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

NCT03866577 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: CR1089792018-003534-32MOM-M254-001
• Study Type: interventional
• Target: 50
• Locations: 7 countries
• Sites: 28

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.

Conditions

Immune Thrombocytopenic Purpura (ITP)

Keywords

Immune thrombocytopenic purpura; Healthy subjects; M254; Intravenous immunoglobulin (IVIg)

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (10)

• Part C: Number of Participants With Overall Platelet Response After M254 Administration Compared to IVIg

  Up to Day 29

• Parts A, B, and C: Maximum Observed Plasma Concentration (Cmax) of M254

  Predose (baseline) up to Day 29 post dose

• Parts A, B, and C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of M254

  Predose (baseline) up to Day 29 post dose

• Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of M254

  Predose (baseline) up to Day 29 post dose

• Parts A, B, and C: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-Last]) of M254

  Predose (baseline) up to Day 29 post dose

Study Arms (4)

Part A

EXPERIMENTAL

Healthy volunteers will receive a single ascending dose of M254 or placebo

Biological: Biological: M254; Drug: Placebo

Part B

EXPERIMENTAL

Immune thrombocytopenic purpura (ITP) patients will receive a single ascending dose of M254 followed by IVIg

Biological: Biological: M254; Biological: Intravenous immunoglobulin (IVIg)

Part C

EXPERIMENTAL

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; Biological: Intravenous immunoglobulin (IVIg)

Part D

EXPERIMENTAL

ITP patients will receive repeated doses of M254

Biological: Biological: M254

Interventions

Biological: M254 BIOLOGICAL

M254 administered as intravenous infusion

Part A; Part B; Part C; Part D

Placebo DRUG

Placebo administered as intravenous infusion

Part A

Intravenous immunoglobulin (IVIg) BIOLOGICAL

IVIg administered as intravenous infusion

Part B; Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Momenta Pharmaceuticals, Inc.: lead

Study Sites (28)

University of Southern California

Los Angeles, California, 90089, United States

Location

Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

University of South Florida

St. Petersburg, Florida, 33701, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Taussig Cancer Insititute Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ucl de Mont-Godinne

Yvoir, 5530, Belgium

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, 7400, Hungary

Location

Pecsi Tudomanyegyetem

Pécs, 7624, Hungary

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Azienda Unita Sanitaria Locale di Ravenna

Ravenna, 48100, Italy

Location

Arcispedale Santa Maria Nuova - IRCCS

Reggio Emilia, 42123, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 168, Italy

Location

Ospedale 'Casa Sollievo della Sofferenza' - U.O. Ematologia-

San Giovanni Rotondo, 71013, Italy

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

PRA Health Sciences

Groningen, NZ 9728, Netherlands

Location

Silesian Healthy Blood Clinic

Chorzów, 41 503, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1

Lublin, 20-081, Poland

Location

Szpital Wojewodzki w Opolu

Opole, 45-061, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSW w Poznaniu im prof Ludwika Bierkowskiego

Poznan, 60-631, Poland

Location

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50 367, Poland

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. Univ. de Burgos

Burgos, 09003, Spain

Location

Hosp. Regional. Carlos Haya

Málaga, 29010, Spain

Location

Hosp. Gral. Univ. J.M. Morales Meseguer

Murcia, 30008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Dr. Peset

Valencia, 46017, Spain

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Part C (Group 2) and Part D were planned but not conducted based on sponsor decision to discontinue the study after completion of Part A, Part B, and Part C (Group 1). No safety concerns were identified and study was terminated for business reasons.

Results Point of Contact

• Title: Senior Director Clinical Development Head Rheumatology
• Organization: Momenta Pharmaceuticals, Inc.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Momenta General Queries

  Momenta Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Part A: Double (Subject, Investigator); Part B, C, and D: Open Label Investigations
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: March 7, 2019
• Study Start: December 21, 2018
• Primary Completion: June 9, 2021
• Study Completion: June 9, 2021
• Last Updated: May 28, 2025
• Results First Posted: July 1, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); HU (3); PL (5); IT (5); BE (1); NL (2); ES (6)