A Phase Ib, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of M5049 Administered Orally in SLE and CLE Participants Treated With Standard of Care
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 12
- 主要终点
- Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity
研究概览
简要总结
This study is to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered M5049 in participants with systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Active systemic lupus erythematosus (SLE) with a Cutaneous lupus erythematosus disease area and activity index (CLASI-A) greater than or equal to [>= ] 6 and/or at least one active SLE clinical manifestation according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
- •Active cutaneous lupus erythematosus (CLE) (subacute cutaneous lupus erythematosus and/or discoid lupus erythematosus) with a CLASI-A >= 6
- •Other protocol defined inclusion criteria could apply
排除标准
- •Autoimmune or rheumatic disease other than SLE or CLE
- •Dermatological diseases other than cutaneous manifestations of SLE or CLE
- •Uncontrolled medical conditions including significant cardiovascular events, active lupus nephritis, and active neurological disorder
- •Ongoing or active clinically significant viral, bacterial or fungal infection
- •History of uncontrolled seizures or other neurological disorder
- •History of or positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
- •History of malignancy
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Part A (Cohort 1): M5049 Dose A
干预措施: M5049 (Drug)
Part A (Cohort 2): M5049 Dose B
干预措施: M5049 (Drug)
Part A (Cohort 3): M5049 Dose C
干预措施: M5049 (Drug)
Part A (Cohort 4): M5049 Dose D
干预措施: M5049 (Drug)
Part A: Placebo
干预措施: Placebo (Drug)
Part B (Cohort 5): M5049 Dose E
干预措施: M5049 (Drug)
Part B: Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity
时间窗: Up to Day 186
Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings
时间窗: Up to Day 186
Part A: Cohort 1 and 2: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure
时间窗: Up to Day 102
Part A: Cohort 1 and 2: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings
时间窗: Up to Day 102
Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs
时间窗: Up to Day 102
Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs
时间窗: Up to Day 186
Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity
时间窗: Up to Day 102
Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure
时间窗: Up to Day 186
Part A: Cohort 1 and 2: Number of Participants with Suicidal Behavior and Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Day 102
次要结局
- Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049(Day 1 and Day 29)
- Part A and Part B: Total Body Clearance (CL/f) of M5049(Day 1)
- Part A and Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5049(Day 1 and Day 29)
- Part A and Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049(Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc Cmax) of M5049(Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049(Day 29)
- Part A and Part B: Apparent Volume of Distribution (Vz/f) of M5049(Day 1)
- Part A and Part B: Change from Baseline in 28-Joint Count(Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M5049(Day 1 and Day 29)
- Part A and Part B: Elimination Rate Constant (Lambda z) of M5049(Day 1 and Day 29)
- Part A and Part B: Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Activity Index (CLASI-A)(Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)(Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of M5049(Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5049(Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Change from Baseline in Physician Global Assessment (PGA) Score(Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B)
- Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours Post-Dose (AUC0-12h) of M5049(Day 29)
- Part A and Part B: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049(Day 1)
- Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M5049(Day 1)