Study Assessing Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MGTA-145 in Healthy Volunteers as a Single Agent or in Combination With Plerixafor

Study Overview
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Brief Summary
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To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of MGTA-145 in healthy volunteers as a single agent and in combination with plerixafor.

Detailed Description
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The study consists of up to four parts: Part A, to investigate the safety and tolerability of MGTA-145; Part B, to investigate the safety and tolerability of MGTA-145 when administered in combination with plerixafor; Part C, to investigate the safety and tolerability of two sequential days of dosing MGTA-145 in combination with plerixafor; and Part D, to investigate the safety, tolerability, and measure by apheresis, the total number of CD34+ cells mobilized after a dose of MGTA-145 administered in combination with plerixafor.

Official Title
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A Randomized, Placebo-Controlled, Ascending Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Parameters of MGTA-145 in Healthy Subjects Administered as a Single Agent, as Well as in Combination With Plerixafor

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: MGTA-145
* Biological: plerixafor
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 60 years Body weight ≥50 kg and body mass index 19 to 33 kg/m2 No clinically significant abnormalities on physical examination at Screening Non-smoker for at least 2 years No clinically significant lab abnormalities for renal, hepatic or hematologic parameters No clinically significant abnormalities on ECG Female subjects must be of non-childbearing potential Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception No contraindications for apheresis Exclusion Criteria: Any clinically significant laboratory value outside the normal range at screening Donation of more than 500 mL of blood or plasma within 12 weeks prior to dosing History of alcoholism or drug abuse within the past 3 years Subject has used any prescription drugs within 14 days prior to dosing or any dietary supplements or non-prescription drugs within 7 days prior to dosing Acute illness, infection (requiring medical treatment [eg, antibiotics]), or surgery within 4 weeks of dosing Seropositive for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus Subject has received another investigational drug or participated in an investigational drug or device study within 12 weeks prior to dosing History of anaphylaxis or clinically important reaction to any drug including plerixafor Any clinically significant hematologic, cardiovascular, pulmonary, central nervous system, metabolic, renal, hepatic, or gastrointestinal conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Single Ascending Dose of MGTA-145 or placebo<br>MGTA-145 or placebo dose escalation as single agent, single dose | Biological: MGTA-145<br>* MGTA-145 will be given in various doses intravenously<br>Biological: Placebo<br>* Placebo will be given in various doses intravenously<br>|
| Placebo Comparator: Single Dose MGTA-145 or placebo plus plerixafor<br>MGTA-145 or placebo in combination with plerixafor, single dose | Biological: MGTA-145<br>* MGTA-145 will be given in various doses intravenously<br>Biological: plerixafor<br>* 240 µg/kg subcutaneously<br>* Other names: Mozobil;Biological: Placebo<br>* Placebo will be given in various doses intravenously<br>|
| Experimental: Single dose MGTA-145 plus plerixafor for 2 sequential d<br>MGTA-145 in combination with plerixafor on two consecutive days; single dose per day | Biological: MGTA-145<br>* MGTA-145 will be given in various doses intravenously<br>Biological: plerixafor<br>* 240 µg/kg subcutaneously<br>* Other names: Mozobil;|
| Experimental: Single dose MGTA-145 plus plerixafor followed by apheresis<br>MGTA-145 in combination with plerixafor followed by apheresis | Biological: MGTA-145<br>* MGTA-145 will be given in various doses intravenously<br>Biological: plerixafor<br>* 240 µg/kg subcutaneously<br>* Other names: Mozobil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs). | Investigate the safety and tolerability of MGTA-145 following intravenous (IV) administration as monotherapy or in combination with plerixafor in healthy subjects (e.g. adverse events, clinical laboratory tests, vital signs, ECGs) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Biomarkers | Investigate area under the curve (AUC) of MGTA-145 | 15 days | 
| Pharmacokinetics Biomarkers | Investigate maximum plasma concentration (Cmax) of MGTA-145 | 15 days | 
| Pharmacokinetic Biomarkers | Investigate clearance (CL) of MGTA-145 | 15 days | 
| Pharmacokinetic Biomarkers | Investigate the volume of distribution at steady state (Vdss) of MGTA-145 | 15 days | 
| Pharmacokinetic Biomarkers | Investigate the half-life of MGTA-145 | 15 days | 
| Pharmacodynamic Biomarkers | Assess CD34+ cells per uL of blood by flow cytometry | 15 days | 
| Pharmacodynamic Biomarkers | Assess stem cell progenitors (colony forming units) | 15 days |