Study of MGTA-145 and Plerixafor in Patients With Sickle Cell Disease

Study Overview
=================
Brief Summary
-----------------
This research study is designed to investigate a new potential medicine for mobilizing stem cells and apheresis collection in patients with Sickle Cell Disease. MGTA-145, the new potential medicine, will be given with plerixafor.

Detailed Description
-----------------
This Phase 2, multicenter, open-label study will be conducted in 2 parts (Parts A and B). Part A is intended to characterize the efficacy, safety, PK and PD of a single dose of MGTA-145 and plerixafor for HSC mobilization and apheresis collection in patients with SCD. Part B is designed to characterize the efficacy, safety, PK and PD of 2 consecutive days of dosing with MGTA-145 and plerixafor for HSC mobilization and apheresis collection in patients with SCD.

Official Title
-----------------
A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of MGTA-145 in Combination With Plerixafor for the Mobilization of Hematopoietic Stem Cells in Patients With Sickle Cell Disease

Conditions
-----------------
Sickle Cell Disease

Intervention / Treatment
-----------------
* Biological: MGTA-145
* Drug: Plerixafor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must be ≥18 to ≤35 years of age. Subject must weigh ≥30 kg. Subject must have a diagnosis of Sickle Cell Disease. Exclusion Criteria: Subject must not have had a vaso-occlusive event (VOE) requiring a visit to a healthcare facility within 30 days of screening. Subject must not have undergone or attempted and failed previous hematopoietic stem cell (HSC) collection. Subject must not have had a prior autologous or allogeneic transplantation, inclusive of gene therapy. Male subject must be willing or able to use a highly effective method of contraception for 3 months during and after treatment. Female subject must not be pregnant or breastfeeding. If sexually active, female subject must be willing or able to use a highly effective method of contraception for 3 months during and after treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Day Dosing/Apheresis<br>Single dose of MGTA-145 in combination with plerixafor followed by apheresis | Biological: MGTA-145<br>* MGTA-145 will be administered as an IV infusion<br>Drug: Plerixafor<br>* 240 µg/kg administered subcutaneously<br>|
| Experimental: Part B: 2-Day Dosing/Apheresis<br>MGTA-145 in combination with plerixafor followed by apheresis on two consecutive days | Biological: MGTA-145<br>* MGTA-145 will be administered as an IV infusion<br>Drug: Plerixafor<br>* 240 µg/kg administered subcutaneously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apheresis Collection Yield | Determination of the yield of CD34+ cells after either one or two consecutive days of MGTA-145 and plerixafor mobilization followed by apheresis. | Up to 2 days | 
| Assess incidence of treatment emergent adverse events leading to study drug discontinuation based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |  | Up to 30 days | 
| Assess the incidence of treatment emergent >/= Grade 3 clinical laboratory abnormalities based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |  | Up to 11 days | 
| Vital Signs - Number of participants with clinically significant changes from baseline in vital signs |  | Up to 11 days | 
| Laboratory Assessment - Number of participants with clinically significant changes from baseline in hematology and clinical chemistry laboratory parameters. |  | Up to 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mobilization Effects of single-day and two-day dosing with MGTA-145 and plerixafor in peripheral blood in patients with SCD | Determination of peak peripheral blood CD34+ counts | Up to 2 days | 
| Investigate plasma concentrations of MGTA-145 per timepoint of collection (Pharmacokinetics) |  | Up to 2 days | 
| Assess presence of MGTA-145 Anti-Drug Antibodies (ADA) in plasma samples (using electrochemiluminescent immunoassay [ECLIA]) |  | Up to 11 days | 
| Assess titers of MGTA-145 Anti-Drug Antibodies (ADA) in plasma samples (using electrochemiluminescent immunoassay [ECLIA]) |  | Up to 11 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SCD, MGTA-145, Plerixafor, Mobilization, Apheresis