Clinical trial NCT05445128
Conditions: Sickle Cell Disease
Keywords: SCD MGTA-145 Plerixafor Mobilization Apheresis
Sponsor: Ensoma
Start date: 2022-06-24; Completion date: 2023-02-02
Enrollment: 1 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

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.

Arms: arm 1: Single dose of MGTA-145 in combination with plerixafor followed by apheresis arm 2: MGTA-145 in combination with plerixafor followed by apheresis on two consecutive days
Interventions: intervention 1: MGTA-145 intervention 2: Plerixafor
Intervention descriptions: intervention 1: MGTA-145 will be administered as an IV infusion intervention 2: 240 µg/kg administered subcutaneously

Protocol documents:
Prot_000.pdf: 
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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 
 
Investigational Product: MGTA-145 
Protocol Number: 145-SCD-204 
IND Number: 139251 
Development Phase: 2 
 
Sponsor: 
Magenta Therapeutics, Incorporated 
100 Technology Square, 5th Floor 
Cambridge, MA 02139 
 
Protocol Amendment 1, Version 3.0: 05 October 2021 
 
 
 
 
The information in this document is confidential and is not to be disclosed without the written 
consent of Magenta Therapeutics, Incorporated (Magenta), except to the extent that disclosure 
would be required by law and for the purpose of evaluating and/or conducting a clinical study for 
Magenta. Persons to whom the information is disclosed must be informed that the information is 
confidential and proprietary to Magenta and that it may not be further disclosed to third parties. 


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SIGNATURE PAGE 
STUDY 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 
I, the undersigned, have read this protocol and agree that it contains all necessary information 
required to conduct the study. 
 
 
Electronically signed by: 
Doug Girgenti 
Reason: I have approved 
this document 
Date: Oct 8, 2021 09:28 
EDT 
08-Oct-2021 
 
Douglas Girgenti, MD 
Senior Medical Director 
Magenta Therapeutics, Inc. 
Date 


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INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator’s Brochure (IB) for MGTA-145. I have read the 
145-SCD-204 protocol and agree to conduct the study as outlined. I agree to maintain the 
confidentiality of all information received or developed in connection with this protocol. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite Guidelines 
on Good Clinical Practice (GCP), effective in the United States (US) from 09 May 1997, and 
applicable US Food and Drug Administration (FDA) regulations set forth in 21 Code of Federal 
Regulations (CFR) §50, 54, 56, and 312. 
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the evaluation and conduct of the clinical investigation without the prior 
written consent of Magenta. 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
Signature of Investigator 
Date 
Name/Address of Study Center: 


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PROCEDURES IN CASE OF EMERGENCY 
Please refer to the appropriate study materials for emergency contact information. 
 
Serious Adverse Event Reporting 
Refer to Section 11.2.3 for definitions and Section 11.5 for complete reporting requirements for 
serious adverse events (SAEs). 
Serious adverse events (initial and follow-up) must be reported to Magenta’s safety vendor 
(Premier) within 24 hours of awareness of the SAE or changes to an existing SAE. This should 
be done by emailing or faxing a signed copy of the SAE Report Form using the contact details 
below: 
Premier SAE Reporting Contact Details 
Email: 
 
 


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1. 
SYNOPSIS 
 
Name of Sponsor/Company: 
Magenta Therapeutics, Incorporated, Cambridge, MA 
Name of Investigational Product: 
MGTA-145 
Name of Active Ingredient: 
MGTA-145 (Gro Beta Truncate [GroβT], a CXC chemokine receptor 2 [CXCR2] agonist) 
Protocol Number: 
145-SCD-204 
Phase: Phase 2 
Country: United States (US) 
Title of Study: 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 
Study Center(s): Approximately 3 US study centers are planned for enrollment of subjects. 
Number of Subjects: Approximately 10 to 14 evaluable subjects are planned to be enrolled in 
this two-part study. 
• Part A has a planned enrollment of approximately 7 to 11 evaluable subjects. 
• Part B has a planned enrollment of approximately 3 evaluable subjects. 
Study Design: This is a two-part Phase 2, open-label, multicenter study. The study design is 
illustrated below. 
 
Methodology: Approximately 10 to 14 patients with sickle cell disease (SCD) are planned to be 
enrolled in this 2-part study. Part A evaluates single-day mobilization and apheresis in 2 
sequential patient cohorts, then Part B evaluates two-day mobilization and apheresis in a single 


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patient cohort, following administration of 2 consecutive-day single doses of MGTA-145 and 
plerixafor, respectively. 
Part A and Data Monitoring Committee (DMC) assessment: Part A has a planned 
enrollment of approximately 7 to 11 evaluable subjects. The first cohort of 4 subjects is 
to receive a single 0.24 mg/kg subcutaneous (SC) dose of plerixafor followed 2 hours 
later by a single 0.03 mg/kg intravenous (IV) dose of MGTA-145. Apheresis is planned 
to commence within approximately 30 minutes of MGTA-145 dosing. For this initial 
cohort, only one subject will be dosed and apheresed on a single-day, and each subject 
will complete the 1-week follow-up visit before a subsequent subject can be dosed. 
After the first cohort has completed the 1-week follow-up visit, an independent DMC, 
comprising of 3 members with medical expertise in stem cell transplantation and 
treatment of patients with SCD, will evaluate the safety, pharmacokinetics (PK), and 
mobilization kinetics of MGTA-145 before the second cohort of subjects is allowed to 
be enrolled. The DMC may recommend enrolling an additional 3 subjects at the 0.03 
mg/kg MGTA-145 dose, an additional 7 subjects at a reduced dose of 0.015 mg/kg 
MGTA-145, or an alternative but lower dosing regimen for this cohort. The MGTA-145 
dose will not be escalated during either Parts A or B of the study. 
After the second cohort has completed the 1-week follow-up visit, the DMC will 
likewise evaluate the safety, PK, and mobilization kinetics of MGTA-145 before 
subjects may be enrolled into Part B. Criteria for the DMC recommendations regarding 
cohort progression and dosing regimen will be defined in the DMC Charter. 
Part B: Part B has a planned enrollment of approximately 3 evaluable subjects. Subjects 
will receive single doses of MGTA-145 and plerixafor on 2 consecutive days, followed 
by apheresis on each dosing day. The dose of MGTA-145 will be identical to that of the 
second Part A cohort, unless otherwise recommended by the DMC. 
All subjects in Parts A and B will be observed at the investigational site from Day -1 until at 
least one day after the last apheresis, attend a 1-week follow-up visit 7 to 10 days after the last 
MGTA-145 infusion, and attend an end-of-study phone visit approximately 30 days after the 
last MGTA-145 infusion. 
Hematopoietic stem cells obtained by apheresis (HPC-A) will be processed according to 
standardized clinical cell therapy laboratory procedures. Peripheral blood and HPC-A will be 
stored for testing (e.g., exploratory pharmacodynamic (PD) evaluation, cell characterization, 
and process characterization) and approximately 2x106 CD34+ cells/kg are to be cryopreserved 
at clinical sites for potential future use by study subjects as backup reserve, should subjects 
decide to proceed with allogeneic hematopoietic cell transplant or autologous gene therapy. 
Overall Objectives: The overall objective of Part A is to investigate the efficacy, safety, 
tolerability, PK, and PD of a single dose of MGTA-145 for HSC mobilization and apheresis 
collection when given IV, in combination with plerixafor administered SC, to patients with 
SCD. 


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The overall objective of Part B is to investigate the efficacy, safety, tolerability, PK, and PD of 
MGTA-145 for HSC mobilization and apheresis collection when administered IV, in 
combination with plerixafor administered SC, to patients with SCD on 2 consecutive days, 
using the optimum MGTA-145 dose as determined during Part A. 
Objectives and Endpoints: Study objectives and associated endpoints for Part A are listed 
below: 
Part A Primary 
Objectives 
Part A Primary Endpoints 
To characterize the 
efficacy of a single dose 
of MGTA-145 and 
plerixafor for HSC 
mobilization and 
apheresis collection in 
patients with SCD 
• Determination of the yield of CD34+ cells (CD34+ cells/kg) 
after 1 dose of MGTA-145 and plerixafor followed by apheresis 
To characterize the safety 
and tolerability of 
MGTA-145 in patients 
with SCD 
• Incidence of TEAEs, including drug-related TEAEs, >Grade 3 
TEAEs, TESAEs, and TEAEs leading to study drug 
discontinuation 
• Incidence of treatment-emergent >Grade 3 clinical laboratory 
abnormalities 
• Clinically significant changes from baseline in vital signs and 
laboratory parameters (e.g., serum chemistry, hematology) 
Part A Secondary 
Objectives 
Part A Secondary Endpoints 
To measure the 
mobilization effects of 
single-day dosing with 
MGTA-145 and 
plerixafor in the 
peripheral blood in 
patients with SCD 
• Determination of peak peripheral blood CD34+ counts 
To characterize the PK 
profile of MGTA-145 in 
patients with SCD 
• Determination of PK exposures 
To characterize the 
immunogenicity of 
MGTA-145 in patients 
with SCD 
• Presence and titers of anti-drug antibodies 


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Part A Exploratory 
Objectives 
Part A Exploratory Endpoints 
To characterize the 
phenotype and function 
of cells collected by 
apheresis in patients with 
SCD 
• Flow cytometric characterization of cells collected following 
MGTA-145 and plerixafor mobilization and apheresis 
• Characterization of hematopoietic cell function by mouse 
engraftment studies and/or colony formation assays 
To assess gene- 
modifying potential of 
mobilized CD34+ cells in 
patients with SCD 
• Assessment of ability to select and gene-modify CD34+ cells 
HSC=hematopoietic stem cells; PD=pharmacodynamic(s); PK=pharmacokinetic(s); 
SCD=sickle cell disease; TEAE=treatment-emergent adverse event; TESAE=treatment- 
emergent serious adverse event 
Study objectives and associated endpoints for Part B are listed below: 
Part B Primary 
Objectives 
Part B Primary Endpoints 
To characterize the 
efficacy of 2 consecutive 
days of dosing with 
MGTA-145 and 
plerixafor for HSC 
mobilization and 
apheresis collection in 
patients with SCD 
• Determination of the yield of CD34+ cells after 2 consecutive 
days of MGTA-145 and plerixafor mobilization and apheresis 
collection in patients with SCD 
To characterize the safety 
and tolerability of 
MGTA-145 in patients 
with SCD 
• Incidence of TEAEs, including drug-related TEAEs, >Grade 3 
TEAEs, TESAEs, and TEAEs leading to study drug 
discontinuation 
• Incidence of treatment-emergent >Grade 3 clinical laboratory 
abnormalities 
• Clinically significant changes from baseline in vital signs and 
laboratory parameters (e.g., serum chemistry, hematology) 
Part B Secondary 
Objectives 
Part B Secondary Endpoints 
To measure the 
mobilization effects of 2 
consecutive days of 
• Determination of peak peripheral blood CD34+ counts 


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dosing with MGTA-145 
and plerixafor in the 
peripheral blood in 
patients with SCD 
To characterize the PK 
profile of MGTA-145 in 
patients with SCD 
• Determination of PK exposures 
To characterize the 
immunogenicity of 
MGTA-145 in patients 
with SCD 
• Presence and titers of anti-drug antibodies 
Part B Exploratory 
Objectives 
Part B Exploratory Endpoints 
To characterize the 
phenotype and function 
of cells collected by 
apheresis in patients with 
SCD 
• Flow cytometric characterization of the cells collected 
following MGTA-145 and plerixafor mobilization and 
apheresis 
• Characterization of hematopoietic cell function by mouse 
engraftment studies and/or colony formation assays 
To assess gene- 
modifying potential of 
mobilized HSC in 
patients with SCD 
• Assessment of the ability to select and gene-modify HSC 
HSC=hematopoietic stem cell; PD=pharmacodynamic(s); PK=pharmacokinetic(s); 
TEAE=treatment-emergent adverse event; TESAE=treatment-emergent serious adverse event 
Number of Subjects (planned): Approximately 10 to 14 evaluable subjects are planned in 
total. Part A has a planned enrollment of approximately 7 to 11, and Part B has a planned 
enrollment of approximately 3 evaluable subjects. 
Sample Size Justification: There are no statistical hypotheses in this trial, therefore there is no 
sample size calculation. To address the objectives assessing proof of concept of mobilizing 
CD34+ cells after 1 or 2 days of dosing with MGTA-145 and plerixafor, a minimum sample size 
of 10 evaluable subjects is considered adequate. 
Based on the safety profile including 79 subjects dosed with MGTA-145 in Phase 1 study 145- 
HV-101, 10 evaluable subjects are deemed a minimal number to assess common drug-related 
safety events. 
The most commonly observed adverse event (AE) in subjects treated with MGTA-145 is 
transient musculoskeletal pain, most often presenting as back pain occurring within 10 minutes 
of study treatment administration and generally resolving approximately 10 minutes later. -With 
10 evaluable subjects, there is sufficient subject exposure to assess for this AE. 


