A Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Preliminary Efficacy and Pharmacodynamics of SM17 in Chinese Healthy Subjects and Patients With Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Incidence of treatment emergent AEs in each cohort(Ph1a)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Volunteers：
- •Male or Female，19~55 years old
- •BMI ≥18.5 and <28.0 kg/m² at the screening visit, with body weight ≥50 kg for males and ≥45 kg for females
- •Non-smokers or former smokers who have quit for at least 6 months, with a smoking history of <10 pack-years for former smokers at the screening visit. No history of alcohol consumption or light alcohol consumption prior to the screening visit.
- •No abnormalities or abnormalities of no clinical significance (NCS) in vital signs, physical examination, laboratory tests, or electrocardiogram (ECG) results during the screening period, QTcF <450 msec for male and QTcF <470 msec for female subjects.
- •Use one medically approved contraceptive method during the trial and for 6 months after the trial ends (specific methods see Appendix 1); No plans to donate sperm/ova during the trial and for 6 months after the trial ends.
- •informed consent.
- •Eligible patients must have a history of inadequate response or intolerance to treatment with topical AD medications.
- •Male or female, 18 ~70 years old
- •Atopic dermatitis (Hanifin & Rajka) at the screening visit with eczema symptoms reported over 1year
- •Eczema Area and Severity Index (EASI) score ≥16 at the screening and baseline visits
- •Investigator's Global Assessment (IGA) score ≥3 at the screening and baseline visits
- •≥10% body surface area (BSA) of AD involvement at the screening and baseline visits
- •Baseline pruritus numerical rating scale (NRS) weekly average score ≥4
- •Documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments are medically inadvisable (e.g. intolerance, because of important side effects, or safety risks)
- •Have applied a stable dose of topical bland emollient (moisturizer) at least twice daily for at least 7 consecutive days immediately before randomization
- •Willing and able to comply with all clinic visits and study-related procedures
- •Able to understand and complete study-related questionnaires
- •Signed written informed consent
排除标准
- •Healthy volunteers:
- •Presence of psychiatric or legal incapacity, significant emotional problems at the screening visit, or anticipation of such issues during the study period.
- •Regular alcohol consumption within 6 months prior to screening.
- •History or evidence of any clinically significant medical condition, situation, or disease.
- •Any laboratory parameter meeting the following criteria:
- •Total bilirubin (TBIL) >1.5 × upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × ULN
- •Serum creatinine (Cr) >1.5 × ULN
- •White blood cell count below the lower limit of normal (LLN), deemed clinically significant and unsuitable for inclusion by the investigator at screening or baseline.
- •History or current diagnosis of cardiovascular/cerebrovascular disease.
- •Prior hospitalization for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.
- •Evidence of any active or suspected bacterial, viral, fungal, or parasitic infection within 4 weeks prior to screening. Subjects deemed at high risk for parasitic diseases are also excluded.
- •Known diagnosis of Type I/II diabetes mellitus or prediabetes.
- •Administration of live (attenuated) vaccines within 1 month prior to first dose.
- •History of any malignancy within 5 years prior to screening (except successfully treated carcinoma in situ of the cervix or surgically excised non-melanoma skin cancer).
- •Any known history of primary or secondary immunodeficiency disorders.
- •Positive drug urine screen or alcohol consumption within 48 hours prior to screening.
- •History or presence of hypersensitivity or idiosyncratic reactions to protein therapies, drugs, any component of SM17, or related compounds.
- •Active infection including: Tuberculosis (TB), Hepatitis B, Hepatitis C, Human Immunodeficiency Virus.
- •Use of any prescription or non-prescription medication within 14 days or 5 half-lives (whichever longer) prior to first SM17 dose.
- •Tattoos, scars at/near the infusion site, or any other condition potentially interfering with infusion site examination, per investigator assessment.
- •Blood/plasma donation (≥500 mL) or significant blood loss within 2 months prior to screening; planned donation during study. Bone marrow donation within 3 months prior to first dose.
- •Inability to undergo protocol-required visits/procedures per investigator/subject knowledge.
- •Current/recent participation in another investigational drug/device study.
