A First-in-human Study of APG777 in Healthy Participants

INTERVENTION: IP Name: APG777 Treatment: Drug – APG777 Treatment Drug – Placebo Single ascending dose (SAD) Cohorts 1. Cohort 1: APG777 (Low dose) or Placebo ‐ Participants will receive single subcutaneous (SC) injection of low dose (300 mg) of APG777 or placebo 2. Cohort 2: APG777 (Medium dose) or Placebo – Participants will receive single subcutaneous injection of medium dose (600 mg) of APG777 or placebo 3. Cohort 3: APG777 (High dose) or Placebo ‐ Participants will receive single subcutaneous injection of high dose (1200 mg) of APG777 or placebo Study drug will be administered as a subcutaneous (SC) injection by trained personnel at the clinical research unit (CRU) and administration will be noted in patient medical records. Multiple dose (MD) Cohorts 1. Cohort 1: Participants will receive 300 mg of APG777 or placebo by subcutaneous injection on Day 1 and Day 29 2. Cohort 2: Participants will receive 300 mg of APG777 or placebo by subcutaneous injection on Day 1 and Day 15 Study drug will be administered as a SC injection by trained personnel at the CRU. The first MD cohort will be enrolled after the SRC has reviewed a minimum of 14 days post dose (Day 15) of safety and PK data from the SAD cohort. Approval of the MD part of the study is subject to HREC submission and approval. CONDITION: Atopic Dermatitis; ; Atopic Dermatitis Skin ‐ Dermatological conditions PRIMARY OUTCOME: SAD/MD Cohort: To evaluate the safety and tolerability of APG777; ‐ Incidence of Treatment Emergent Adverse Events (TEAEs) coded based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. ; ‐ Incidence of clinically significant laboratory findings (Chemistry using serum, Hematology. Urinalysis) ; ‐ Incidence of clinically significant vital signs include heart rate through stethoscope, blood pressure through digital Sphygmomanometer, body temperature, and respiratory rate ; ‐ Incidence of clinically significant changes in electrocardiograms; [SAD Cohorts:; Day ‐1 (pre‐treatment), and post initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337. ; ; MD (Day 1 and Day 29 dosing): ; Day ‐1 (pre‐treatment), and post‐initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 28. Post initiation of 2nd treatment on Day 29, Day 30, Day 36, Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337.; ; MD (Day 1 and Day 15 dosing): Day ‐1 (pre‐treatment), and post‐initiation of treatment on Day 1, Day 2, Day 3, Day 4, Day 8, Day 14. Post initiation of 2nd treatment on Day 15, Day 16, Day 22, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253 and Day 337. ; ] INCLUSION CRITERIA: • Healthy men and women, as determined by physical examination, laboratory screening tests, and medical history • Body mass inde X(BMI) of 18 to 35 kg/m2 (inclusive), weight less than 120 kg • Willing to use a highly effective method of contraception from admission through 12 months or 5 half‐lives, whichever is longer, after the last administration of study drug SECONDARY OUTCOME: SAD/MD Cohort: Number of participants with antibodies to APG777 ; Serum samples will be collected for analysis of immunogenic response to determine presence/absence and titers of anti‐drug antibodies ; [SAD Cohorts ; Post‐dose on Day 1 (0h), Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, Day 337. ; ; MD (Day 1 and Day 29 dosing) ; Post‐dose on Day 1 (0h), Day 15, and Day 22. ; Post‐dose on Day 29 (0h), Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337. ; ; MD (Day 1 and Day 15 dosing) ; Post‐dose on Day 1 (0h). ; Post‐dose on Day 15 (0h), Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337. ; ] SAD/MD Cohort: To characterize the single dose and multi‐dose PK of APG777 ; Blood samples will be collected from all participants. ; Parameters: ; ‐ Maximum observed concentration (Cmax) ; ‐ Time to reach Cma X(Tmax) ; ‐ Apparent first‐order terminal elimination rate constant ; ‐ Apparent first‐order terminal elimination half‐life ; ‐ The area under the concentration‐time curve from time 0 to the last observed non‐zero concentration ; ‐ The area under the concentration‐time curve from time 0 extrapolated to infinity. ; ‐ Apparent total clearance after administration ; ‐ Apparent volume of distribution during the terminal elimination phase after administration ; [SAD Cohorts ; Day 1 (less than 1hr prior to dose), and post‐dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), Day 4 (72 h ± 4 h) and on Day 8, Day 15, Day 22, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337. ; ; MD (Day 1 and Day 29 dosing) ; Day 1 (less than 1hr prior to dose), and post‐dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), and on Day 8, Day 15, and Day 22. ; Day 29 (less than 1hr prior to dose), and post‐dose on Day 29 (4 h ± 30 min, 8 h ± 1 h), Day 30 (24 h ± 2 h), Day 36, Day 43, Day 50, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337. ; ; MD (Day 1 and Day 15 dosing) ; Day 1 (less than 1hr prior to dose), and post‐dose on Day 1 (4 h ± 30 min, 8 h ± 1 h), Day 2 (24 h ± 2 h), Day 3 (48 h ± 2 h), Day 4 (72 h ± 2 h), Day 8, and Day 14. ; Day 15 (less than 1hr prior to dose), and post‐dose on Day 15 (4 h ± 30 min, 8 h ± 1 h), Day 16 (24 h ± 2 h), Day 22, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 253, and Day 337. ; ]