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Diagnosis and Criteria for Inclusion: 
1. Subject must be 18 to 35 years of age, inclusive. 
2. Subject must weigh ≥30 kg at screening. 
3. Subject must have a documented diagnosis of SCD with documentation of SCD 
genotype by medical history 
4. Subject must present with a feasible manual or automated exchange transfusion plan to 
achieve Hemoglobin S (HbS) <30% within 1 week of mobilization. 
5. Subject taking hydroxyurea must comply with a washout period of at least 30 days prior 
to mobilization dosing. Subjects must be able to safely discontinue hydroxyurea to 
participate in the study. 
6. Subject must have a local laboratory screening white blood cell (WBC) count >2.0 x 
109/L, absolute neutrophil count (ANC) >1.0 x 109/L, and platelet count >150 x 109/L. 
7. Subject must have a local laboratory screening estimated glomerular filtration rate 
(eGFR) of at least 60 mL/min/1.73 m2 based on the CKD-Epi equation. 
8. Subject must have a local laboratory screening alanine aminotransferase (ALT) value 
<2.5 x upper limit of normal (ULN). 
9. Subject’s cardiac and pulmonary status must be sufficient to undergo apheresis, as 
assessed by the Investigator. 
10. Subject must sign an Institutional Review Board (IRB)-approved informed consent form 
(ICF) and be willing to comply with the requirements of the protocol. 
Criteria for Exclusion for Parts A and B: 
1. Subject with a vaso-occlusive event (VOE) requiring a visit to a healthcare facility 
within 30 days prior to screening. 
2. Subject with onset of clinically apparent cerebrovascular accident (CVA) or retinal 
infarct within 2 years prior to screening or determined to be at high risk of CVA, based 
on concomitant disease (e.g., moyamoya), or imaging (e.g., trans-cranial doppler study). 
3. Subject with splenomegaly, splenic sequestration, sickle hepatopathy, priapism requiring 
inpatient treatment, acute chest syndrome requiring supplemental oxygen, or 
osteomyelitis within 6 months prior to screening. Subjects with a history of 
splenomegaly or splenic sequestration may be included if they have undergone a 
splenectomy. 
4. Subject having surgery requiring greater than local anesthesia within 3 months of 
screening, except for placement of a central venous access device. 
5. Subject who has received or plans to receive anticoagulation at the time of screening, 
except for study-related procedures. 


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6. Subject who, by medical history, requires rare donor registry red blood cell (RBC) units 
for transfusion, or is unable to receive routine transfusion. Eligible study subjects must 
have undergone prior work-up for the presence of red cell alloantibodies and 
confirmation of available compatible blood product support. 
7. Subject who has undergone or attempted and failed previous HSC collection. 
8. Subject who has had a prior autologous or allogeneic transplantation, inclusive of gene 
therapy. 
9. Subject who has received experimental therapy within 4 weeks prior to providing 
informed consent or is enrolled in another interventional experimental protocol. 
10. Subject with poorly controlled diabetes mellitus, as assessed by the Investigator. 
11. Subject who has an uncontrolled cardiovascular condition, including clinically 
significant cardiac arrhythmia, congestive heart failure, angina, myocardial infarction, or 
unstable pulmonary arterial hypertension within 6 months prior to screening. 
12. Subject with a history of or who has a positive screening laboratory test for human 
immunodeficiency disease (HIV), hepatitis B, hepatitis C, or human T-cell leukemia 
virus (HTLV). 
13. Subject with active infection or co-morbid condition that places the subject at high risk 
for treatment complications, as assessed by the Investigator. 
14. Subject with a known allergy to or contraindication for MGTA-145 or plerixafor 
administration, or medications routinely administered during apheresis. 
15. Male subject not willing or able to use a highly effective method of contraception for 3 
months during and after treatment with MGTA-145 and plerixafor, or female subject 
who is pregnant or breastfeeding, or sexually active and not willing or able to use a 
highly effective method of contraception for 3 months during and after treatment with 
MGTA-145 and plerixafor. 
Investigational Product, Dosage, and Mode of Administration: 
MGTA-145 injection is provided as a sterile solution for intravenous infusion in 2 mL Type I 
amber glass vials. MGTA-145 is formulated in 
 
. Each vial contains 1 mL of a 20 mg/mL 
solution. Up to two daily 0.03 mg/kg doses of MGTA-145 will be administered as a single 3- to 
10-minute IV infusion approximately 2 hours after 0.24 mg/kg SC administration of plerixafor. 
Plerixafor (injection) is provided as a sterile, preservative-free, clear, colorless to pale yellow, 
isotonic solution for SC injection. Each mL of the sterile solution contains 20 mg of plerixafor. 
Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of 
plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 
with hydrochloric acid and with sodium hydroxide, if required. 


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Duration of Treatment Part A: 
Screening Period: up to 30 days 
Dosing and Follow-up Period: approximately 30 days 
Duration of Treatment Part B: 
Screening Period: up to 30 days 
Dosing and Follow-up Period: approximately 30 days 
Reference Therapy, Dosage, and Mode of Administration: 
Not applicable 
Criteria for Evaluation: 
Safety: Subject safety will be assessed based on monitoring of AEs, vital signs, physical 
examinations, clinical laboratory evaluations, and development of anti-drug antibodies. Adverse 
events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0. 
Pharmacokinetics: PK samples will be collected for all subjects enrolled in Parts A and B at the 
timepoints outlined in the Schedules of Assessments. 
Pharmacodynamics: During Parts A and B, peripheral blood will be collected at the timepoints 
specified in the Schedule of Assessments to measure changes in CD34+ and 
CD34+CD90+CDRA- cell counts, as well as T-cell subtypes, B cells, monocytes, granulocytes, 
and natural killer (NK) cells. Cell counts will be analyzed using fluorescent flow cytometry. 
Changes in cell functionality will be assessed in terms of colony-forming units (CFUs) using an 
automated colony-counting device or manually with an inverted microscope. 
Statistical Methods: 
A formal statistical analysis plan (SAP) will be developed and finalized prior to database lock. 
This document will provide further details regarding the definition of analyses, any data 
handling conventions, and analyses methodology to address all study objectives. 
Statistical summaries will be descriptive in nature. All continuous variables will be summarized 
by dose cohort and visit (as applicable) using descriptive statistics (number of observations [n], 
mean, median, standard deviation [SD], minimum, and maximum). All categorical variables 
will be summarized by dose cohort and visit using frequency counts and percentages. Subjects 
who receive MGTA-145 will be included in the analyses. Data will be presented in aggregate 
and by cohort, if applicable. Subject baseline characteristics, including demographics and 
important disease characteristics, will be described using descriptive statistics. 
Primary Endpoint; Part A: 
• The CD34+ cells/kg apheresis yield with 1 apheresis session after MGTA-145 + 
plerixafor dosing will be presented at each dose of MGTA-145 evaluated. A mean yield 
and 95% confidence interval (CI) will be presented. 
• The number and percentage of subjects with administration-related toxicities and TEAEs 
will be summarized. 


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Primary Endpoint; Part B: 
• The total CD34+ cells/kg apheresis yield after 2 consecutive days of MGTA-145 + 
plerixafor mobilization and apheresis collection will be presented. A mean yield and 
95% CI will be presented. 
• The number and percentage of subjects with administration-related toxicities and TEAEs 
will be summarized. 
Secondary Endpoints; Parts A & B: 
Peak peripheral blood CD34+ counts will be summarized by time point relative to MGTA-145 
dosing. Apheresis collection yields after 2 consecutive days of mobilization will be summarized 
for Part B. 
Plasma concentrations of MGTA-145 will be listed, and a summary by time point for each dose 
cohort will be presented. Graphs of the individual subject concentration versus time profiles, as 
well as the arithmetic mean (±SD) concentration versus nominal time profiles, will be presented 
on a linear and log (concentration)/linear (time) scale. 
All exploratory endpoints will be analyzed using descriptive statistics as well as graphical 
methods, when appropriate. 


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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
SIGNATURE PAGE ........................................................................................................................ 2 
INVESTIGATOR’S AGREEMENT ............................................................................................... 3 
PROCEDURES IN CASE OF EMERGENCY ................................................................................ 4 
1. 
SYNOPSIS .................................................................................................................... 5 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ................ 14 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................. 20 
4. 
INTRODUCTION....................................................................................................... 23 
5. 
TRIAL OBJECTIVES AND PURPOSE .................................................................... 27 
5.1. 
Part A Objectives and Endpoints ................................................................................ 27 
5.2. 
Part B Objectives and Endpoints ................................................................................. 28 
6. 
INVESTIGATIONAL PLAN ..................................................................................... 30 
6.1. 
Overall Study Design .................................................................................................. 30 
6.2. 
Study Duration ............................................................................................................ 34 
6.2.1. 
Duration of Treatment Part A ..................................................................................... 34 
6.2.2. 
Duration of Treatment Part B ...................................................................................... 34 
6.3. 
Methodology ............................................................................................................... 34 
6.4. 
Number of Subjects ..................................................................................................... 35 
6.5. 
Treatment Assignment ................................................................................................ 35 
6.6. 
Stopping Rules ............................................................................................................ 36 
6.6.1. 
Scheduled Stopping Rule Assessments ....................................................................... 36 
6.6.1.1. 
Scheduled Part A, First Cohort DMC Stopping Rule Assessment ............................. 36 
6.6.1.2. 
Scheduled Part A, Second Cohort DMC Stopping Rule Assessment ......................... 37 
6.6.1.3. 
Unscheduled Stopping Rule Assessment .................................................................... 37 
6.7. 
Criteria for Study Stopping/Termination ..................................................................... 37 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS .............................................. 39 
7.1. 
Criteria for Inclusion for Parts A and B ...................................................................... 39 
7.2. 
Criteria for Exclusion for Parts A and B ..................................................................... 39 
7.3. 
Subject Withdrawal Criteria ........................................................................................ 40 
8. 
TREATMENT OF SUBJECTS .................................................................................. 42 


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8.1. 
Description of Study Drug ......................................................................................... 42 
8.1.1. 
Dose Cohort(s) Planned for Part A ............................................................................ 42 
8.1.2. 
Dose Cohort Planned for Part B ................................................................................. 42 
8.2. 
Concomitant Medications and Supportive Care ........................................................ 42 
8.3. 
Treatment Compliance ............................................................................................... 42 
8.4. 
Randomization and Blinding ..................................................................................... 43 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT ........................................... 44 
9.1. 
Study Drug ................................................................................................................. 44 
9.2. 
Study Drug Packaging and Labeling ......................................................................... 44 
9.3. 
Study Drug Storage and Stability ............................................................................... 44 
9.4. 
Study Drug Preparation .............................................................................................. 45 
9.5. 
MGTA-145 and Plerixafor Administration ................................................................ 45 
9.6. 
Study Drug Accountability......................................................................................... 45 
9.7. 
Study Drug Handling and Disposal ........................................................................... 45 
10. 
PHARMACOKINETIC, PHARMACODYNAMIC, AND IMMUNOLOGIC 
ASSESSMENTS ........................................................................................................ 46 
10.1. 
Pharmacokinetic Assessments ................................................................................... 46 
10.2. 
Pharmacodynamic Assessments ................................................................................. 46 
10.2.1. 
Colony-Forming Unit Analysis .................................................................................. 46 
10.2.2. 
Apheresis Yield .......................................................................................................... 46 
10.2.2.1. 
Peripheral Blood CD34+ Counts ................................................................................ 46 
10.2.2.2. 
Exploratory Graft Characterization ............................................................................ 47 
10.3. 
Immunologic Assessments ......................................................................................... 47 
11. 
ASSESSMENT OF SAFETY .................................................................................... 48 
11.1. 
Safety Parameters ....................................................................................................... 48 
11.1.1. 
Demographic Information .......................................................................................... 48 
11.1.2. 
Medical History.......................................................................................................... 49 
11.1.3. 
Vital Signs .................................................................................................................. 49 
11.1.4. 
Weight and Height ..................................................................................................... 49 
11.1.5. 
Physical Examination (Complete and Symptom-directed) ........................................ 49 
11.1.6. 
Electrocardiogram ...................................................................................................... 49 
11.1.7. 
Clinical Laboratory Assessments ............................................................................... 49 
11.1.7.1. 
Hematology ................................................................................................................ 50 


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11.1.7.2. 
Clinical Chemistry ...................................................................................................... 50 
11.1.7.3. 
Urinalysis .................................................................................................................... 50 
11.1.7.4. 
Virus Serology ............................................................................................................ 50 
11.1.7.5. 
Pregnancy Screen ........................................................................................................ 50 
11.1.8. 
Patient Surveys ............................................................................................................ 50 
11.1.8.1. 
ASCQ-ME® ......................................................................................................................................................................50 
11.1.8.2. 
PROMIS®...........................................................................................................................................................................51 
11.1.9. 
EOS Phone Visit ......................................................................................................... 51 
11.2. 
Adverse Events and Serious Adverse Events .............................................................. 51 
11.2.1. 
Adverse Events ........................................................................................................... 51 
11.2.2. 
Adverse Event Definition ............................................................................................ 51 
12. 
STATISTICS .............................................................................................................. 56 
12.1. 
Analysis Sets ............................................................................................................... 56 
12.2. 
Subject Demographic and Other Baseline Characteristics .......................................... 56 
12.3. 
Exposure and Concomitant Medications..................................................................... 56 
12.4. 
Analysis of the Primary, Secondary, and Exploratory Endpoints ............................... 56 
12.4.1. 
Statistical Methods and Analyses ............................................................................... 56 
12.4.2. 
Safety .......................................................................................................................... 57 
12.4.3. 
Pharmacokinetics ........................................................................................................ 57 
12.4.4. 
Pharmacodynamics ...................................................................................................... 57 
12.5. 
Sample Size Calculation ............................................................................................. 57 
13. 
DATA REVIEW AND DATABASE MANAGEMENT ........................................... 58 
13.1. 
Study Site Monitoring ................................................................................................. 58 
13.2. 
Data Collection............................................................................................................ 58 
13.3. 
Database Management and Quality Control ............................................................... 59 
13.4. 
Audits and Inspections ................................................................................................ 59 
13.5. 
Monitoring Committees .............................................................................................. 59 
14. 
ETHICS ....................................................................................................................... 60 
14.1. 
Ethics Review ............................................................................................................. 60 
14.2. 
Ethical Conduct of the Study ...................................................................................... 60 
14.3. 
Written Informed Consent .......................................................................................... 60 
15. 
DATA HANDLING AND RECORD KEEPING ....................................................... 61 
15.1. 
Inspection of Records .................................................................................................. 61 