- •AD patients:
- •Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
- •Laboratory abnormality for serum hemoglobulin, WBC, neutrophils, platelet, ALT/AST, TBIL, serum creatinine at screening or baseline
- •HIV/HBV/HCV/TB positive
- •ECG abnormality with clinical significance
- •History of concomitant diseases: VKC/AKC, other skin diseases, active chronic or acute infection requiring treatment with systemic medications, malignancy within 5 yrs, other major diseases
- •History of acute allergies, or known allergies to composition of monoclonal antibodies or excipients
- •Treatments within 4 weeks before the baseline visit, or is likely to require such treatment(s) during the study treatment:
- •systemic corticosteroids, Janus kinase inhibitors
- •other immunosuppressive/immunomodulating drugs (cyclosporine, mycophenolate-mofetil, IFN-γ,, azathioprine, MTX..)
- •traditional Chinese medicine
- •Treatment with TCS, TCI, PDE-4 inhibitor, or other topical AD medications within 1 week before baseline
- •New treatment of anti-histamine or ICS within 1 week before baseline ( stable doses of anti-histamine or ICS is allowed during study)
- •Treatment with biologics, within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer
研究组 & 干预措施
SAD cohort 1
single ascending dose cohort 1, participants(HVs) will receive 70mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 for injection (Drug)
SAD cohort 1
single ascending dose cohort 1, participants(HVs) will receive 70mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 placebo for injection (Other)
SAD cohort 2
single ascending dose cohort 2, participants(HVs) will receive 200mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 for injection (Drug)
SAD cohort 2
single ascending dose cohort 2, participants(HVs) will receive 200mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 placebo for injection (Other)
SAD cohort 3
single ascending dose cohort 3, participants(HVs) will receive 600mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 for injection (Drug)
SAD cohort 3
single ascending dose cohort 3, participants(HVs) will receive 600mg of SM17 or placebo intravenously in this cohort with randomization ratio 6:2
干预措施: SM17 placebo for injection (Other)
MD cohort
multiple doses cohort, participants(HVs) will receive consecutive doses of 600mg of SM17 or placebo intravenously, once every 2 weeks in this cohort with randomization ratio 6:2
干预措施: SM17 for injection (Drug)
MD cohort
multiple doses cohort, participants(HVs) will receive consecutive doses of 600mg of SM17 or placebo intravenously, once every 2 weeks in this cohort with randomization ratio 6:2
干预措施: SM17 placebo for injection (Other)
SM17 lower dose group
treatment group for participants (AD patients) to receive lower consecutive dose of SM17 （200mg）intravenously once every 2 weeks until end of treatment
干预措施: SM17 for injection (Drug)
SM17 higher dose group
treatment group for participants (AD patients) to receive higher consecutive dose of SM17 （200mg）intravenously once every 2 weeks until end of treatment
干预措施: SM17 for injection (Drug)
placebo group
control group for participants (AD patients) to receive placebo doses intravenously once every 2 weeks until end of treatment
干预措施: SM17 placebo for injection (Other)
结局指标
主要结局
Incidence of treatment emergent AEs in each cohort(Ph1a)
时间窗: Day 0 to Day85 (SAD cohorts), Day 0 to Day 113 (MD cohort)
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.
Incidence of Treatment emergent AEs (TEAEs) in each treatment group(ph1b)
时间窗: Week 0 to Week 16
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
次要结局
- Area under the plasma concentration versus time curve (AUC) in Chinese healthy volunteers(12 weeks following SM17 dose （SAD） or last dose （MD）)
- Immunogenicity(Week 0~16)
- Area under the plasma concentration versus time curve (AUC) in Chinese AD patients(Week 0 (baseline) to Week 16)
- Efficacy for treating AD - EASI50%(Week12, Week 16)
- Efficacy for treating AD-EASI75%(Week12, Week 16)
- Efficacy for treating AD-EASI90%(Week12, Week 16)
- Efficacy for treating AD-EASI score change(Week2,4,6,8,10,12,16)
- Efficacy for treating AD-IGA 0/1%(Week12, Week16)
- Efficacy for treating AD- PP-NRS(Baseline (Week0) to Week 16)
- Efficacy for treating AD-NRS-4%(Week2，4，6，8，10，12，16)
- Efficacy for treating AD-BSA%(Week 2，4，6，8，10，12，16)
- Efficacy in treating AD-SCORAD(Week 4，8，10，12，16)
- Efficacy for treating AD-POEM(Week2，4，6，8，10，12，16)
- Efficacy for treating AD-DLQI(Week2,4,6,8,10,12,16)