Immune Thrombocytopenic Purpura (ITP)
Conditions
Keywords
Immune thrombocytopenic purpura, Healthy subjects, M254, Intravenous immunoglobulin (IVIg)
Brief summary
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.
Detailed description
The Part A of the study is currently not accepting healthy volunteers as the recruitment for the part A has completed.
Interventions
BIOLOGICALBiological: M254
M254 administered as intravenous infusion
DRUGPlacebo
Placebo administered as intravenous infusion
BIOLOGICALIntravenous immunoglobulin (IVIg)
IVIg administered as intravenous infusion
Sponsors
Momenta Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Part A: Double (Subject, Investigator); Part B, C, and D: Open Label Investigations
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Criteria for Healthy Volunteers: Subject must be between the ages of 18 and 55 years; healthy as indicated by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram, and all abnormal findings are assessed as not clinically significant by the Investigator; not pregnant or breastfeeding; and no other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate. Key Criteria for Immune Thrombocytopenic Purpura (ITP) Patients: Patient must be aged ≥18 years and diagnosed with ITP at least 3 months prior to screening, stable maintenance therapy for at least 4 weeks prior to the first study visit, not pregnant or breastfeeding, and no other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 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 Clinical Laboratory Values | 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 Clinically Significant Abnormalities in Vital Signs | 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) | 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 | 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 | 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 14 (AUEC[0-Day 14]) of M254 | 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. |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts A, B, and C: Mean Residence Time (MRT) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
| 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 | 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. |
| 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 | 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. |
| Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg | Up to Day 29 | 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. |
| Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
| Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
| 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 | 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. |
| Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
| Parts A, B, and C: Volume of Distribution (Vz) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
| Parts A, B, and C: Clearance (CL) of M254 | Predose (baseline) up to Day 29 post dose | 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. |
Countries
Belgium, Hungary, Italy, Netherlands, Poland, Spain, United States
Participant flow
Pre-assignment details
Part C Group 2 and Part D of the study was not conducted as planned due to early study termination.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Pooled Placebo All healthy participants of Part A received a single intravenous (IV) infusion of matching placebo on Day 1. | 7 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) Healthy participants received a single IV infusion of M254 3 mg/kg on Day 1. | 3 |
| Part A: M254 10 mg/kg Healthy participants received a single IV infusion of M254 10 mg/kg on Day 1. | 3 |
| Part A: M254 30 mg/kg Healthy participants received a single IV infusion of M254 30 mg/kg on Day 1. | 3 |
| Part A: M254 60 mg/kg Healthy participants received a single IV infusion of M254 60 mg/kg on Day 1. | 3 |
| Part A: M254 120 mg/kg Healthy participants received a single IV infusion of M254 120 mg/kg on Day 1. | 3 |
| Part A: M254 250 mg/kg Healthy participants received a single IV infusion of M254 250 mg/kg on Day 1. | 3 |
| Part B: M254 20 mg/kg and IV Immunoglobulin (IVIg) 1000 mg/kg Participants with immune thrombocytopenia purpura (ITP) received a single IV infusion of M254 20 mg/kg on Day 1 followed by a single IV infusion of IVIg 1000 mg/kg on Day 29. | 2 |
| Part B: M254 60 mg/kg and IVIg 1000 mg/kg Participants with ITP received a single IV infusion of M254 60 mg/kg on Day 1 followed by a single IV infusion of IVIg 1000 mg/kg on Day 29. | 5 |
| Part B: M254 120 mg/kg and IVIg 1000 mg/kg Participants with ITP received a single IV infusion of M254 120 mg/kg on Day 1 followed by a single IV infusion of IVIg 1000 mg/kg on Day 29. | 5 |
| Part B: M254 250 mg/kg and IVIg 1000 mg/kg Participants with ITP received a single IV infusion of M254 250 mg/kg on Day 1 followed by a single IV infusion of IVIg 1000 mg/kg on Day 29. | 2 |
| Part C (Group 1): M254 120 mg/kg and IVIg 1000 mg/kg Participants with ITP received a single IV infusion of M254 120 mg/kg on Day 1 followed by a single IV infusion of IVIg 1000 mg/kg on Day 29. | 6 |