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15.2. 
Retention of Records ................................................................................................... 61 
16. 
PUBLICATION POLICY ........................................................................................... 62 
17. 
LIST OF REFERENCES ............................................................................................ 63 
18. 
APPENDICES ............................................................................................................ 65 
18.1. 
CKD-EPI Equation ..................................................................................................... 65 
18.2. 
Patient Surveys ............................................................................................................ 65 
18.2.1. 
Adult Sickle Cell Quality of Life Measurement Information®; v2.0 .......................... 65 
18.2.1.1. 
Emotional Impact Domain .......................................................................................... 65 
18.2.1.2. 
Pain Impact Domain.................................................................................................... 66 
18.2.1.3. 
Sleep Impact Domain .................................................................................................. 67 
18.2.1.4. 
Social Functioning Domain ........................................................................................ 68 
18.2.1.5. 
Stiffness Impact Domain ............................................................................................. 69 
18.2.2. 
PROMIS®-57 Profile v2.1 (Pain Interference and Pain Intensity Domains) .............. 71 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms .......................................................................... 20 
Table 2: 
Adverse Events Observed with MGTA-145 and Plerixafor in Phase 1 Study 
145-HV-101 ............................................................................................................... 25 
Table 3: 
Median peak CD34+ Counts Observed After Administration of Various 
Doses of MGTA-145 with Plerixafor–Data from Phase I Study 145-HV-101 .......... 26 
Table 4: 
Part A Objectives and Endpoints ............................................................................... 27 
Table 5: 
Part B Objectives and Endpoints ................................................................................ 28 
Table 6: 
Schedule of Assessments: Part A (Single Dose) ........................................................ 31 
Table 7: 
Schedule of Assessments: Part B (Single Dose on 2 Consecutive Days) .................. 33 
Table 8: 
Schedule of Assessments (Parts A and B) – Blood and Immune Cell 
Composition ............................................................................................................... 34 
Table 9: 
Probabilities of Grade 3 VOEs Occurring in Given Numbers of Study 
Subjects Undergoing Apheresis in the First Patient Cohort of Part A, if 
Mobilized with Plerixafor Alone ............................................................................... 36 
Table 10: Probabilities of Grade 3 VOEs Occurring in Given Numbers of Study 
Subjects Undergoing Apheresis in the Second Patient Cohort of Part A, if 
Mobilized with Plerixafor Alone ............................................................................... 37 
Table 11: 
Study Drug ................................................................................................................. 44 


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LIST OF FIGURES 
Figure 1: 
Part A (Single Dose) and Part B (Single Dose on 2 Consecutive Days) .................... 30 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms 
 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ASCQ-Me® 
Adult Sickle Cell Quality of Life Measurement 
Information System 
β-hCG 
Beta-human chorionic gonadotropin 
CBC 
Complete blood count 
CD-ROM 
Compact disc read-only memory 
CFR 
Code of Federal Regulations 
CFU 
Colony-forming unit 
CFU-GM 
Granulocyte-macrophage colony-forming unit 
CFU-GEMM 
Granulocyte-erythrocyte-macrophage-megakaryocyte 
colony-forming unit 
CI 
Confidence interval 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVA 
Cerebrovascular accident 
CXCL2 
CXC chemokine ligand 2 
CXCR2 
CXC chemokine receptor 2 
CXCR4 
CXC chemokine receptor 4 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
ECLIA 
Electrochemiluminescent immunoassay 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EOS 
End of study 
eGFR 
Estimated glomerular filtration rate 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 


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Abbreviation or Specialist Term 
Explanation 
G-CSF 
Granulocyte-colony stimulating factor 
GroβT 
Gro Beta Truncate 
HbS 
Hemoglobin S 
HBsAg 
Hepatitis B surface antigen 
HIV 
Human immunodeficiency virus 
HPC-A 
Hematopoietic stem cells obtained by apheresis 
HSC 
Hematopoietic stem cells 
HSCT 
Hematopoietic stem cell transplantation 
HTLV 
Human T-cell leukemia virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMP-9 
Matrix metallopeptidase 9 
NCI 
National Cancer Institute 
NK 
Natural killer (cells) 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic(s) 
PK 
Pharmacokinetic(s) 
PROMIS® 
Patient-Reported Outcomes Measurement Information 
System 
PT 
Preferred term 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 


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Abbreviation or Specialist Term 
Explanation 
SCD 
Sickle Cell Disease 
SD 
Standard deviation 
SDF-1α 
Stromal-derived factor-1α 
SEM 
Standard error of the mean 
SOC 
System organ class 
SUSAR 
Suspected unexpected serious adverse event 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
ULN 
Upper limit of normal 
US 
United States 
USB 
Universal serial bus 
VOE 
Vaso-occlusive event 
WBC 
White blood cell 


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4. 
INTRODUCTION 
With prevalence estimated to be at least 20 million globally and 100,000 in the United States 
(US),1 sickle cell disease (SCD) is the most common inherited blood disorder in much of the 
world.2 Sickle cell disease is caused by an autosomal recessive point mutation in the β-globin 
gene HBB, resulting in abnormal β-globin protein (hemoglobin SS disease), or by compound 
heterozygosity of hemoglobin S with another β-globin chain abnormality, e.g., hemoglobin C or 
β-thalassemia. Owing to the relative protection against malaria conferred by the heterozygotic 
state, SCD is largely distributed in populations originating from sub-Saharan Africa, Middle 
East, and the Indian subcontinent, in areas where malaria prevalence is high. In the US, 
approximately one in 400 to 700 African Americans is born with SCD.1,3 
The formation of abnormal hemoglobin tetramers, which polymerize into filaments under low 
oxygen tension, results in deformable, sickle-shaped erythrocytes with abnormal rheology, 
leading to vaso-occlusion, ischemic tissue damage, and hemolysis-associated endothelial 
dysfunction.4 Patients with SCD are vulnerable to bacterial infections, largely due to splenic 
dysfunction, and frequently suffer lifelong pain and fatigue.5 Pain is the leading cause of US 
hospitalizations for patients with SCD, with an estimated burden of $1.1 billion, and is 
associated with poor health-related quality of life and early mortality.6,7 Patients with SCD 
demonstrate higher rates of healthcare utilization, as manifest by emergency department 
utilization, hospitalization, and readmission rates, each correlating with age and SCD-related 
complications.8 
Neonatal screening for SCD, performed routinely prior to hospital discharge, permits early 
medical intervention (e.g., penicillin prophylaxis for patients <5 years old), thereby reducing 
early morbidity and mortality of SCD. Other treatments, including hydroxyurea, blood 
transfusions, and pain medications including opioids, are largely palliative and unfortunately, 
many patients generally still have a poor quality of life due to recurring painful vaso-occlusive 
events (VOEs) and subsequent end-organ damage. While newer medications (e.g., L-glutamine, 
voxelotor, crizanlizumab) may improve mortality as well as morbidity of the disease, it is 
nonetheless estimated that most patients with SCD will not live beyond their fifth or sixth 
decade.9 
Since first performed in 1984,10 allogeneic hematopoietic cell transplantation has demonstrated 
the potential for cure or long-term amelioration of SCD, with long-term overall and event-free 
survival rates of more than 90%.11 However, considering the potential for serious and potentially 
life-threatening side effects, use of hematopoietic stem cell transplantation (HSCT) is limited to 
patients with severe SCD in whom potential benefits outweigh the risk of the procedure (e.g., 
patients with a history of stroke, acute chest syndrome, recurrent pain crisis requiring exchange 
transfusions, nephropathy, retinopathy, osteonecrosis of multiple joints, priapism). Allogeneic 
transplant incurs notable risks of graft-versus-host disease and graft rejection,12 and requires a 
matching bone marrow or stem cell donor, which has further limited utilization in this 
population.13,14 
Early results of autologous HSCT, using addition of a non-sickling gene or gene editing to 
increase fetal hemoglobin, suggest that this approach may provide a favorable option for patients 
with SCD. However, while peripheral blood collection is preferable to bone marrow harvest of 
HSCs, mobilization of HSCs with granulocyte-colony stimulating factor (G-CSF) has been 


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associated with severe sickle cell crises and death in patients with SCD or trait.15,16 Licensed in 
the US since 2008, plerixafor (Mozobil®, Genzyme) is a small molecule, reversible antagonist of 
chemokine receptor 4 (CXCR4), currently indicated to be used in combination with G-CSF to 
mobilize HSCs to the peripheral blood for collection and subsequent autologous transplantation 
in patients with multiple myeloma and non-Hodgkin’s lymphoma.17 Plerixafor acts by disrupting 
binding to the receptor’s cognate ligand, stromal-derived factor-1α (SDF-1α) chemokine ligand 
12 (CXCL12), thereby resulting in mobilization of CD34+ HSCs into the peripheral blood. More 
recently, plerixafor alone has demonstrated efficacy in the mobilization of sufficient HSC for 
collection in patient populations, including SCD.18,19,20 However, as many as 75% of patients 
with SCD require 2 or more cycles of multi-day plerixafor administration and apheresis in order 
to collect sufficient HSCs for genetic modification and infusion, and vaso-occlusive crisis 
remains a risk with each mobilization and apheresis procedure,21 with approximately 30% of 
plerixafor-mobilized patients reported to have experienced VOEs of at least Grade 3 severity 
during and after harvesting, and approximately 20% of patients reported to have experienced 
serious vaso-occlusive pain within 2 days post-procedure. Hypomagnesemia, hypokalemia, and 
hypocalcemia have also been reported commonly among patients with SCD mobilized with 
plerixafor, although most events were Grade 1 or 2 in severity. Approximately half of patients 
with SCD require opioid medications within a week prior or subsequent to mobilization and 
apheresis.22 Nonetheless, mobilization with plerixafor seems to result in an apheresis product 
superior to bone marrow harvest, based on the concentration of high-quality CD34+ HSCs most 
suitable for ex vivo manipulation and autologous transplantation.22 
Magenta Therapeutics, Inc. (Magenta) is developing MGTA-145 for the mobilization of CD34+ 
cells when used in combination with plerixafor. MGTA-145 (aka Gro Beta Truncate or GroβT) 
is a 4 amino acid-truncated protein variant of CXC chemokine ligand 2 (CXCL2), an agonist of 
cell-surface chemokine receptor CXC chemokine receptor 2 (CXCR2). MGTA-145 mobilization 
is mediated by matrix metallopeptidase-9 (MMP-9). After MGTA-145 binds to CXCR2, MMP-9 
is released from neutrophils, resulting in the cleavage of adhesive molecules that tether HSCs to 
the bone marrow niche. The addition of plerixafor, an antagonist of CXCR4, inhibits cross- 
communication between CXCR4 and CXCR2 receptors which normally function to diminish the 
CXCR2 response. The addition of plerixafor helps enhance the release of MMP-9, leading to 
increased mobilization of hematopoietic cells. 
Preclinical studies in mice, rats, and non-human primates demonstrated that MGTA-145, when 
administered simultaneously with plerixafor, leads to rapid and robust mobilization of CD34+ 
cells, including CD34+CD90+CD45RA- cells within minutes to hours. 
Phase I study 145-HV-101 evaluated MGTA-145 administered with or without plerixafor to 79 
healthy volunteers, to determine the safety and dose of MGTA-145. The study had 4 parts. In 
Part A, subjects received a single dose of MGTA-145 alone (0.0075 to 0.3 mg/kg). In Part B, 
subjects received a single dose of MGTA-145 (0.015 to 0.15 mg/kg) with plerixafor. In Part C, 
subjects received 2 daily doses of MGTA-145 (0.03 and 0.07 mg/kg) and plerixafor. In Part D, 
subjects received a single dose of MGTA-145 (0.015 or 0.03 mg/kg) and plerixafor, followed by 
same-day apheresis. MGTA-145 was found to have acceptable safety and tolerability, with the 
most common side effect being transient back pain, lasting less than 20 minutes in most patients. 
In Part A, back pain was seen in 79% (19/24) of volunteers receiving single agent MGTA-145 
vs. 0% (0/12) of volunteers receiving plerixafor. There were no other treatment-emergent 


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adverse effects (TEAE) observed among subjects in Part A receiving MGTA-145 (0.0075 to 
0.3 mg/kg). When MGTA-145 (0.015 to 0.15 mg/kg) was combined with plerixafor in Part B, 
TEAE were observed in 81% of subjects, compared to 57% of patients receiving plerixafor 
alone. TEAE in the MGTA-145 and plerixafor arm included back pain/musculoskeletal pain in 
63%, nausea in 18%, diarrhea and dizziness in 16% each, abdominal pain in 13%, headache in 
11%, vomiting in 8%, and paresthesia in 5% of subjects. This data is shown in Table 2 below. 
Table 2: 
Adverse Events Observed with MGTA-145 and Plerixafor in Phase 1 Study 
145-HV-101 
 
 
 
