokinetics will be assessed using blood and urine samples. BMI of 18.0 to 32.0 kg/m2 Subjects must be deemed healthy by the Investigator on the basis of a medical evaluation