| Part C (Group 1): IVIg 1000 mg/kg and M254 120 mg/kg Participants with ITP received a single IV infusion of IVIg 1000 mg/kg on Day 1 followed by a single IV infusion of M254 120 mg/kg on Day 29. | 5 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Not qualified for IVIg infusion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Pooled Placebo | Part A: M254 3 Milligrams/Kilogram (mg/kg) | Part A: M254 10 mg/kg | Part A: M254 30 mg/kg | Part A: M254 60 mg/kg | Part A: M254 120 mg/kg | Part A: M254 250 mg/kg | Part B: M254 20 mg/kg and IV Immunoglobulin (IVIg) 1000 mg/kg | Part B: M254 60 mg/kg and IVIg 1000 mg/kg | Part B: M254 120 mg/kg and IVIg 1000 mg/kg | Part B: M254 250 mg/kg and IVIg 1000 mg/kg | Part C (Group 1): M254 120 mg/kg and IVIg 1000 mg/kg | Part C (Group 1): IVIg 1000 mg/kg and M254 120 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.9 years STANDARD_DEVIATION 10.9 | 31.3 years STANDARD_DEVIATION 7.64 | 32 years STANDARD_DEVIATION 13.75 | 27 years STANDARD_DEVIATION 1 | 29 years STANDARD_DEVIATION 7.81 | 32.7 years STANDARD_DEVIATION 15.53 | 24.3 years STANDARD_DEVIATION 4.51 | 44 years STANDARD_DEVIATION 4.24 | 51.8 years STANDARD_DEVIATION 11.45 | 44 years STANDARD_DEVIATION 12.94 | 54.5 years STANDARD_DEVIATION 13.44 | 58 years STANDARD_DEVIATION 14.48 | 60 years STANDARD_DEVIATION 12.63 | 41.7 years STANDARD_DEVIATION 15.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 5 Participants | 2 Participants | 6 Participants | 5 Participants | 45 Participants |
| Region of Enrollment Belgium | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Hungary | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Italy | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Netherlands | 7 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 27 Participants |
| Region of Enrollment Poland | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 15 Participants |
| Region of Enrollment Spain | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 26 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 6 / 7 | 3 / 3 | 3 / 3 | 3 / 3 | 0 / 3 | 3 / 3 | 3 / 3 | 1 / 2 | 0 / 2 | 2 / 5 | 2 / 4 | 1 / 5 | 1 / 3 | 0 / 2 | 0 / 2 | 1 / 6 | 0 / 5 | 2 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 3 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
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
Population: The full analysis set consisted of all participants who received at least 1 dose of M254 or IVIg or placebo and for whom at least 1 post-infusion PD assessment was completed. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | 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 | 3938 10^9 cells *hours per liter | Standard Deviation 3952 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | 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 | 21199 10^9 cells *hours per liter | Standard Deviation 19349 |
Primary
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
Population: The full analysis set consisted of all participants who received at least 1 dose of M254 or IVIg or placebo and for whom at least 1 post-infusion PD assessment was completed. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | 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 | 5774 10^9 cells *hours per liter | Standard Deviation 9453 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | 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 | 29985 10^9 cells *hours per liter | Standard Deviation 29265 |
Primary
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
Population: The full analysis set consisted of all participants who received at least 1 dose of M254 or IVIg or placebo and for whom at least 1 post-infusion PD assessment was completed. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change From Baseline in Rmax of M254 in Platelet Count | 28.8 10^9 cells per liter | Standard Deviation 22.2 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Part C: Change From Baseline in Rmax of M254 in Platelet Count | 10.5 10^9 cells per liter | Standard Deviation 67.3 |
Primary
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
Population: The full analysis set consisted of all participants who received at least 1 dose of M254 or IVIg or placebo and for whom at least 1 post-infusion pharmacodynamics (PD) assessment was completed. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Maximum Observed Response of M254 (Rmax) on Platelet Count | 62.4 10^9 cells per liter | Standard Deviation 20.1 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Part C: Maximum Observed Response of M254 (Rmax) on Platelet Count | 136 10^9 cells per liter | Standard Deviation 70 |
Primary
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
Population: Safety analysis set included all participants who received at least 1 dose of M254 or IVIg or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 10 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 30 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 60 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 120 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part A: M254 250 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| Part B: M254 120 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 1 Participants |
Primary
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.
