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.
The Part A of the study is currently not accepting healthy volunteers as the recruitment for the part A has completed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
M254 administered as intravenous infusion
Placebo administered as intravenous infusion
IVIg administered as intravenous infusion
Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
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.
Time frame: From Day 1 up to Day 29
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values
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.
Time frame: From Day 1 up to Day 29
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs
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.
Time frame: From Day 1 up to Day 29
Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs)
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.
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University of Southern California
Los Angeles, California, United States
Oncology Institute of Hope and Innovation
Whittier, California, United States
Lakes Research
Miami Lakes, Florida, United States
University of South Florida
St. Petersburg, Florida, United States
Duke University Medical Center
Durham, North Carolina, United States
Taussig Cancer Insititute Cleveland Clinic
Cleveland, Ohio, United States
Ucl de Mont-Godinne
Yvoir, Belgium
Debreceni Egyetem Klinikai Kozpont
Debrecen, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, Hungary
Pecsi Tudomanyegyetem
Pécs, Hungary
...and 18 more locations
Time frame: From Day 1 up to Day 29
Part C: Maximum Observed Response of M254 (Rmax) on Platelet Count
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.
Time frame: Predose (baseline) up to Day 29 post dose
Part C: Change From Baseline in Rmax of M254 in Platelet Count
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.
Time frame: Predose (baseline) up to Day 29 post dose
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
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.
Time frame: Predose (baseline) up to Day 14 post dose
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
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.
Time frame: Predose (baseline) up to Day 29 post dose
Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg
Number of participants with overall platelet response after M254 administration compared to IVIg were reported. Overall platelet response rate is defined as reaching the therapeutic platelet count. A therapeutic platelet count is defined as greater than or equal to (\>=) 50\*10\^9 cells/liter (L) and an increase from baseline of \>=20\*10\^9 cells/L. 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.
Time frame: Up to Day 29
Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254
Cmax is defined as the maximum observed plasma concentration of M254. Baseline was the predose sample. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose
Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254
Tmax is defined as the time to reach the maximum observed plasma concentration of M254. Baseline was the predose sample. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: 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
AUC(0-Infinity) is defined as area under the plasma concentration-time curve from time 0 to infinite time of M254. Baseline was the predose sample. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: 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
AUC(0-last) is defined as area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration of M254. AUC(0-last) is calculated by linear-linear trapezoidal summation. Baseline was the predose sample. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose
Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254
t1/2 is defined as the time measured for the plasma concentration to decrease by 1 half to its original concentration of M254. Baseline was the predose sample. Data was planned to be collected and analyzed on pooled population of participants who received placebo in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose
Parts A, B, and C: Volume of Distribution (Vz) of M254
Vz is defined as volume of distribution of M254 at terminal phase. Baseline was the predose sample. Data for this outcome measure was not planned for pooled placebo arm in Part A and thus no data was presented for placebo arm in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose
Parts A, B, and C: Clearance (CL) of M254
CL is defined as clearance of M254, calculated as dose/AUC(0-infinity). Baseline was the predose sample. Data for this outcome measure was not planned for pooled placebo arm in Part A and thus no data was presented for placebo arm in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose
Parts A, B, and C: Mean Residence Time (MRT) of M254
Mean residence time is the average time that drug dose remained in the body. Baseline was the predose sample. Data for this outcome measure was not planned for pooled placebo arm in Part A and thus no data was presented for placebo arm in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: 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
Percentage of the estimated part for the calculation of AUC(0-infinity) (%AUCextra) of M254 were reported. Baseline was the predose sample. Data for this outcome measure was not planned for pooled placebo arm in Part A and thus no data was presented for placebo arm in Part A. In Part C, combined data of both arms of Group 1 is presented as planned.
Time frame: Predose (baseline) up to Day 29 post dose