A 4-part Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of M254 in Healthy Volunteers and in Patients With Immune Thrombocytopenic Purpura
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 28
- 主要终点
- Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values
研究概览
简要总结
The purpose of this study is to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of M254 after administration of a single ascending dose and repeat doses in healthy volunteers and immune thrombocytopenic purpura (ITP) patients. The pharmacodynamics of the drug will be measured as platelet response in patients with ITP.
详细描述
The Part A of the study is currently not accepting healthy volunteers as the recruitment for the part A has completed.
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
- None
盲法说明
Part A: Double (Subject, Investigator);
Part B, C, and D: Open Label Investigations
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A
Healthy volunteers will receive a single ascending dose of M254 or placebo
干预措施: Placebo (Drug)
Part B
Immune thrombocytopenic purpura (ITP) patients will receive a single ascending dose of M254 followed by IVIg
干预措施: Intravenous immunoglobulin (IVIg) (Biological)
Part C
ITP patients will receive a single dose of M254 or IVIg, followed by a single dose of the other drug approximately 28 days later
干预措施: Intravenous immunoglobulin (IVIg) (Biological)
结局指标
主要结局
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values
时间窗: From Day 1 up to Day 29
Number of participants with clinically significant laboratory abnormalities (chemistry, hematology, urinalysis and coagulation) were reported. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A.
Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
时间窗: From Day 1 up to Day 29
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A TEAE was defined as any event not present prior to administration of the study drug or any event already present that worsened in either severity or frequency following exposure to the study drug. Severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. For Parts B and C, treatment period wise AE data were presented.
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs
时间窗: From Day 1 up to Day 29
Number of participants with clinically significant abnormalities in vital signs (blood pressure \[systolic blood pressure {SBP} and diastolic blood pressure {DBP}\], pulse rate, respiratory rate, and body temperature) were reported. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A.
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs)
时间窗: From Day 1 up to Day 29
Number of participants with clinically significant abnormalities in ECGs were reported. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A.
Part C: Maximum Observed Response of M254 (Rmax) on Platelet Count
时间窗: Predose (baseline) up to Day 29 post dose
Rmax is defined as the maximum observed response of M254 on platelet count. Baseline was the pre-dose sample. Data was planned to be collected and analyzed Part C only. For Part C, data were collected and analyzed on the pooled population per the study drug (M254 120 mg/kg and IVIg 1000 mg/kg) which the participants received.
Part C: Change From Baseline in Rmax of M254 in Platelet Count
时间窗: Predose (baseline) up to Day 29 post dose
Change from baseline in Rmax of M254 in platelet count was reported. Rmax is defined as the maximum observed response of M254. Baseline was the predose sample. Therapeutic platelet count was defined as \>=50\*10\^9 cells/L. Platelet response of \>=20\*10\^9 cells/L was considered as increase from baseline. Data was planned to be collected and analyzed for Part C only. For Part C, data were collected and analyzed on the pooled population per the study drug (M254 120 mg/kg and IVIg 1000 mg/kg) which the participants received.
Part C: Area Under Effect Curve of the Change From Baseline in Platelet Count From Day 0 to Day 28 (AUEC[0-Day 28]) of M254
时间窗: Predose (baseline) up to Day 29 post dose
AUEC(0-Day 28) is defined as the area under effect curve of the change from baseline in platelet count from Day 0 to Day 28 of M254. Baseline was the predose sample. Data was planned to be collected and analyzed for Part C only. For Part C, data were collected and analyzed on the pooled population per the study drug (M254 120 mg/kg and IVIg 1000 mg/kg) the participants received.
Part C: Area Under Effect Curve of the Change From Baseline in Platelet Count From Day 0 to Day 14 (AUEC[0-Day 14]) of M254
时间窗: Predose (baseline) up to Day 14 post dose
AUEC(0-Day 14) is defined as the area under effect curve of the change from baseline in platelet count from Day 0 to Day 14 of M254. Baseline was the predose sample. Data was planned to be collected and analyzed for Part C only. For Part C, data were collected and analyzed on the pooled population per the study drug (M254 120 mg/kg and IVIg 1000 mg/kg) which the participants received.
次要结局
- Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Volume of Distribution (Vz) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Clearance (CL) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254(Predose (baseline) up to Day 29 post dose)
- Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg(Up to Day 29)
- Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-Last]) of M254(Predose (baseline) up to Day 29 post dose)
- Parts A, B, and C: Mean Residence Time (MRT) of M254(Predose (baseline) up to Day 29 post dose)