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

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

Official Title
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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

Conditions
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Immune Thrombocytopenic Purpura (ITP)

Intervention / Treatment
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* Biological: Biological: M254
* Drug: Placebo
* Biological: Intravenous immunoglobulin (IVIg)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Severity of Adverse Events (AEs) - Part A |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Clinical Safety Laboratory Values - Part A |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Clinical Safety Laboratory Values - Part A |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Vital Signs - Part A |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Vital Signs - Part A |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Electrocardiograms (ECGs) - Part A |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Electrocardiograms (ECGs) - Part A |  | Up to approximately Day 29 | 
| Number and Severity of AEs - Part B |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Clinical Safety Laboratory Values - Part B |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Clinical Safety Laboratory Values - Part B |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Vital Signs - Part B |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Vital Signs - Part B |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in ECGs - Part B |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for ECGs - Part B |  | Up to approximately Day 29 | 
| Number and Severity of AEs - Part C |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Clinical Safety Laboratory Values - Part C |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Clinical Safety Laboratory Values - Part C |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in Vital Signs - Part C |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for Vital Signs - Part C |  | Up to approximately Day 29 | 
| Frequency of Clinically Significant Abnormalities in ECGs - Part C |  | Up to approximately Day 29 | 
| Shift From Baseline in Clinically Significant Abnormalities for ECGs - Part C |  | Up to approximately Day 29 | 
| Measurement of Changes in Platelet Counts After M254 Administration Compared to IVIg - Part C |  | Baseline to approximately Day 29 | 
| Number and Severity of AEs - Part D |  | Up to approximately Day 71 | 
| Frequency of Clinically Significant Abnormalities in Clinical Safety Laboratory Values - Part D |  | Up to approximately Day 71 | 
| Shift From Baseline in Clinically Significant Abnormalities for Clinical Safety Laboratory Values - Part D |  | Up to approximately Day 71 | 
| Frequency of Clinically Significant Abnormalities in Vital Signs - Part D |  | Up to approximately Day 71 | 
| Shift From Baseline in Clinically Significant Abnormalities for Vital Signs - Part D |  | Up to approximately Day 71 | 
| Frequency of Clinically Significant Abnormalities in ECGs - Part D |  | Up to approximately Day 71 | 
| Shift From Baseline in Clinically Significant Abnormalities for ECGs - Part D |  | Up to approximately Day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Time to Maximum Plasma Concentration (Tmax) of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Area Under the Concentration-time Curve From Zero to Time of Last Measurable Concentration Area [AUC(0 last)] of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Area Under the Concentration-time Curve From Zero to Infinity [AUC(0 ∞)] of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Volume of Distribution (Vd) of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Clearance of Drug (CL) M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Mean Residence Time (MRT) of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Apparent Terminal-phase Half-life (t½) of M254 - Part A, B, and C |  | Day 1 to Day 29 | 
| Cmax of M254 - Part D |  | Day 1 to Day 71 | 
| Tmax of M254 - Part D |  | Day 1 to Day 71 | 
| AUC(0 last) of M254 - Part D |  | Day 1 to Day 71 | 
| AUC(0 ∞) of M254 - Part D |  | Day 1 to Day 71 | 
| Vd of M254 - Part D |  | Day 1 to Day 71 | 
| CL of M254 - Part D |  | Day 1 to Day 71 | 
| MRT of M254 - Part D |  | Day 1 to Day 71 | 
| t½ of M254 - Part D |  | Day 1 to Day 71 | 
| Measurements of Changes in Platelet Counts After M254 Administration - Part D |  | Baseline to approximately Day 71 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune thrombocytopenic purpura, Healthy subjects, M254, Intravenous immunoglobulin (IVIg)