At the 0.03 mg/kg dose, the peak median CD34+ cell count in peripheral blood following 
MGTA-145 and plerixafor administration was 40 cells/μL (range 18 to 63), which was higher 
than that observed with plerixafor alone (median 24, range: 13 to 78). The dose of 0.03 mg/kg 
was determined to be safe and effective, with predictable, dose-linear pharmacokinetics (PK) that 
are not affected by the coadministration of plerixafor. Administration of plerixafor followed by 
MGTA-145 after a 2-hour interval was associated with better stem cell mobilization outcomes 
than administration of plerixafor followed by MGTA-145 after a 10-minute interval, as 
determined by peripheral blood CD34+ cell counts, and will therefore be the regimen used in this 
trial. 
The median peak CD34+ cell counts observed after administration of various doses of 
MGTA-145 with plerixafor is provided in Table 3. 
Importantly for patients with SCD, for whom substantial apheresis yields of up to 15x106 CD34+ 
cells/kg or more may be required for successful genetic modification and subsequent aHSCT, the 
0.03 mg/kg dose of MGTA-145 resulted in the highest median peripheral CD34+ cell count (40 
cells/μL (range 18 to 63), as shown in Table 3. 
Likewise important for patients with SCD, Phase 1 evaluation demonstrated limited neutrophil 
activation following MGTA-145 administration, based on changes in L-selectin, CD11b, CD18, 


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and CD66 from baseline. In the 145-HV-101 study, the 0.03 mg/kg dose of MGTA-145 
demonstrated the least change from baseline for these markers of neutrophil activation. Thus, 
MGTA-145 0.03 mg/kg, in combination with plerixafor 0.24 mg/kg, represents the optimal 
dosing regimen in patients with SCD, both with regard to subject safety and anticipated 
mobilization response. Evaluation of the optimal MGTA-145 dose in patients with SCD will 
provide the greatest opportunity to minimize the number of apheresis sessions required to 
reliably collect sufficient HSCs, and likely minimize inter-subject variability in mobilization 
responses, where patients who mobilize poorly may gain incremental benefit from the 0.03 
mg/kg dose. Based on similar rationale, investigator-initiated Phase 2 PoC study BMT-362 
(conducted under IND 151874) evaluated and has demonstrated that administration of 0.03 
mg/kg MGTA-145 in combination with plerixafor safely and successfully mobilizes HSCs for 
collection in patients with multiple myeloma undergoing aHSCT.23 
Table 3: 
Median peak CD34+ Counts Observed After Administration of Various 
Doses of MGTA-145 with Plerixafor–Data from Phase I Study 145-HV-101 
 
Mobilization 
Regimen 
MGTA-145 Dose 
(mg/kg) 
Peak CD34+ Count/µL 
Median (Range) 
MGTA-145 + Plerixafor 
0.07 
26 (11 to 42) 
0.03 
40 (18 to 63) 
0.015 
36 (18 to 86) 
Placebo + Plerixafor 
0 
26 (13 to 78) 
A regimen of MGTA-145 in combination with plerixafor may provide the potential for greater 
yield of HSCs, requiring a shorter duration/number of mobilization and apheresis cycles, with 
improved safety and tolerability in patients with SCD as well as other inherited disorders for 
which future genetic modification and autologous transplantation may prove curative. Therefore, 
this Phase 2 PoC study evaluates the efficacy and safety of MGTA-145, administered 
concomitantly with plerixafor, to patients with SCD for the purpose of HSC mobilization and 
collection via apheresis. 
While patients may benefit from participation in the study (apheresis product will be stored by 
the investigational sites for potential future transplantation), there is no immediate individual 
clinical benefit to patients who agree to participate in this study. The study is anticipated to yield 
important generalizable knowledge about mobilization and apheresis using MGTA-145 in the 
SCD patient population. The study population is therefore planned to include patients 18 to 35 
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5. 
TRIAL OBJECTIVES AND PURPOSE 
The overall objective of Part A is to investigate the efficacy, safety, tolerability, PK, and 
pharmacodynamics (PD) of a single dose of MGTA-145 for HSC mobilization and apheresis 
collection when given intravenously (IV) in combination with plerixafor administered SC to 
patients with SCD. 
The overall objective of Part B is to investigate the efficacy, safety, tolerability, PK, and PD of 
MGTA-145 for HSC mobilization and apheresis collection when given IV in combination with 
plerixafor administered SC to patients with SCD on 2 consecutive days, using the optimum 
MGTA-145 dose as determined during Part A. 
5.1. 
Part A Objectives and Endpoints 
Study objectives and associated endpoints for Part A are listed in Table 4: 
Table 4: 
Part A Objectives and Endpoints 
 
Part A Primary 
Objectives 
Part A Primary Endpoints 
To characterize the 
efficacy of a single dose 
of MGTA-145 and 
plerixafor for HSC 
mobilization and 
apheresis collection in 
patients with SCD 
• Determination of the yield of CD34+ cells (CD34+ cells/kg) after 
1 dose of MGTA-145 and plerixafor followed by apheresis 
To characterize the safety 
and tolerability of 
MGTA-145 in patients 
with SCD 
• Incidence of TEAEs, including drug-related TEAEs, >Grade 3 
TEAEs, TESAEs, and TEAEs leading to study drug 
discontinuation 
• Incidence of treatment-emergent >Grade 3 clinical laboratory 
abnormalities 
• Clinically significant changes from baseline in vital signs and 
laboratory parameters (e.g., serum chemistry, hematology) 
Part A Secondary 
Objectives 
Part A Secondary Endpoints 
To measure the 
mobilization effects of 
single-day dosing with 
MGTA-145 and 
plerixafor in the 
peripheral blood in 
patients with SCD 
• Determination of peak peripheral blood CD34+ counts 


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To characterize the PK 
profile of MGTA-145 in 
patients with SCD 
• Determination of PK exposures 
To characterize the 
immunogenicity of 
MGTA-145 in patients 
with SCD 
• Presence and titers of anti-drug antibodies 
Part A Exploratory 
Objectives 
Part A Exploratory Endpoints 
To characterize the 
phenotype and function of 
cells collected by 
apheresis in patients with 
SCD 
• Flow cytometric characterization of cells collected following 
MGTA-145 and plerixafor mobilization and apheresis 
• Characterization of hematopoietic cell function by mouse 
engraftment studies and/or colony formation assays 
To assess gene-modifying 
potential of mobilized 
CD34+ cells in patients 
with SCD 
• Assessment of ability to select and gene-modify CD34+ cells 
HSC=hematopoietic stem cells; PD=pharmacodynamic(s); PK=pharmacokinetic(s); 
SCD=sickle cell disease; TEAE=treatment-emergent adverse event; TESAE=treatment- 
emergent serious adverse event 
5.2. 
Part B Objectives and Endpoints 
Study objectives and associated endpoints for Part B are listed in Table 5: 
Table 5: 
Part B Objectives and Endpoints 
 
Part B Primary 
Objectives 
Part B Primary Endpoints 
To characterize the 
efficacy of 2 consecutive 
days of dosing with 
MGTA-145 and 
plerixafor for HSC 
mobilization and 
apheresis collection in 
patients with SCD 
• Determination of the yield of CD34+ cells after 2 consecutive 
days of MGTA-145 and plerixafor mobilization and apheresis 
collection in patients with SCD 
To characterize the safety 
and tolerability of 
• Incidence of TEAEs, including drug-related TEAEs, >Grade 3 
TEAEs, TESAEs, and TEAEs leading to study drug 
discontinuation 


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MGTA-145 in patients 
with SCD 
• Incidence of treatment-emergent >Grade 3 clinical laboratory 
abnormalities 
• Clinically significant changes from baseline in vital signs and 
laboratory parameters (e.g., serum chemistry, hematology) 
Part B Secondary 
Objectives 
Part B Secondary Endpoints 
To measure the 
mobilization effects of 2 
consecutive days of 
dosing with MGTA-145 
and plerixafor in the 
peripheral blood in 
patients with SCD 
• Determination of peak peripheral blood CD34+ counts 
To characterize the PK 
profile of MGTA-145 in 
patients with SCD 
• Determination of PK exposures 
To characterize the 
immunogenicity of 
MGTA-145 in patients 
with SCD 
• Presence and titers of anti-drug antibodies 
Part B Exploratory 
Objectives 
Part B Exploratory Endpoints 
To characterize the 
phenotype and function of 
cells collected by 
apheresis in patients with 
SCD 
• Flow cytometric characterization of the cells collected following 
MGTA-145 and plerixafor mobilization and apheresis 
• Characterization of hematopoietic cell function by mouse 
engraftment studies and/or colony formation assays 
To assess gene-modifying 
potential of mobilized 
HSC in patients with 
SCD 
• Assessment of the ability to select and gene-modify CD34+ 
cells 
HSC=hematopoietic stem cell; PD=pharmacodynamic(s); PK=pharmacokinetic(s); 
TEAE=treatment emergent adverse event; TESAE=treatment-emergent serious adverse event 


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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
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 intended 
to characterize the efficacy of 2 consecutive days of dosing with MGTA-145 and plerixafor for 
HSC mobilization and apheresis collection in patients with SCD. 
The study design and subject procedural flow schematic for Parts A and B are illustrated in 
Figure 1. The Schedule of Assessments for Part A is provided in 
Table 6, and the Schedule of Assessments for Part B is provided in Table 7. The Schedule of 
Assessments for blood and immune cell composition for Parts A and B is provided in Table 8. 
Figure 1: 
Part A (Single Dose) and Part B (Single Dose on 2 Consecutive Days) 
 


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Table 6: 
Schedule of Assessments: Part A (Single Dose) 
 
Study Period Procedures 
Screening 
Baseline 
Mobilization 
/Apheresis 
1-week 
follow-up 
(Day 7 to 
10)b 
End of 
Study 
(Day 30)b 
Day -30 to -2 
Day -1 
Day 1 
Informed consent 
X 
Medical history 
X 
X 
Inclusion/exclusion criteria 
review 
X 
Height 
X 
Weight 
X 
X 
Physical examination 
X 
X 
X 
Symptom-directed physical 
examination 
X 
Vital signs a 
X 
X 
X 
X 
Serology c 
X 
Serum or urine β-hCG (females) 
X 
X 
12-lead ECG 
X 
Urinalysis 
X 
X 
X 
Chemistry d 
X 
X 
X 
X 
Hematology e 
X 
X 
X 
X 
Anti-drug antibodies 
X 
X 
Plerixafor administration 
X 
MGTA-145 administration f 
X 
Apheresis procedure 
X 
Apheresis yield g 
X 
PROMIS and ASCQ-Me 
questionnaires h 
X 
X 
Non-serious AEs and SAEs i 
X 
X 
X 
X 
Xj 
Concomitant medications 
X 
X 
X 
X 
Xj 
AE=adverse event; ASCQ-Me=Adult Sickle Cell Quality of Life Measurement Information; BPI=Brief Pain Inventory; β-hCG=beta- 
human chorionic gonadotropin; CFU= colony-forming unit; ECG=electrocardiogram; PK=pharmacokinetics; NRS=Numeric Rating 
Scale; SAE=serious adverse event 
a Vital sign measurements will be taken in the sitting position after the subject has been resting for 5 minutes. Vital signs should be taken 
before any blood samples are drawn. 
b If a subject does not complete dosing, there will not be follow-up visits. If a subject received MGTA-145 but did not complete apheresis, 
then follow-up visits are required. 
cAll subjects enrolled in Parts A will be screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), human 
T-cell leukemia virus (HTLV), and hepatitis C virus (HCV) at the screening visit. Subjects who are HCV antibody positive must have a 
HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) test. 
d Clinical chemistry consists of sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, total and indirect bilirubin. Clinical chemistry 
sample collection should be done prior to dosing on Day 1. All other clinical chemistry sample collections will be done on the morning 
of the assessment day. 
e Hematology is complete blood count (CBC) with platelets and leukocyte differential. Hematology sample collection should be done 
prior to dosing on Day 1 and Day 2. All other hematology sample collections will be done on the morning of the assessment day. 
f MGTA-145 is to be administered via a 3 to 10-minute IV infusion, approximately 2 hours after plerixafor SC injection. Instructions 
regarding administration are provided in the Study Pharmacy Manual. 
g Total nucleated cell count and CD34+ cell count in absolute numbers and per kg. 
h ASCQ-Me® and PROMIS® questionnaires will be completed prior to dosing on Day 1. 


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i Collection of non-serious AEs and SAEs will begin once the Informed Consent Form (ICF) has been signed. Any SAE occurring after 
the reporting period must be promptly reported if a causal relationship to study drugs is suspected. 
j End-of-study visit phone call will occur 30 days (±3 days) after the last dose of MGTA-145 was received, to assess adverse events and 
concomitant medications. 


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Table 7: 
Schedule of Assessments: Part B (Single Dose on 2 Consecutive Days) 
 
Study Period Procedures 
Screening 
Baseline 
Mobilization/Apheresis b 
1-week 
follow- 
up (Day 
8 to 11)c 
End of 
Study 
(Day 
30)c 
Day -30 to 
-2 
Day -1 
Day 1 
Part B 
Day 2 
Part B 
only 
Informed consent 
X 
Medical history 
X 
X 
Inclusion/exclusion criteria 
review 
X 
Height 
X 
Weight 
X 
X 
Physical examination 
X 
X 
X 
Symptom-directed physical 
examination 
X 
X 
Vital signs a 
X 
X 
X 
X 
X 
Serology d 
X 
Serum or urine β-hCG 
(females) 
X 
X 
12-lead ECG 
X 
Urinalysis 
X 
X 
X 
X 
Chemistry e 
X 
X 
X 
X 
X 
Hematology f 
X 
X 
X 
X 
X 
Anti-drug antibodies 
X 
X 
Plerixafor administration 
X 
X 
MGTA-145 administration g 
X 
X 
Apheresis procedure 
X 
X 
Apheresis yield h 
X 
X 
PROMIS and ASCQ- 
questionnaires i 
X 
X 
Non-serious AEs and SAEs j 
X 
X 
X 
X 
X 
Xk 
Concomitant medications 
X 
X 
X 
X 
X 
Xk 
AE=adverse event; ASCQ-Me=Adult Sickle Cell Quality of Life Measurement Information; BPI=Brief Pain Inventory; β-hCG=beta- 
human chorionic gonadotropin; CFU= colony-forming unit; ECG=electrocardiogram; PK=pharmacokinetics; NRS=Numeric Rating Scale; 
SAE=serious adverse event 
a Vital sign measurements will be taken in the sitting position after the subject has been resting for 5 minutes. Vital signs should be taken 
before any blood samples are drawn. 
b For Part B, mobilization/collection will occur on 2 consecutive days. 
c If a subject does not complete dosing, there will not be follow-up visits. If a subject received MGTA-145 but did not complete apheresis, 
then follow-up visits are required. 
d All subjects enrolled in Part B will be screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), human T- 
cell leukemia virus (HTLV), and hepatitis C virus (HCV) at the screening visit. Subjects who are HCV antibody positive must have a 
HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) test. 
e Clinical chemistry consists of sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, total and indirect bilirubin. Clinical chemistry 
sample collection should be done prior to dosing on Day 1 and Day2. All other clinical chemistry sample collections will be done on the 
morning of the assessment day. 
f Hematology is complete blood count (CBC) with platelets and leukocyte differential. Hematology assessments will be done on the 
morning of the assessment day. 


