This is a phase I study in Chinese healthy adult volunteer participants. It aims to evaluate the safety, tolerability, PK profile and immunogenicity of a single dose of SM17 SC in healthy Chinese adult participants. It also aims to evaluate the bioavailability of SM17 SC compared to SM17 IV.
This Phase I study will be conducted in Chinese healthy adult participants to evaluate the safety, tolerability, PK, and immunogenicity of SM17 SC. This study plans to enroll a total of 30 healthy participants across 4 cohorts, among which three cohorts (n = 8 per cohort) will receive SM17 via subcutaneous injection (SC cohorts), and one cohort (n = 6) will receive SM17 via intravenous injection (IV cohort). SM17 SC cohorts: This part is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study. A total of 24 healthy participants will be enrolled into three SC cohorts (A1 to A3), with dose levels of 195 mg, 390 mg, and 780 mg, respectively. Each cohort will enroll 8 healthy participants. Each participant will receive a single SC dose of either SM17 (n = 6) or placebo (n = 2). SM17 IV cohort: This part is an open-label, single-dose study. Six healthy participants will be enrolled in a single IV cohort (Cohort B) and will each receive a single intravenous injection of SM17 at a dose of 390 mg. The SM17 SC A2 cohort and SM17 IV cohort (Cohort B) will be enrolled in parallel, and participants will be randomized to one of the two cohorts. A dedicated Safety Review Committee (SRC) will be established for this study. The SRC is responsible for deciding whether to proceed to the next dose cohort based on a review of all relevant safety data from participants at the current dose level for at least 7 days after dosing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
SM17 monoclonal antibody
placebo to be compared with SM17, excipient solution of SM17 monoclonal antibody without protein
PKUCare Luzhong Hospital
Zibo, Shandong, China
Incidence of treatment emergent AEs
To evaluate the safety and tolerability of SM17 in Chinese healthy volunteers administrated with single dose of SM17 or placebo intravenously. Treatment emergent AE was any unfavorable or unintended medical occurrence in each subject, including any abnormal changes in vital signs or lab testing with clinical significance judged by investigators, that happened during the period of receiving or after receiving the investigational product, categorized by type, severity, and causality with the study drug
Time frame: Day 0 to Day 85
Area under the plasma concentration versus time curve (AUC)
To evaluate the PK parameter(AUC), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Peak Plasma Concentration (Cmax)
To evaluate the PK parameter(Cmax), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Time to peak (Tmax)
To evaluate the PK parameter(Tmax), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Elimination half-life (T1/2)
To evaluate the PK parameter(T 1/2), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
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Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Elimination Rate Constant (Kel)
To evaluate the PK parameter(Kel), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Total drug clearance from plasma (CL)
To evaluate the PK parameter(CL), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Apparent volume of distribution at steady state after extravascular administration (Vz)
To evaluate the PK parameter(Vz), which calculated from serum SM17 concentration, of a single dose of SM17 in healthy Chinese adult participants.
Time frame: Day1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 43, 57, 85(Cohort A1, Cohort A2, Cohort A3); Day1, 2, 3, 4, 6, 8, 15, 29, 43, 57, 85(Cohort B).
Immunogenicity
To evaluate the immunogenicity of SM17 in adult healthy participants. Incidence of treatment emergent anti-drug antibodies (ADAs) during the study.
Time frame: Day1, 15, 29, 85