Time frame: From Day 1 up to Day 29
Population: Safety analysis set included all participants who received at least 1 dose of M254 or IVIg or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 10 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 30 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 60 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 120 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part A: M254 250 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
| Part B: M254 120 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Electrocardiograms (ECGs) | 0 Participants |
Primary
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
Population: Safety analysis set included all participants who received at least 1 dose of M254 or IVIg or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 10 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 30 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 60 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 120 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part A: M254 250 mg/kg | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 1 Participants |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Part B: M254 120 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Clinically Significant Abnormalities in Vital Signs | 1 Participants |
Primary
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
Population: Safety analysis set included all participants who received at least 1 dose of M254 or IVIg or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 6 Participants |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 3 Participants |
| Part A: M254 10 mg/kg | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 3 Participants |
| Part A: M254 30 mg/kg | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 3 Participants |
| Part A: M254 60 mg/kg | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 0 Participants |
| Part A: M254 120 mg/kg | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 3 Participants |
| Part A: M254 250 mg/kg | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 3 Participants |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 1 Participants |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 0 Participants |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 2 Participants |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 2 Participants |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 1 Participants |
| Part B: M254 120 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 1 Participants |
| Part B: M254 250 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 0 Participants |
| Part B: M254 250 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 0 Participants |
| Part C (Group 1) : M254 120 mg/kg and IVIg 1000 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 1 Participants |
| Part C (Group 1): M254 120 mg/kg and IVIg 1000 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 0 Participants |
| Part C (Group 1): IVIg 1000 mg/kg and M254 120 mg/kg - IVIg Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 2 Participants |
| Part C (Group 1): IVIg 1000 mg/kg and M254 120 mg/kg - M254 Period | Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity | 2 Participants |
Secondary
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
Population: The full analysis set consisted of all participants who were included in the safety set for whom at least 1 post-infusion PD assessment was completed. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg | 8 Participants |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg | 9 Participants |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | NA hours |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 466 hours |
| Part A: M254 10 mg/kg | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 463 hours |
| Part A: M254 30 mg/kg | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 517 hours |
| Part A: M254 60 mg/kg | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 609 hours |
| Part A: M254 120 mg/kg | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 659 hours |
| Part A: M254 250 mg/kg | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 548 hours |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 387 hours |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 478 hours |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 437 hours |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 467 hours |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Apparent Terminal Phase Half-life (t1/2) of M254 | 391 hours |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | NA micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 21488 micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 10 mg/kg | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 72050 micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 30 mg/kg | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 210916 micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 60 mg/kg | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 645641 micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 120 mg/kg | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 1178098 micrograms*hour milliliter (mcg*h/mL) |
| Part A: M254 250 mg/kg | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 2196380 micrograms*hour milliliter (mcg*h/mL) |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 132265 micrograms*hour milliliter (mcg*h/mL) |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 423957 micrograms*hour milliliter (mcg*h/mL) |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 928888 micrograms*hour milliliter (mcg*h/mL) |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 1839253 micrograms*hour milliliter (mcg*h/mL) |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254 | 1112165 micrograms*hour milliliter (mcg*h/mL) |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | 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 | 593 mcg*h/mL |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | 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 | 11531 mcg*h/mL |
| Part A: M254 10 mg/kg | 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 | 39509 mcg*h/mL |
| Part A: M254 30 mg/kg | 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 | 111564 mcg*h/mL |
| Part A: M254 60 mg/kg | 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 | 272532 mcg*h/mL |
| Part A: M254 120 mg/kg | 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 | 652747 mcg*h/mL |
| Part A: M254 250 mg/kg | 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 | 1294774 mcg*h/mL |
| Part B: M254 20 mg/kg - M254 Period | 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 | 96329 mcg*h/mL |
| Part B: M254 20 mg/kg - IVIg Period | 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 | 287567 mcg*h/mL |
| Part B: M254 60 mg/kg - M254 Period | 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 | 588913 mcg*h/mL |
| Part B: M254 60 mg/kg - IVIg Period | 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 | 1182466 mcg*h/mL |
| Part B: M254 120 mg/kg - M254 Period | 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 | 700805 mcg*h/mL |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Clearance (CL) of M254 | 9.63 milliliters per hour (mL/h) |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Clearance (CL) of M254 | 9.85 milliliters per hour (mL/h) |