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Table 8: 
Schedule of Assessments (Parts A and B) – Blood and Immune Cell 
Composition 
 
Assessments 
Day 1 (Parts A and B) and Repeated on Day 2 (Part B Only) 
Within 1 
Hour 
Prior to 
Plerixafor 
Dosing 
1 Hour 
After 
Plerixafor 
Dosing 
Within 
15 Min 
Prior to 
MGTA 
Dosing 
Post MGTA-145 Dosing 
Apheresis 
Product a 
30 Min 
Prior 
to 
Apheresis 
15 Min 
Prior 
to 
Apheresis 
5 Min 
Prior to 
Apheresis 
Peripheral Blood CD34+ 
analysis 
X 
X 
X 
X 
Graft 
Immunophenotyping 
X a 
PK blood samples b 
X 
X 
X 
X b 
CFU analysis 
X a 
a Samples will be aliquoted from final HPA-C 
b PK time points are within 15 minutes prior to MGTA-145 dosing and at 2 time points, spaced at least 15 minutes apart, prior to the 
initiation of apheresis. If apheresis is not initiated within 45 minutes of MGTA-145 dosing, a third PK sample is to be drawn within 5 
minutes prior initiation of apheresis. 
6.2. 
Study Duration 
6.2.1. 
Duration of Treatment Part A: 
Screening Period: up to 30 days 
Dosing and Follow-up Period: approximately 30 days 
6.2.2. 
Duration of Treatment Part B: 
Screening Period: up to 30 days 
Dosing and Follow-up Period: approximately 30 days 
6.3. 
Methodology 
Approximately 10 to 14 patients with SCD are planned to be enrolled in this 2-part study. Part A 
evaluates single-day mobilization and apheresis in 2 sequential patient cohorts, then Part B 
evaluates two-day mobilization and apheresis in a single patient cohort, following administration 
of single and 2 consecutive-day doses of MGTA-145 and plerixafor, respectively. 
Part A and Cohort Review Committee assessment: Part A has a planned enrollment of 
approximately 7 to 11 evaluable subjects. The first cohort of 4 subjects is to receive a single 
g MGTA-145 is to be administered via a 3 to 10-minute IV infusion, approximately 2 hours after plerixafor SC injection. Instructions 
regarding administration are provided in the Study Pharmacy Manual. 
h Total nucleated cell count and CD34+ cell count in absolute numbers and per kg. 
i ASCQ-Me® and PROMIS® questionnaires will be completed prior to dosing on Day 1. 
j Collection of non-serious AEs and SAEs will begin once the Informed Consent Form (ICF) has been signed. Any SAE occurring after the 
reporting period must be promptly reported if a causal relationship to study drugs is suspected. 
k End-of-study visit phone call will occur 30 days (±3 days) after the last dose of MGTA-145 was received, to assess adverse events and 
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0.24 mg/kg SC dose of plerixafor followed 2 hours later by a single 0.03 mg/kg IV dose of 
MGTA-145. Apheresis is planned to commence within approximately 30 to 45 minutes of 
dosing. For this initial cohort, only one subject will be dosed and apheresed on a single-day, and 
each subject will complete the 1-week follow-up visit before a subsequent subject can be dosed. 
After the first cohort has completed the 1-week follow-up visit, an independent Data Monitoring 
Committee (DMC), comprising 3 members with medical expertise in the conduct of stem cell 
transplantation in patients with SCD as well as the conduct of clinical trials in general, will 
evaluate the safety, PK, and mobilization kinetics of MGTA-145 before the second cohort may 
be enrolled. The DMC may recommend enrolling an additional 3 subjects at the 0.03 mg/kg 
MGTA-145 dose or an additional 7 subjects at a reduced dose of 0.015 mg/kg MGTA-145 or an 
alternative but lower dosing regimen for this cohort. The MGTA-145 dose will not be escalated 
during either Parts A or B. 
After the second cohort has completed the 1-week follow-up visit, the DMC will likewise 
evaluate the safety, PK, and mobilization kinetics of MGTA-145 before subjects may be enrolled 
into Part B. Criteria for the DMC recommendations regarding cohort progression and dosing 
regimen will be defined in the DMC Charter. 
Part B: Part B has a planned enrollment of approximately 3 evaluable subjects. Subjects will 
receive single doses of MGTA-145 and plerixafor on 2 consecutive days, followed by apheresis 
on each dosing day. The plerixafor and MGTA-145 doses on each of the 2 consecutive days will 
be identical to that of the second Part A cohort, unless otherwise recommended by the DMC. 
All subjects in Parts A and B will be observed at the investigational site from Day -1 until at 
least one day after the last apheresis and attend a 1-week (7 to 10 days) follow-up visit after the 
last MGTA-145 infusion. All subjects will attend an EOS phone visit 30 days after the last 
MGTA-145 infusion. 
For both Parts A and B, peripheral CD34+ cell counts will be performed pre- and post-dosing 
with plerixafor and post-dosing with MGTA-145, up to 5 minutes prior to apheresis (Table 8). 
Hematopoietic stem cells obtained by apheresis (HPC-A) will be processed according to 
standardized clinical cell therapy laboratory procedures. Peripheral blood and HPC-A will be 
stored for testing (e.g., exploratory PD evaluation, cell characterization, and process 
characterization) and by the investigational sites for potential future transplantation. 
6.4. 
Number of Subjects 
Approximately 10 to 14 evaluable subjects with SCD are planned to be enrolled in this two-part 
study. 
• Part A has a planned enrollment of approximately 7 to 11 evaluable subjects. 
• Part B has a planned enrollment of approximately 3 evaluable subjects. 
6.5. 
Treatment Assignment 
This is an open-label study, in which all subjects will receive MGTA-145 and plerixafor as study 
drug. 
All study subjects who are consented (including screen failures) will be assigned a subject 
identification number. The unique subject identification number will consist of 6 digits (xxxyyy). 


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The first 3 digits of the number will represent the study site and the second 3 digits will represent 
the subject at that study site. Any subject identification number that is assigned will not be 
reused even if a subject does not receive study drug. 
6.6. 
Stopping Rules 
6.6.1. 
Scheduled Stopping Rule Assessments 
For the purposes of this study, a vaso-occlusive event (VOE, aka: vaso-occlusive crisis, sickle 
cell pain crisis) is defined as pain and/or injury as a result of ischemia due to vascular obstruction 
by sickled RBCs. Clinical manifestations of VOEs may include episodes of acute pain and/or 
evidence of organ involvement presenting as priapism, acute chest syndrome, splenic 
sequestration, hepatic sequestration, cerebrovascular ischemic event, or dactylitis. 
Patients with SCD are known to commonly experience VOEs during and immediately following 
mobilization and apheresis, with approximately 30% of plerixafor-mobilized patients reported to 
have experienced a ≥Grade 3 VOE during and after apheresis, and approximately 20% of 
patients reported to have experienced serious vaso-occlusive pain within 2 days post- 
procedure.20,22 The stopping rules described below have therefore been designed to be triggered 
if the frequency of Grade 3 VOEs occurring within approximately one week (1-week follow-up 
visit, occurring 7 to 10 days) after MGTA-145 dosing exceeds that which would be expected 
using plerixafor alone, to be evaluated at each scheduled DMC assessment. Pain occurring 
during the infusion or immediately after infusion and resolving within 1 hour of infusion will not 
be considered a VOE and will not count toward the stopping rule. Furthermore, as described 
below in Section 6.6.1.3. (Unscheduled Stopping Rule Assessment), the occurrence of a ≥Grade 
4 VOE in any subject occurring within approximately one week (1-week follow-up visit, 
occurring 7 to 10 days) after MGTA-145 dosing will be considered a stopping rule. 
6.6.1.1. 
Scheduled Part A, First Cohort DMC Stopping Rule Assessment 
Using the probability data presented in Table 9 below, the likelihood of a Grade 3 VOE 
occurring in more than 2 of 4 subjects comprising the first Part A cohort within approximately 
one week would be 8.37%, assuming that the true incidence using plerixafor alone is 30%. 
Therefore, if more than 2 of the 4 subjects in the first Part A cohort report a Grade 3 VOE within 
approximately one week (up until the 1-week follow-up visit), no further dosing will take place 
unless the DMC determines that it is safe to do so. 
Table 9: 
Probabilities of Grade 3 VOEs Occurring in Given Numbers of Study 
Subjects Undergoing Apheresis in the First Patient Cohort of Part A Within 
Approximately One Week, if Mobilized with Plerixafor Alone 
 
Greater Than Grade 
3 VOE 
Probability if 
True=20% 
Probability if 
True=30% 
Probability if 
True=40% 
≥1/4 
59.04% 
75.99% 
87.04% 
≥2/4 
18.08% 
34.83% 
52.48% 
≥3/4 
2.72% 
8.37% 
17.92% 
4 
0.16% 
0.81% 
2.56% 


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6.6.1.2. 
Scheduled Part A, Second Cohort DMC Stopping Rule Assessment: 
Based on the probability data presented in Table 10 below, the likelihood of a Grade 3 VOE 
occurring in more than 3 of 7 subjects completing Part A within approximately one week would 
be 12.60%, assuming that the true incidence using plerixafor alone is 30%. Therefore, if more 
than 3 of 7 patients completing Part A at a specific dosing regimen report a Grade 3 VOE within 
approximately one week (up until the 1-week follow-up visit), the study will not progress to Part 
B dosing unless the DMC determines that it is safe to do so. 
Table 10: 
Probabilities of Grade 3 VOEs Occurring in Given Numbers of Study 
Subjects Undergoing Apheresis in the Second Patient Cohort of Part A 
Within Approximately One Week, if Mobilized with Plerixafor Alone 
 
Probability of > 
Grade 3 VOE 
Probability if 
True=20% 
Probability if 
True=30% 
Probability if 
True=40% 
>1/7 
79.03% 
91.76% 
97.20% 
>2/7 
42.33% 
67.06% 
84.14% 
>3/7 
14.80% 
35.29% 
58.01% 
>4/7 
3.33% 
12.60% 
28.98% 
>5/7 
0.47% 
2.88% 
9.63% 
>6/7 
0.04% 
0.38% 
1.88% 
7 
0.01% 
0.02% 
0.16% 
Furthermore, the DMC may determine that the study should not proceed to the subsequent cohort 
at the current dosing regimen, based on the entirety of data available, regardless of whether a 
cohort stopping rule has been met. 
6.6.1.3. 
Unscheduled Stopping Rule Assessment 
In addition to the cohort stopping rules outlined above, if within approximately one week (up 
until the 1-week follow-up visit) after MGTA-145 dosing, any subject develops a Grade >4 
VOE, or a Grade >3 drug-related TEAE (based on the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0) other than VOE, dosing of the 
current cohort will not be continued until the DMC assesses whether dosing may continue and 
whether dosing modifications are needed. In addition to VOEs, Grade 3 AEs known to be 
associated with plerixafor (i.e., nausea, vomiting, diarrhea, headache [as per plerixafor label]) or 
MGTA-145 (i.e., musculoskeletal pain that is less than 1 hour in duration from the time pain is 
first reported) will not count toward this stopping rule. 
6.7. 
Criteria for Study Stopping/Termination 
The Sponsor (Magenta) may stop/terminate the study due to the following reasons: 
• Emergence of unacceptable safety risk to subjects. 
• Failure of the Investigator or site to adhere to the protocol or regulatory requirements. 


