This trial is a phase 1, randomized, double-blind, placebo-controlled trial conducted in Chinese Healthy Volunteers and Patients with moderate-to-severe Atopic Dermatitis It aims to evaluate the safety, tolerability, pharmacokinetic characteristics and immunogenicity of single and multiple doses of SM17 injection in healthy subjects . It also aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect and immunogenicity as well as preliminary efficacy in AD patients.
This trial consists of 2 parts: Part 1 (Ph1a) trial of the study is a dose-ascending study to evaluate the safety, tolerability, pharmacokinetic characteristics of SM17 in Chinese healthy volunteers. Safety and PK profiles of SM17 in Chinese population will be established firstly in this study following single and multiple doses of SM17 injection, and possible differences to those of SM17 in US populations will also be evaluated. Part2 (ph1b) trial of the study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and preliminary efficacy of SM17 in treating patients with moderate-to-severe atopic dermatitis(AD) following multiple doses of SM17 injections at two doses level of SM17 or placebo. PK/PD profiles, immunogenicity profile of SM17 in AD patients will also be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
SM17 monoclonal antibody for intravenous infusion use
placebo to be compared with SM17, excipient solution of SM17 monoclonal antibody without protein
The First Hospital of China Medical University
Shenyang, Liaoning, China
Incidence of treatment emergent AEs in each cohort(Ph1a)
Safety and tolerability of SM17 in Chinese healthy volunteers administrated with 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.
Time frame: Day 0 to Day85 (SAD cohorts), Day 0 to Day 113 (MD cohort)
Incidence of Treatment emergent AEs (TEAEs) in each treatment group(ph1b)
Safety and tolerability of SM17 in Chinese AD patients administrated with 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. changes in vital signs and lab testing
Time frame: Week 0 to Week 16
Area under the plasma concentration versus time curve (AUC) in Chinese healthy volunteers
Serum Pharmacokinetic (PK) parameter of SM17 in Chinese healthy subjects administrated with SM17 intravenously
Time frame: 12 weeks following SM17 dose (SAD) or last dose (MD)
Immunogenicity
ADA positive rate in Chinese healthy volunteers
Time frame: Baseline to 12 weeks following SM17/placebo dose (SAD) or last dose(MD)
Area under the plasma concentration versus time curve (AUC) in Chinese AD patients
Pharmacokinetic parameter obtained from Chinese patients with moderate-to-severe AD administrated with SM17 intravenously
Time frame: Week 0 (baseline) to Week 16
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Efficacy for treating AD - EASI50%
Portion of participants reaching response as EASI50(A 50% decrease in Eczema Area and Severity Index, which ranges from 0\~72, and a deeper decrease means better outcome) in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously
Time frame: Week12, Week 16
Efficacy for treating AD-EASI75%
Portion of participants reaching response as EASI75(A 75%50% decrease in Eczema Area and Severity Index, which ranged from 0\~72, and a deeper decrease means better outcome) in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously
Time frame: Week12, Week 16
Efficacy for treating AD-EASI90%
Portion of participants reaching response as EASI90(a 90% decrease in Eczema Area and Severity Index, which ranges from 0\~72, and a deeper decrease means better outcome) in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously
Time frame: Week12, Week 16
Efficacy for treating AD-EASI score change
EASI(Eczema Area and Severity Index) score(ranges 0\~72,higher score means worse disease condition) change from baseline and percentage change from baseline in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously
Time frame: Week2,4,6,8,10,12,16
Efficacy for treating AD-IGA 0/1%
Portion of participants reaching response as IGA 0/1 in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously. Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™) score ranges from 0 to 4, with lower scores indicating less severe AD. IGA 0/1 is defined as scores of 0 or 1, indicating a clear or almost clear AD presentation, and with at least 2-point reduction from baseline at time of assessment.
Time frame: Week12, Week16
Efficacy for treating AD- PP-NRS
Change from baseline and Percentage change from baseline in PP-NRS weekly average score. PP-NRS is peak pruritus numeric rating scale, ranges 0\~10, with higher score indicating a more severe itch condition. PP-NRS is assessed by patients to evaluate the peak pruritus condition for the past 24 hrs. A weekly average score is calculated as mean value of PP-NRS scores of 7 consecutive days prior to the point of assessments (need at least scores from 4/7 days available required to get a valid weekly average score).
Time frame: Baseline (Week0) to Week 16
Efficacy for treating AD-NRS-4%
Portion of participants reaching response as NRS-4 in Chinese patients with moderate-to-severe AD administrated with SM17 intravenously. PP-NRS is peak pruritus numeric rating scale, ranges 0\~10, with higher score indicating a more severe itch condition. NRS-4 is defined as at least 4 points reduction from baseline in weekly average score of PP-NRS. A weekly average score baseline is calculated as mean value of PP-NRS scores of 7 consecutive days prior to treatments (need at least scores from 4/7 days available to get a valid weekly average score baseline).
Time frame: Week2,4,6,8,10,12,16
Efficacy for treating AD-BSA%
Change from baseline in Body Surface Area%(BSA%) with AD involvement, with a larger BSA% indicating a more severe disease condition.
Time frame: Week 2,4,6,8,10,12,16
Efficacy in treating AD-SCORAD
Change from baseline and percentage change from baseline in SCORAD (SCORing Atopic Dermatitis), ranges 0\~103, with higher score indication a worse disease condition.
Time frame: Week 4,8,10,12,16
Efficacy for treating AD-POEM
Change from baseline and Percentage change from baseline in POEM (Patient-Oriented Eczema Measure scores, range 0-28), with higher score indicating a worse disease condition.
Time frame: Week2,4,6,8,10,12,16
Efficacy for treating AD-DLQI
Change from baseline in DLQI score (Dermatology Life Quality Index, range 0\~30, with higher score indicating a higher disease burden).
Time frame: Week2,4,6,8,10,12,16
Immunogenicity
ADA positive rate in Chinese patients with moderate-to-severe AD treated by SM17/placebo intravenously
Time frame: Week 0~16