Safety and Tolerability of M254 in Healthy Volunteers and Immune Thrombocytopenic Purpura (ITP) Patients
- Conditions
- Immune Thrombocytopenic Purpura (ITP)
- Interventions
- Drug: PlaceboBiological: Intravenous immunoglobulin (IVIg)
- Registration Number
- NCT03866577
- Lead Sponsor
- Momenta Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A Placebo Healthy volunteers will receive a single ascending dose of M254 or placebo Part B Intravenous immunoglobulin (IVIg) Immune thrombocytopenic purpura (ITP) patients will receive a single ascending dose of M254 followed by IVIg Part C Intravenous immunoglobulin (IVIg) ITP patients will receive a single dose of M254 or IVIg, followed by a single dose of the other drug approximately 28 days later
- Primary Outcome Measures
Name Time Method 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 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 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 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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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: 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: 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 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: 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: 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.
Trial Locations
- Locations (28)
Samodzielny Publiczny Szpital Kliniczny Nr 1
🇵🇱Lublin, Poland
University of Southern California
🇺🇸Los Angeles, California, United States
Ucl de Mont-Godinne
🇧🇪Yvoir, Belgium
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Azienda Unita Sanitaria Locale di Ravenna
🇮🇹Ravenna, Italy
Somogy Megyei Kaposi Mor Oktato Korhaz
ðŸ‡ðŸ‡ºKaposvar, Hungary
Hosp. Regional. Carlos Haya
🇪🇸Malaga, Spain
Hosp. Univ. Dr. Peset
🇪🇸Valencia, Spain
Hosp. Univ. de Burgos
🇪🇸Burgos, Spain
Lakes Research
🇺🇸Miami Lakes, Florida, United States
University of South Florida
🇺🇸Saint Petersburg, Florida, United States
Taussig Cancer Insititute - Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Debreceni Egyetem Klinikai Kozpont
ðŸ‡ðŸ‡ºDebrecen, Hungary
Pecsi Tudomanyegyetem
ðŸ‡ðŸ‡ºPecs, Hungary
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
Arcispedale Santa Maria Nuova - IRCCS
🇮🇹Reggio Emilia, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Ospedale 'Casa Sollievo della Sofferenza' - U.O. Ematologia-
🇮🇹San Giovanni Rotondo, Italy
PRA Health Sciences
🇳🇱Groningen, Netherlands
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Szpital Wojewodzki w Opolu
🇵🇱Opole, Poland
Hosp. Univ. Vall D Hebron
🇪🇸Barcelona, Spain
Hosp. Clinico Univ. de Salamanca
🇪🇸Salamanca, Spain
Hosp. Gral. Univ. J.M. Morales Meseguer
🇪🇸Murcia, Spain
Silesian Healthy Blood Clinic
🇵🇱Chorzow, Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW w Poznaniu im. prof. Ludwika Bierkowskiego
🇵🇱Poznan, Poland