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If the Sponsor decides to stop/terminate the study, the Sponsor will promptly notify the Principal 
Investigator and the relevant regulatory authority. The Principal Investigator will be responsible 
for notification of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Criteria for Inclusion for Parts A and B 
1. Subject must be 18 to 35 years of age, inclusive. 
2. Subject must weigh ≥30 kg at screening. 
3. Subject must have a documented diagnosis of SCD, with documentation of SCD 
genotype by medical history. 
4. Subject must present with a feasible manual or automated exchange transfusion plan to 
achieve Hemoglobin S (HbS) <30% within 1 week of mobilization. 
5. Subject taking hydroxyurea must comply with a washout period of at least 30 days prior 
to mobilization dosing. Subjects must be able to safely discontinue hydroxyurea to 
participate in the study. 
6. Subject must have a local laboratory screening white blood cell (WBC) count >2.0 x 
109/L, absolute neutrophil count (ANC) >1.0 x 109/L, and platelet count >150 x 109/L 
7. Subject must have a local laboratory screening estimated glomerular filtration rate 
(eGFR) of at least 60 mL/min/1.73 m2 based on the CKD-Epi equation. 
8. Subject must have a local laboratory screening alanine aminotransferase (ALT) value 
<2.5 x upper limit of normal (ULN). 
9. Subject’s cardiac and pulmonary status must be sufficient to undergo apheresis, as 
assessed by the Investigator. 
10. Subject must sign an IRB-approved informed consent form (ICF) and be willing to 
comply with the requirements of the protocol. 
7.2. 
Criteria for Exclusion for Parts A and B 
1. Subject with a VOE requiring a visit to a healthcare facility within 30 days of screening. 
2. Subject with onset of clinically apparent cerebrovascular accident (CVA) or retinal 
infarct in the 2 years prior to screening or determined to be at high risk of CVA, based on 
concomitant disease (e.g., moyamoya), or imaging (e.g., trans-cranial doppler study). 
3. Subject with splenomegaly, splenic sequestration, sickle hepatopathy, priapism requiring 
inpatient treatment, acute chest syndrome requiring supplemental oxygen, or 
osteomyelitis within 6 months of screening. Subjects with a history of splenomegaly or 
splenic sequestration may be included if they have undergone a splenectomy. 
4. Subject having surgery requiring greater than local anesthesia within 3 months of 
screening, except for placement of a central venous access device. 
5. Subject who has received or plans to receive anticoagulation at the time of screening, 
except for study-related procedures. 


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6. Subject who, by medical history, requires rare donor registry red blood cell (RBC) units 
for transfusion, or is unable to receive routine transfusion. Eligible study subjects must 
have undergone prior work-up for the presence of red cell alloantibodies and 
confirmation of available compatible blood product support. 
7. Subject who has undergone or attempted and failed previous HSC collection. 
8. Subject who has had a prior autologous or allogeneic transplantation, inclusive of gene 
therapy. 
9. Subject who has received experimental therapy within 4 weeks of providing informed 
consent or is enrolled in another interventional experimental protocol. 
10. Subject with poorly controlled diabetes mellitus, as assessed by the Investigator. 
11. Subject who has an uncontrolled cardiovascular condition, including clinically significant 
cardiac arrhythmia, congestive heart failure, angina, myocardial infarction, or unstable 
pulmonary arterial hypertension within 6 months of screening. 
12. Subject with a history of or who has a positive screening laboratory test for human 
immunodeficiency disease (HIV), hepatitis B, hepatitis C, or human T-cell leukemia 
virus (HTLV). 
13. Subject with active infection or co-morbid condition that places the subject at high risk 
for treatment complications, as assessed by the Investigator. 
14. Subject with a known allergy to or contraindication for MGTA-145, plerixafor 
administration, or medications routinely administered during apheresis. 
15. Male subject not willing or able to use a highly effective method of contraception for 3 
months during and after treatment with MGTA-145 and plerixafor, or female subject who 
is pregnant or breastfeeding, or sexually active and not willing or able to use a highly 
effective method of contraception for 3 months during and after treatment with MGTA- 
145 and plerixafor. 
7.3. 
Subject Withdrawal Criteria 
A subject may be discontinued from the study procedures at the discretion of the Investigator. In 
such a case, the decision to discontinue the subject will be made by the Investigator in 
consultation with the study Medical Monitor. Subjects may voluntarily withdraw consent to 
participate in the study for any reason at any time. Withdrawal of consent occurs when a subject: 
• Does not want to continue participation in the study 
• Does not want any further study visits or assessments 
• Does not want any further study-related contacts 
Subjects who discontinue study procedures should not be considered withdrawn from the study 
unless they withdraw their consent. If a subject withdraws consent, the Investigator must make 
every effort (e.g., telephone, email, letter) to determine the primary reason for this decision and 
record this information in the electronic case report form (eCRF). If the subject is willing to 


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perform end-of-study assessments, these should be conducted. Otherwise, no further assessments 
should be conducted. All biological material that has not been analyzed at the time of withdrawal 
must not be used unless written consent is obtained. Further attempts to contact the subject are 
not allowed unless safety findings require communication or follow-up. 


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8. 
TREATMENT OF SUBJECTS 
8.1. 
Description of Study Drug 
MGTA-145 is a 4 amino acid-truncated protein variant of the CXCR2 agonist CXCL2. 
8.1.1. 
Dose Cohort(s) Planned for Part A 
The initial Part A subject cohort will enroll and complete treatment and 1-week follow-up of 4 
evaluable subjects with SCD, aged 18 to 35 years, who will receive an MGTA-145 dose of 0.03 
mg/kg approximately 2 hours after receiving a plerixafor dose of 0.24 mg/kg. This will be 
followed by a DMC review of the safety, PK, PD, and mobilization kinetics data for the 4 
subjects who have completed their 1-week follow-up visit. 
For the second Part A subject cohort, the DMC may recommend enrolling an additional 3 
subjects at the 0.03 mg/kg MGTA-145 dose or an additional 7 subjects at a reduced dose of 
0.015 mg/kg MGTA-145 or an alternative dosing regimen, as recommended by the DMC. 
8.1.2. 
Dose Cohort Planned for Part B 
Part B has a planned enrollment of approximately 3 evaluable subjects. Subjects with SCD, aged 
18 to 35 years, will receive single doses of MGTA-145 and plerixafor on 2 consecutive days, 
followed by apheresis on each dosing day. The dose of MGTA-145 will be identical to that of the 
second Part A cohort, unless otherwise recommended by the DMC. 
8.2. 
Concomitant Medications and Supportive Care 
Supportive care measures for SCD and its associated complications will be provided in 
accordance with local institutional guidelines. 
Pre-medications will be administered at the discretion of the Principal Investigator according to 
institutional or center standard for apheresis collection. 
A widespread US vaccination campaign against COVID-19 infection is ongoing during the 
conduct of this study. Vaccination against COVID-19 is essential to protect at-risk patient 
populations, including adults with SCD. Consistent with the NMDP/Be The Match 
recommendations, study subjects should receive vaccine when available to them. To distinguish 
possible side effects of vaccine from study participation, subjects should receive vaccine more 
than 72 hours before dosing of study drug and mobilization, if possible. 
Prohibited medications: 
Subjects cannot receive treatment with hydroxyurea during this study. Subjects taking 
hydroxyurea must comply with washout of at least 30 days prior to dosing of study drug. 
Subjects must be able to safely discontinue hydroxyurea to participate in the study, based on the 
clinical judgment of the Investigator. 
Concomitant treatment with investigational agents is not allowed during the study. 
8.3. 
Treatment Compliance 
Administration of MGTA-145 and plerixafor will be performed under the supervision of the 
Investigator (or designee). Drug accountability procedures will be used to assess treatment 


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compliance. Compliance with study drug is defined as the subject receiving 100% of the planned 
dosage. Drug administration will be recorded and any discrepancies with the dosing regimen 
must be explained in the eCRF. 
8.4. 
Randomization and Blinding 
This study is an open-label study; therefore, study personnel and study subjects will not be 
blinded to the treatment administered/received. 


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9. 
STUDY DRUG MATERIALS AND MANAGEMENT 
9.1. 
Study Drug 
MGTA-145 is formulated in 
 
. 
MGTA-145 injection is provided as a sterile solution for intravenous infusion in 2 mL Type I 
amber glass vials. Each vial contains 1 mL of a 20 mg/mL solution. Up to two daily 0.03 mg/kg 
doses of MGTA-145 will be administered as a single 3- to 10-minute IV infusion approximately 
2 hours after 0.24 mg/kg SC administration of plerixafor. 
Plerixafor (injection) is provided as a sterile, preservative-free, clear, colorless to pale yellow, 
isotonic solution for SC injection. Each mL of the sterile solution contains 20 mg of plerixafor. 
Each single-use vial is filled to deliver 1.2 mL of the sterile solution that contains 24 mg of 
plerixafor and 5.9 mg of sodium chloride in Water for Injection adjusted to a pH of 6.0 to 7.5 
with hydrochloric acid and with sodium hydroxide, if required. 
Study drug characteristics are summarized in Table 11 below. 
Table 11: 
Study Drug 
 
Product Name: 
MGTA-145 
Plerixafor 
Dosage Form: 
Injection 
Injection 
Unit Dose: 
Single dose 2 mL Type I amber glass 
vial 
Single dose vial 
Route of 
Administration: 
IV 
SC 
Physical Description: 
Clear, colorless solution, essentially 
free of visible particles 
Clear, colorless to pale yellow, 
isotonic solution 
9.2. 
Study Drug Packaging and Labeling 
MGTA-145 is supplied in a single dose 2 mL Type I amber glass vials and packaged in cartons. 
Each vial and carton will be labeled in accordance with regulatory/study requirements. 
Commercially available plerixafor will be supplied by the study site in the commercially 
approved packaging and labeling. 
9.3. 
Study Drug Storage and Stability 
MGTA-145 vials should be stored at -20°C ±5°C in the carton to protect from light. 
Plerixafor should be stored according to the manufacturer’s instructions. 


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9.4. 
Study Drug Preparation 
A vial of MGTA-145 should be thawed according to the Study Pharmacy Manual prior to use; 
MGTA-145 vials are stable at 2°C to 8°C for up to 30 days. Once thawed, MGTA-145 should 
not be refrozen. 
Plerixafor is supplied as a ready-to-use formulation. 
9.5. 
MGTA-145 and Plerixafor Administration 
MGTA-145 should be diluted in 0.9% saline in accordance with the Study Pharmacy Manual. 
Dosing solutions of MGTA-145 prepared in 0.9% saline may be stored for no more than 8 hours 
at room temperature prior to administration. MGTA-145 is to be administered via a 3- to 10- 
minute IV infusion, approximately 2 hours after plerixafor SC injection. Instructions regarding 
administration are provided in the Study Pharmacy Manual. 
Plerixafor is to be administered SC per the manufacturer’s instructions. 
9.6. 
Study Drug Accountability 
The Investigator will ensure that the study drug is used only in accordance with this protocol. 
The Investigator or designee is responsible for recording the details of the IV administration of 
MGTA-145 on the subject’s eCRF. 
9.7. 
Study Drug Handling and Disposal 
Periodically, and/or after completion of the study, all used study drug containers (including 
empty containers) of MGTA-145 must be reconciled and destroyed at the site per the Study 
Pharmacy Manual. If the site does not have appropriate procedures in place for destroying used 
study drug, used study drug should be returned to Magenta (or designee) for destruction. Study 
drug cannot be used for any other purpose than that described in this protocol. 


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10. 
PHARMACOKINETIC, PHARMACODYNAMIC, AND 
IMMUNOLOGIC ASSESSMENTS 
10.1. 
Pharmacokinetic Assessments 
Samples for MGTA-145 PK determinations will be collected for all subjects enrolled in Parts A 
and B at the timepoints outlined in the section below and the Schedule of Assessments. 
As specified in Table 8, a plasma sample will be collected within 15 minutes prior to MGTA-145 
dosing and at 2 time points, spaced at least 15 minutes apart, prior to the initiation of apheresis. 
If apheresis is not initiated within 45 minutes of MGTA-145 dosing, a third PK sample will be 
drawn within 5 minutes prior initiation of apheresis. 
Details regarding blood sample collection are provided in the Laboratory Manual. 
10.2. 
Pharmacodynamic Assessments 
Changes in cell functionality will be assessed in terms of colony-forming units (CFUs) using an 
automated colony-counting device (StemVision™ from Stemcell Technologies) or manually 
with an inverted microscope. 
10.2.1. 
Colony-Forming Unit Analysis 
For all subjects enrolled in Parts A and B, whole blood will be collected as outlined in the 
Schedules of Event (Table 6 for Part A and Table 7 for Part B) to analyze changes in 
granulocyte-macrophage colony-forming units (CFU-GMs), granulocyte-erythrocyte- 
macrophage-megakaryocyte colony-forming units (CFU-GEMMs), and erythroid burst-forming 
units (BFU-Es). Briefly, blood samples will be plated in specially formulated methylcellulose 
media and cultured for 7 to 10 days at 37˚C with 5% CO2. The number of CFUs in each sample 
will be assessed with an automated colony-counting device (StemVision™ from Stemcell 
Technologies) or manually with an inverted microscope. 
Details regarding this collection will be provided in the Laboratory Manual. 
10.2.2. 
Apheresis Yield 
Apheresis cell collection as outlined in the Schedule of Events (Table 6 for Part A and Table 7 
for Part B) from all subjects enrolled in Parts A and B will proceed according to standardized 
procedures and start within an hour after MGTA-145 infusion. All subjects will undergo 
apheresis collection according to institutional practice, not to exceed a total of 8 hours. Apheresis 
yield will be measured as the total nucleated cell count and CD34+ cell count in absolute 
numbers and per kilogram. These determinations will be performed using fluorescent flow 
cytometry. 
10.2.2.1. Peripheral Blood CD34+ Counts 
For all subjects enrolled in Parts A and B, whole blood samples for determination of peripheral 
CD34+ cell counts will be collected at the timepoints specified in Table 8. Details regarding 
peripheral CD34+ cell blood sample collection during Parts A and B are provided in the 
Laboratory Manual. Determination of changes in CD34+ and CD34+CD90+CDRA- cell counts, as 


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well as T-cell subtypes, B cells, monocytes, granulocytes, and natural killer (NK) cells will be 
performed using fluorescent flow cytometry. 
Changes in cell functionality will be assessed in terms of CFUs using an automated colony- 
counting device (StemVision™ from Stemcell Technologies) or manually with an inverted 
microscope. 
10.2.2.2. Exploratory Graft Characterization 
For all subjects enrolled in Parts A and B, HPC-A will be collected as outlined in Table 8 to 
assess graft immunophenotype, function, and ability to select and gene-modify CD34+ cells. 
Details regarding this collection will be provided in the Laboratory Manual. 
10.3. 
Immunologic Assessments 
Plasma samples for measurement of anti-drug antibodies will be collected as outlined in Table 8. 
Screening for anti-drug antibodies in plasma will be conducted using a bridging immunogenicity 
assay (electrochemiluminescent immunoassay [ECLIA]). In the initial screen, test samples will 
be evaluated based on an assay cut point determined by 10+ individual lots of naïve plasma per 
plate. Samples that test positive will then be re-tested in a confirmatory competitive binding 
assay where free drug is spiked into the reaction at a 50:1 excess. 
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the Laboratory Manual. 


