Safety and Tolerability of M254 in Healthy Volunteers and Immune Thrombocytopenic Purpura (ITP) Patients

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

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.

Study Overview

• Status: Terminated
• Conditions: Immune Thrombocytopenic Purpura (ITP)
• Intervention / Treatment: Drug: Placebo; Biological: Biological: M254; Biological: Intravenous immunoglobulin (IVIg)

Detailed Description

The Part A of the study is currently not accepting healthy volunteers as the recruitment for the part A has completed.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Yvoir, Belgium, 5530
    • Ucl de Mont-Godinne
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Kaposvar, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Pecs, Hungary, 7624
    • Pécsi Tudományegyetem
• Italy
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Ravenna, Italy, 48100
    • Azienda Unita Sanitaria Locale Di Ravenna
  • Reggio Emilia, Italy, 42123
    • Arcispedale Santa Maria Nuova - IRCCS
  • Roma, Italy, 168
    • Policlinico Universitario Agostino Gemelli
  • San Giovanni Rotondo, Italy, 71013
    • Ospedale 'Casa Sollievo della Sofferenza' - U.O. Ematologia-
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Groningen, Netherlands, NZ 9728
    • PRA Health Sciences
• Poland
  • Chorzow, Poland, 41 503
    • Silesian Healthy Blood Clinic
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1
  • Opole, Poland, 45-061
    • Szpital Wojewodzki w Opolu
  • Poznan, Poland, 60-631
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSW w Poznaniu im prof Ludwika Bierkowskiego
  • Wroclaw, Poland, 50 367
    • Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
• Spain
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Burgos, Spain, 09003
    • Hosp. Univ. de Burgos
  • Malaga, Spain, 29010
    • Hosp. Regional. Carlos Haya
  • Murcia, Spain, 30008
    • Hosp. Gral. Univ. J.M. Morales Meseguer
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
  • Valencia, Spain, 46017
    • Hosp. Univ. Dr. Peset
• United States
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California
    • Whittier, California, United States, 90603
      • Oncology Institute of Hope and Innovation
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
    • Saint Petersburg, Florida, United States, 33701
      • University of South Florida
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Taussig Cancer Insititute Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Healthy volunteers will receive a single ascending dose of M254 or placebo	Drug: Placebo; Placebo administered as intravenous infusion; Biological: Biological: M254; M254 administered as intravenous infusion
Experimental: Part B; Immune thrombocytopenic purpura (ITP) patients will receive a single ascending dose of M254 followed by IVIg	Biological: Biological: M254; M254 administered as intravenous infusion; Biological: Intravenous immunoglobulin (IVIg); IVIg administered as intravenous infusion
Experimental: 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	Biological: Biological: M254; M254 administered as intravenous infusion; Biological: Intravenous immunoglobulin (IVIg); IVIg administered as intravenous infusion
Experimental: Part D; ITP patients will receive repeated doses of M254	Biological: Biological: M254; M254 administered as intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	Predose (baseline) up to Day 29 post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Predose (baseline) up to Day 29 post dose

Collaborators and Investigators

• Sponsor: Momenta Pharmaceuticals, Inc.
• Investigators: Study Director: Momenta General Queries, Momenta Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): June 9, 2021
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: February 12, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Healthy subjects; Immune thrombocytopenic purpura; M254; Intravenous immunoglobulin (IVIg)
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Thrombocytopenia; Purpura; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombocytopenic; Immunologic Factors; Physiological Effects of Drugs; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: CR108979; 2018-003534-32 (EudraCT Number); MOM-M254-001 (Other Identifier: Momenta Pharmaceuticals, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No