| Part A: M254 10 mg/kg | Parts A, B, and C: Clearance (CL) of M254 | 7.62 milliliters per hour (mL/h) |
| Part A: M254 30 mg/kg | Parts A, B, and C: Clearance (CL) of M254 | 7.59 milliliters per hour (mL/h) |
| Part A: M254 60 mg/kg | Parts A, B, and C: Clearance (CL) of M254 | 6.79 milliliters per hour (mL/h) |
| Part A: M254 120 mg/kg | Parts A, B, and C: Clearance (CL) of M254 | 7.69 milliliters per hour (mL/h) |
| Part A: M254 250 mg/kg | Parts A, B, and C: Clearance (CL) of M254 | 15.6 milliliters per hour (mL/h) |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Clearance (CL) of M254 | 12.0 milliliters per hour (mL/h) |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Clearance (CL) of M254 | 9.69 milliliters per hour (mL/h) |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Clearance (CL) of M254 | 14.3 milliliters per hour (mL/h) |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Clearance (CL) of M254 | 10.1 milliliters per hour (mL/h) |
Secondary
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
Population: Pharmacokinetic (PK) data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 3.20 micrograms per milliliter (mcg/mL) |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 53.9 micrograms per milliliter (mcg/mL) |
| Part A: M254 10 mg/kg | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 174 micrograms per milliliter (mcg/mL) |
| Part A: M254 30 mg/kg | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 575 micrograms per milliliter (mcg/mL) |
| Part A: M254 60 mg/kg | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 1240 micrograms per milliliter (mcg/mL) |
| Part A: M254 120 mg/kg | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 2684 micrograms per milliliter (mcg/mL) |
| Part A: M254 250 mg/kg | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 5444 micrograms per milliliter (mcg/mL) |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 431 micrograms per milliliter (mcg/mL) |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 1338 micrograms per milliliter (mcg/mL) |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 2650 micrograms per milliliter (mcg/mL) |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 5624 micrograms per milliliter (mcg/mL) |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254 | 3068 micrograms per milliliter (mcg/mL) |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 570 hours | Standard Deviation 190 |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 654 hours | Standard Deviation 75.9 |
| Part A: M254 10 mg/kg | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 676 hours | Standard Deviation 107 |
| Part A: M254 30 mg/kg | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 867 hours | Standard Deviation 79.8 |
| Part A: M254 60 mg/kg | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 820 hours | Standard Deviation 163 |
| Part A: M254 120 mg/kg | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 818 hours | Standard Deviation 189 |
| Part A: M254 250 mg/kg | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 517 hours | — |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 661 hours | Standard Deviation 77 |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 653 hours | Standard Deviation 109 |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 610 hours | — |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Mean Residence Time (MRT) of M254 | 584 hours | Standard Deviation 177 |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, N (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 46.3 Percentage of AUC(0-infinity) |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 45.1 Percentage of AUC(0-infinity) |
| Part A: M254 10 mg/kg | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 49.8 Percentage of AUC(0-infinity) |
| Part A: M254 30 mg/kg | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 51.9 Percentage of AUC(0-infinity) |
| Part A: M254 60 mg/kg | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 46.5 Percentage of AUC(0-infinity) |
| Part A: M254 120 mg/kg | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 40.1 Percentage of AUC(0-infinity) |
| Part A: M254 250 mg/kg | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 27.2 Percentage of AUC(0-infinity) |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 37.0 Percentage of AUC(0-infinity) |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 31.9 Percentage of AUC(0-infinity) |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 33.2 Percentage of AUC(0-infinity) |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Percentage of the Estimated Part for the Calculation of AUC(0-infinity) (%AUCextra) of M254 | 27.6 Percentage of AUC(0-infinity) |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 338.68 hours |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 0.60 hours |
| Part A: M254 10 mg/kg | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 0.45 hours |
| Part A: M254 30 mg/kg | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 0.77 hours |
| Part A: M254 60 mg/kg | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.23 hours |
| Part A: M254 120 mg/kg | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.83 hours |
| Part A: M254 250 mg/kg | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 2.62 hours |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.02 hours |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.48 hours |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.93 hours |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 2.74 hours |
| Part B: M254 120 mg/kg - M254 Period | Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254 | 1.85 hours |
Secondary
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
Population: PK data analysis set included all randomized participants who received at least 1 dose of M254 or IVIg or placebo with at least 4 evaluable data points adequate to create an evaluable plasma concentration profile of M254. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 6481 milliliter (mL) |
| Part A: M254 3 Milligrams/Kilogram (mg/kg) | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 6129 milliliter (mL) |
| Part A: M254 10 mg/kg | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 5447 milliliter (mL) |
| Part A: M254 30 mg/kg | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 7105 milliliter (mL) |
| Part A: M254 60 mg/kg | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 6383 milliliter (mL) |
| Part A: M254 120 mg/kg | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 6419 milliliter (mL) |
| Part A: M254 250 mg/kg | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 8679 milliliter (mL) |
| Part B: M254 20 mg/kg - M254 Period | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 5259 milliliter (mL) |
| Part B: M254 20 mg/kg - IVIg Period | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 7258 milliliter (mL) |
| Part B: M254 60 mg/kg - M254 Period | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 9623 milliliter (mL) |
| Part B: M254 60 mg/kg - IVIg Period | Parts A, B, and C: Volume of Distribution (Vz) of M254 | 6059 milliliter (mL) |