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11. 
ASSESSMENT OF SAFETY 
Subject safety will be assessed based on monitoring of AEs, vital signs, physical examinations, 
clinical laboratory evaluations, and development of anti-drug antibodies. Adverse events will be 
graded using the NCI CTCAE version 5.0. 
Vaso-occlusive events are known to be associated with plerixafor use in patients with SCD 
undergoing mobilization and apheresis, reaching Grade 3 or higher severity in approximately 
30% of patients.20,22 During each planned post-cohort assessment, the DMC is to evaluate and 
recommend whether to proceed to the subsequent cohort at the current dosing regimen based on 
evaluation of safety, PK, and mobilization kinetics. At each assessment, the number and 
proportion of patients reporting VOEs within approximately one week (1-week follow-up visit, 
occurring 7 to 10 days) after MGTA-145 dosing will be determined, and the DMC will 
determine whether a stopping rule has been met (Section 6.6), in which case no further dosing at 
that dosing regimen will take place unless the DMC determines that it is safe to do so. Pain 
occurring during the infusion or immediately after infusion and resolving within 1 hour of 
infusion will not be considered VOE and will not count toward the stopping rule. 
In Part B, if a subject has a VOE following the first MGTA-145 infusion, proceeding to the 
second infusion will be at the Investigator’s discretion. 
As described below in Section 6.6, the occurrence of a Grade >4 VOE in any subject within 
approximately one week (1-week follow-up visit, occurring 7 to 10 days) after MGTA-145 
dosing will be considered a stopping rule. 
Excluding VOE, if any subject develops a Grade 3 or higher drug-related TEAE, based on the 
NCI CTCAE version 5.0, dosing of the current cohort will not be continued until the DMC 
assesses whether dosing may continue and whether dosing modifications are needed. In addition 
to VOEs, Grade 3 AEs known to be associated with plerixafor (i.e., nausea, vomiting, diarrhea, 
headache [as per plerixafor label]) or MGTA-145 (i.e., bone pain that is less than 1 hour in 
duration from the time the bone pain is first reported) will not count toward this stopping rule. 
Pre-medications will be at the discretion of the Principal Investigator according to institutional or 
center standard for apheresis collection. All subjects will have adequate hydration before and 
during the apheresis procedure. 
Subjects will undergo a transfusion regimen (exchange or simple, as available or needed) 
targeting hemoglobin (Hb) 10 g/dL (not to exceed 12 g/dL) prior to mobilization and HbS 
proportion in the blood of <30%; the last exchange transfusion must occur within 7 days of start 
of mobilization. 
11.1. 
Safety Parameters 
11.1.1. 
Demographic Information 
Subject demographic and baseline characteristic data to be collected on all subjects at the 
screening visit include date of birth, age, sex, race, and predominant ethnicity. 


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11.1.2. 
Medical History 
Relevant medical history, including SCD genotype, and current medical conditions will be 
recorded for all subjects at the screening and baseline visits, and will include all prior therapies 
for the treatment of SCD. 
11.1.3. 
Vital Signs 
Vital sign measurements will be obtained at the time points specified in the Schedule of 
Assessments (Table 6 for Part A and Table 7 for Part B) and include body temperature, systolic 
and diastolic blood pressure, pulse rate, respiratory rate, and pulse oximetry. All vital sign 
measurements will be taken in the sitting position after the subject has been resting for 
5 minutes. Vital signs should be taken before any blood samples are drawn. 
11.1.4. 
Weight and Height 
For all subjects enrolled in Parts A and B, weight (kg) will be documented at the baseline (Day - 
1) and the 1-week follow-up visit (Day 7 to 10). Subject height (cm) will be measured at the 
baseline visit. 
11.1.5. 
Physical Examination (Complete and Symptom-directed) 
A complete physical examination will be performed for all subjects at screening, baseline (Day - 
1), and 1-week follow-up visit (Day 7 to 10), for all subjects enrolled in Parts A and B. Complete 
physical examinations will include general appearance, skin, neck (including thyroid), eyes, ears, 
nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular, and nervous 
system, and will be conducted at the screening visit. Information for each physical examination 
must be included in the source documentation at the study site and will be recorded on the eCRF. 
A pretreatment directed physical examination will be performed on treatment Day 1 of Part A 
and on treatment Days 1 and 2 of Part B. All directed physical examinations will be 
symptom-based. 
Any physical examination abnormality deemed clinically significant by the Investigator during 
screening will be reported as medical history. Any physical examination abnormality that 
emerges or has worsened after signing the ICF assessed as clinically significant by the 
Investigator will be reported as an AE. 
11.1.6. 
Electrocardiogram 
A single recording baseline 12-lead electrocardiogram (ECG) will be obtained for all subjects at 
screening. Subjects having any clinically significant ECG abnormality, as assessed by the 
Investigator, will not be allowed to continue in the study. 
11.1.7. 
Clinical Laboratory Assessments 
When a laboratory assessment that is listed in the inclusion/exclusion criteria is outside of a 
protocol-specified range at screening, the assessment may be repeated once prior to study 
number assignment. If the repeat value remains outside of protocol-specified ranges, the subject 
will be excluded from the study. 


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Clinically relevant deviations from the normal range for laboratory test results should be 
evaluated for criteria defining an AE and reported as such. 
Sample collection and handling information for all laboratory evaluations are provided in the 
Laboratory Reference Manual. 
11.1.7.1. Hematology 
Hematology assessments will include complete blood count (CBC), including platelet count and 
leukocyte differential, which will be performed as outlined in the Schedule of Assessments 
(Table 6 for Part A and Table 7 for Part B). 
11.1.7.2. Clinical Chemistry 
Clinical chemistry evaluations will include sodium, potassium, chloride, bicarbonate, blood urea 
nitrogen, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, albumin, total and 
indirect bilirubin, and will be measured per the Schedule of Assessments (Table 6 for Part A and 
Table 7 for Part B). Clinical chemistry assessments will be done on the morning of the 
assessment day. 
11.1.7.3. Urinalysis 
Per the Schedule of Assessments (Table 6 for Part A and Table 7 for Part B), urinalysis, 
conducted by dipstick, will assess pH, protein, glucose, ketone, urobilinogen, bilirubin, blood, 
specific gravity, nitrite, and leukocytes. 
11.1.7.4. Virus Serology 
All study subjects enrolled in Parts A and B will be screened for HIV, hepatitis B surface antigen 
(HbsAg), HTLV, and HCV at the screening visit. Subjects who are HCV-antibody positive must 
have a negative HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) test in order to 
be considered eligible for study participation. 
11.1.7.5. Pregnancy Screen 
All females of childbearing potential enrolled in Parts A and B will have a serum or urine beta- 
human chorionic gonadotropin (β-hCG) pregnancy test performed at the screening visit and at 
baseline (Day -1). 
11.1.8. 
Patient Surveys 
Patient Survey forms used in the study as outlined in the Schedule of Assessments (Table 6 for 
Part A and Table 7 for Part B) are provided in Appendix Section 18.2. 
11.1.8.1. ASCQ-ME® 
The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®) is a 
patient-reported outcome measurement system that evaluates the physical, mental, and social 
well-being of adults with SCD across 5 domains, including emotional impact, social functioning, 
pain, stiffness, and sleep functioning. 


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For all subjects enrolled in Parts A and B, the ASCQ-Me® will be performed prior to dosing on 
Day 1 and at the 1-week follow-up visit (Day 7-10). 
11.1.8.2. PROMIS® 
The Patient-Reported Outcomes Measurement Information System (PROMIS®) evaluates 
the physical, mental, and social well-being of adults and children living with chronic conditions. 
Among the 7 primary PROMIS domains (physical function, anxiety, depression, fatigue, sleep 
disturbance, ability to participate in social roles and activities, and pain interference), only the 
pain intensity and pain interference domains are to be performed in this study, prior to dosing on 
Day 1 and at the 1-week follow-up visit (Day 7 to 10). 
11.1.9. 
EOS Phone Visit 
End-of-study phone visit will occur 30 days (±3 days) after the last dose of MGTA-145 was 
received, to assess adverse events and concomitant medications. 
11.2. 
Adverse Events and Serious Adverse Events 
11.2.1. 
Adverse Events 
Collection of non-serious AEs and serious adverse events (SAEs) will begin once the ICF is 
signed and continue until the EOS visit. Non-serious AEs and SAE reporting will end at the EOS 
visit. Any SAE occurring after the reporting period must be promptly reported if a causal 
relationship to study drugs is suspected. 
11.2.2. 
Adverse Event Definition 
An AE is any untoward medical occurrence (i.e., any unfavorable and unintended sign [including 
abnormal laboratory findings], symptom, or disease) in a subject or clinical investigation subject 
administered a medicinal product. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product. 
The occurrence of AEs should be sought by non-directive questioning of the subject at each visit 
during the study. Adverse events also may be detected when they are suspected by the subject or 
subject’s family during or between visits or through physical examination, laboratory test, or 
other assessments. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• Induce clinical signs or symptoms 
• Are considered clinically significant 
• Require therapy or medical intervention 
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline values or the previous visit, or values which are considered to be non-typical in subjects 
with underlying disease. Investigators have the responsibility for managing the safety of 
individual subjects and identifying and documenting AEs. 


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From the signing of informed consent, non-serious AEs and SAEs must be recorded on the AE 
eCRF for subjects who enroll in the study. The Investigator should attempt to establish a 
diagnosis of the event based on signs, symptoms and/or other clinical information. In such cases, 
the diagnosis should be documented as the AE and/or SAE rather than as the individual 
signs/symptoms. The AEs should be accompanied by the following information: 
1. The CTCAE Grade (version 5.0) 
If CTCAE grading does not exist for an AE (and this is rare), use: 
Grade 1=mild 
Grade 2=moderate 
Grade 3=severe 
Grade 4=life-threatening 
Grade 5- death 
2. Relationship to the study treatments (definitely related, probably related, possibly related, 
unlikely related, not related). 
3. Duration (start and end dates) or if the event is ongoing an outcome of not recovered/not 
resolved should be reported. 
4. Whether it constitutes an SAE (see Section 11.2.4 for the definition of SAE). 
5. Action taken regarding study treatments. 
6. Outcome (not recovered/not resolved; recovered/resolved; recovered/resolved with sequelae; 
fatal; or unknown). Death is an outcome of an event. The event that resulted in death must be 
recorded on the appropriate eCRF and reported as an SAE. 
Treatment related AEs and all SAEs should be followed until resolution, stabilization, or until it 
is judged to be permanent, and an assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the study drug, the 
interventions required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator’s Brochure (IB) or will be communicated between IB updates in the 
form of Investigator Notifications. Information regarding common side effects of plerixafor can 
be found in the product’s package insert. This information will be included in the subject’s 
informed consent and should be discussed with the subject during the study as needed. 
11.2.3. 
Adverse Event of Interest 
Musculoskeletal pain occurring up to 24 hours post administration of MGTA-145, regardless of 
severity or relationship to study drug, will be captured as an AE of interest. The severity (based 
on CTCAE version 5.0), time of onset, duration of back pain, relationship to study drug, 
outcome, action taken regarding study drug, and any treatment administered will be captured in 
the electronic data capture (EDC) system. 


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11.2.4. 
Serious Adverse Event 
A SAE is defined as any appearance of or worsening of any pre-existing undesirable sign(s), 
symptom(s), or medical conditions(s), which meets any one of the following criteria: 
• Is fatal 
• Is life-threatening 
• Results in persistent or significant disability/incapacity 
• Constitutes a congenital anomaly/birth defect 
• Requires inpatient hospitalization or prolongation of existing hospitalization, except: 
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since the start of study drug 
o Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of an SAE given above and not resulting in hospital admission 
o Social reasons and respite care in the absence of any deterioration in the subject’s 
general condition 
• Is medically significant (i.e., defined as an event that jeopardizes the subject or may 
require medical or surgical intervention) 
Life-threatening in the context of an SAE refers to a reaction in which the subject was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if more severe. 
Any suspected transmission of an infectious agent via a medicinal product is also considered an 
SAE. 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the subject or might 
require intervention to prevent one of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias, or convulsions that do not result in hospitalization. 
Serious adverse events are to be monitored continuously and have special reporting requirements 
(see Section 11.5). All SAEs will be followed until resolution, stabilization, or until it is judged 
to be permanent. 
11.3. 
Relationship to Study Drug 
An Investigator who is qualified in medicine must make the determination of relationship to the 
investigational product for each AE/SAE (related or unrelated). The Investigator should decide 


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Premier SAE Reporting Contact Details 
Email: 
 
Fax: 
 
whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the investigational product. If no valid reason exists for suggesting a relationship, 
then the AE/SAE should be classified as “unrelated.” If there is any valid reason, even if 
undetermined, for suspecting a possible cause-and-effect relationship between the investigational 
product and the occurrence of the AE/SAE, then the AE/SAE should be considered “related.” 
For the purpose of regulatory reporting requirements, causal relationships of definite, probable, 
and possible will be considered treatment related, while unlikely and not related will be 
considered not treatment related. 
11.4. 
Recording Adverse Events 
In the event that a subject experiences an AE or SAE, an assessment of the event will be 
performed at the study site at the time of the incident and recorded on the AE eCRF page. If the 
subject is not evaluated at the study site at the time of the AE/ SAE, every effort will be made to 
obtain safety assessment data from the subject’s local treating physician. If a subject is 
prematurely discontinued from study procedures, only safety data considered relevant for the 
assessment of the MGTA-145 safety profile will be collected in the clinical database. 
11.5. 
Reporting Serious Adverse Events 
To ensure subject safety, every SAE occurring after the subject has provided informed consent, 
through the end of the study, regardless of causality, must be reported to Premier within 24 hours 
of learning of its occurrence. Drug-related SAEs reported to the study site after the EOS visit 
should also be reported to Premier. 
Recurrent episodes, complications, or progression of the initial SAE must be reported as follow- 
up to the original episode, regardless of when the event occurs. This report must be submitted 
within 24 hours of the Investigator receiving the follow-up information. An SAE that is 
considered completely unrelated to a previously reported one should be reported separately as a 
new event. 
In addition, SAEs (initial and follow-up) must be reported to Premier within 24 hours of 
awareness of the SAE or changes to an existing SAE. This should be done by emailing or faxing 
a signed copy of the SAE Report Form using the contact details below. 
 
Follow-up information provided should describe whether the event has resolved or continues, if 
and how it was treated, and whether the subject continued or withdrew from study participation. 
If the SAE is not previously documented in the IB and is thought to be related to the 
investigational treatment, Magenta may urgently require further information from the 
Investigator for regulatory authority reporting. Magenta may need to issue an Investigator 
Notification to inform all Investigators involved in any study with the same investigational 


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treatment that this SAE has been reported. Each site is responsible for notifying their IRB/IEC of 
these SAEs in accordance with local regulations. Suspected unexpected serious adverse reactions 
(SUSARs) will be collected and reported to the regulatory authorities and relevant IRBs in 
accordance with local laws and regulations. It is the responsibility of the Investigator to notify 
the IRB of SAEs that occur at his or her site per IRB reporting requirements. 
11.6. 
Overdose 
For this study, overdose is defined as a dose of study medication higher than the prescribed dose. 
In the case of overdose, the Investigator should be notified immediately, and supportive care 
given as indicated. Overdose will not be considered an SAE unless the overdose meets serious 
criteria as defined in Section 11.2.4. In the event of an overdose, the Magenta Medical Monitor 
should be notified within 24 hours. The subject should be carefully monitored for potential 
adverse reactions and symptomatic treatment instituted as per standard of care. 
11.7. 
Reporting Pregnancy 
Every pregnancy occurring up to 3 months after the last dose of study drug in subjects or 
partners of male subjects after the subject was administered MGTA-145, must be reported to 
Premier within 24 hours of learning of its occurrence. The pregnancy should be followed to 
determine outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. A pregnancy occurring after signing the ICF and before the subject is enrolled 
will preclude study participation. 
Pregnancy should be recorded on a Premier Pregnancy Data Collection Report Form and be 
reported by the Investigator to Premier using the contact information provided in Section 11.5. 
Pregnancy follow-up should be recorded on the same form and should include an assessment of 
the possible relationship to the study drugs of any pregnancy outcome. Any SAE experienced 
during pregnancy must be reported on the SAE Report Form. 
If the father received study drug, consent to report information regarding pregnancy outcome 
needs to be obtained from the mother. 


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12. 
STATISTICS 
A formal statistical analysis plan (SAP) will be developed that includes a detailed description of 
all planned analyses, pre specified exploratory analyses, and any data handling conventions. 
12.1. 
Analysis Sets 
Evaluable Analysis Sets: The evaluable analysis set for Part A will include all subjects that have 
received MGTA-145 and plerixafor and undergone successful apheresis collection. The 
evaluable analysis set for Part B will include all subjects that have received 2 consecutive doses 
of MGTA-145 and plerixafor, and successfully completed at least 1 of the 2 apheresis sessions. 
The Safety Analysis Set: The safety analysis set will consist of all subjects who are enrolled and 
received a dose of MGTA-145. Subjects in this analysis set will be used for demographic, 
baseline characteristics, and safety summaries. 
Pharmacokinetics Analysis Set: The PK analysis set will include all subjects with available 
MGTA-145 PK data and no major protocol deviations with relevant impact on PK data. 
Pharmacodynamics Analysis Set: The PD analysis set will include all subjects with available PD 
data and no major protocol deviations with relevant impact on PD data. 
In general, data will be presented for Parts A and B of the study separately. 
12.2. 
Subject Demographic and Other Baseline Characteristics 
All data for baseline and demographic variables will be listed by subject. Descriptive summary 
statistics will be provided. 
Relevant medical history, current medical conditions, results of laboratory screens, drug tests, 
and any other relevant information will be listed by subject. 
12.3. 
Exposure and Concomitant Medications 
MGTA-145 and plerixafor administrations (time of infusion, duration of infusion, and dose) will 
be summarized. 
Concomitant treatments will be listed and summarized. 
12.4. 
Analysis of the Primary, Secondary, and Exploratory Endpoints 
The endpoints for this study are provided in Section 5.1 and Section 5.2. 
12.4.1. 
Statistical Methods and Analyses 
Statistical summaries will be descriptive in nature. All continuous variables will be summarized 
by dose and visit (as applicable) using descriptive statistics (number of observations [n], mean, 
median, standard deviation [SD], minimum, and maximum). All categorical variables will be 
summarized by dose and visit using frequency counts and percentages. Estimated median, 25th 
and 75th percentiles and standard error of the mean (SEM) from Kaplan-Meier summaries will be 
presented for all time-to-event variables. Subjects will be grouped by dose in all analyses and 
results will be presented by Study Part where applicable. Any subject who receives MGTA-145 
will be included in the analyses. No formal hypothesis testing will be performed. 


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12.4.2. 
Safety 
Safety analyses will include summaries of AEs and SAEs. The number and percentage of 
subjects reporting any TEAEs will be summarized. Adverse events will be tabulated by system 
organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory 
Activities (MedDRA) and relationship to treatment. AEs leading to study drug discontinuation 
and SAEs will be listed. Data listing will be provided for all AEs, TEAEs and SAEs. 
Changes in vital signs and clinical laboratory parameters will be assessed from baseline. 
12.4.3. 
Pharmacokinetics 
Plasma concentrations of MGTA-145 will be listed and a summary by time point for each dose 
cohort will be presented using descriptive statistics (n, mean, SD, median, and range). 
12.4.4. 
Pharmacodynamics 
Peripheral blood will be collected at the timepoints specified in the Schedule of Assessments to 
measure changes in CD34+ and CD34+CD90+CDRA- cell counts, as well as various T-cell 
subtypes, B cells, monocytes, granulocytes, and NK cells. Cell counts will be analyzed using 
fluorescent flow cytometry. 
Changes in cell functionality will be assessed in terms of CFUs using an automated colony- 
counting device (StemVision™ from Stemcell Technologies) or manually with an inverted 
microscope. 
12.5. 
Sample Size Calculation 
There are no statistical hypotheses in this trial, therefore there is no sample size calculation. To 
address the objectives assessing proof of concept of mobilizing CD34+ cells after 1 or 2 days of 
dosing with MGTA-145 and plerixafor, a minimum sample size of 10 evaluable subjects is 
considered adequate. 
Based on the safety profile including 79 subjects dosed with MGTA-145 in Phase 1 study 145- 
HV-101, 10 evaluable subjects are deemed a minimal number to assess common drug-related 
safety events. 
The AE that is clearly related to MGTA-145 infusion is transient, Grade 1 back pain, which was 
observed in a majority of volunteers in the Phase 1 study 145-HV-101. With 10 evaluable 
subjects, there is sufficient subject exposure to assess for this AE. 
Subjects enrolled in the study who are discontinued prior to receiving study drug may be 
replaced. 
Additional subject(s) may be enrolled, if necessary, to ensure minimum numbers of evaluable 
subjects (i.e., subjects without any major protocol deviations affecting the primary endpoint). For 
the primary endpoint in Part A, 7 evaluable subjects are required; the first and second DMC 
assessments require 4 and 7 evaluable subjects, respectively. For the primary endpoint in Part B, 
3 evaluable subjects are required. 


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13. 
DATA REVIEW AND DATABASE MANAGEMENT 
13.1. 
Study Site Monitoring 
Before an investigational site can enter a subject into the study, a representative of Magenta will: 
• Determine the adequacy of the facilities. 
• Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of Magenta or its representatives. This will be 
documented in a Clinical Study Agreement between Magenta and the Investigator. 
During the study, a monitor from Magenta or representative will have regular contacts with the 
investigational site, for the following: 
• Provide information and support to the Investigator(s). 
• Confirm that facilities remain acceptable. 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks 
are being performed. 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the subject’s medical records, and other records relevant to the study. This will 
require access to all original records for each subject (e.g., clinic charts). 
• Record and report any protocol deviations not previously sent to Magenta. 
• Confirm that AEs and SAEs have been properly documented on eCRFs and confirm any 
SAEs have been forwarded to Magenta and those SAEs that met criteria for reporting 
have been forwarded to the IRB. 
The monitor will be available between visits if the Investigator(s) or other staff need 
information or advice. 
13.2. 
Data Collection 
Designated Investigator staff will enter the data required by the protocol into the eCRFs using 
fully validated software that conforms to 21 Code of Federal Regulations (CFR) Part 11 
requirements. Designated Investigator site staff will not be given access to the EDC system until 
they have been trained. Automatic validation programs will check for data discrepancies and, by 
generating appropriate error messages, allow the data to be confirmed or corrected before 
transfer of the data to Magenta. The Investigator must certify that the data entered into the 
eCRFs are complete and accurate. After database lock, the Investigator will receive any of the 
following: a compact disc read-only memory (CD-ROM), paper copies, or a password protected 
universal serial bus (USB) drive of the subject data for archiving at the investigational site. 
Data not requiring a separate written record will be defined in the Data Management Reference 
Manual and Assessment Schedule and can be recorded directly on the eCRFs. All other data 
captured for this study will have an external originating source (either written or electronic) with 
the eCRF not being considered as source. 


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13.3. 
Database Management and Quality Control 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
Magenta or designee will review the data entered into the eCRFs by investigational staff for 
completeness and accuracy and will instruct the site personnel to make any required corrections 
or additions. Queries will be sent to the investigational site using an electronic data query. 
Designated investigational site staff will be required to respond to each query and confirm or 
correct the data. 
Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic 
Chemical classification system. Medical history/current medical conditions and AEs will be 
coded using MedDRA terminology. 
The occurrence of any protocol deviations will be determined. 
After these actions have been completed and the database has been declared to be complete and 
accurate, it will be locked, and the treatment codes will be made available for data analysis. 
13.4. 
Audits and Inspections 
Authorized representatives of Magenta, a regulatory authority, an IEC, or an IRB may perform 
on-site or remote audits or inspections, including source data verification. The purpose of a 
Magenta audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, Good Clinical Practice 
(GCP) guidelines of the International Council for Harmonisation (ICH), and any applicable 
regulatory requirements. The Investigator should contact Magenta immediately if contacted by a 
regulatory agency about an inspection. 
13.5. 
Monitoring Committees 
A DMC, comprising 3 physicians with medical expertise in stem cell transplantation for patients 
with SCD, will evaluate the safety, PK, and mobilization kinetics of MGTA-145 after each of the 
2 patient cohorts completes Part A of the study, and in the event that a stopping rule has been 
met, to assess whether dosing may continue and whether dosing modifications are needed. 


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14. 
ETHICS 
14.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved, or given a 
favorable opinion in writing by an IRB or IEC as appropriate. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit subjects for the study. The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB or IEC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product. Magenta will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
14.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements, 
and Magenta’s policy on Bioethics. 
14.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the subject is given full and adequate 
oral and written information about the nature, purpose, and possible risks and benefits of the 
study. Subjects must also be notified that they are free to discontinue from the study at any time. 
The subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
Patients will be asked to sign an IRB/IEC-approved ICF prior to any study-specific assessments 
in this study. Patient consent/assent is required to give Magenta access to patient data; therefore, 
the patient must sign and date the ICF/assent before an assessment may be collected in the 
Magenta clinical database under this protocol. 


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15. 
DATA HANDLING AND RECORD KEEPING 
15.1. 
Inspection of Records 
Magenta will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 
15.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for Magenta or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 


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16. 
PUBLICATION POLICY 
Magenta assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and finalization 
of the study report, the results of this study will be either submitted for publication and/or posted 
in a publicly accessible database of clinical study results. 


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17. 
LIST OF REFERENCES 
1. Saraf SL, Molokie RE, Nouraie M, et. al. Differences in the clinical and genotypic presentation of 
sickle cell disease around the world. Paediatr Respir Rev 2014; 15(10): 4-12. 
2. Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 
2010;38:S512-21. 
3. Lorey FW, Arnopp J, Cunningham GC. Distribution of hemoglobinopathy variants by ethnicity in 
a multiethnic state. Genet Epidemiol 1996; 13: 501-12. 
4. Lagresle-Peyrou C, Lefrere F, Magrin E, et al. Plerixafor enables safe, rapid, efficient 
mobilization of hematopoietic stem cells in sickle cell disease patients after exchange transfusion. 
Haematologica. 2018;103(5):778-86. 
5. Krishnamurti L. Hematopoietic Cell Transplantation for Sickle Cell Disease. Front Pediatr 2021; 
8(551170): 1-11. 
6. Darbari DS, Brandow AM. Pain-measurement tools in sickle cell disease: where are we now? 
Hematology 2017; 534-41. 
7. Kauf TL, Coates TD, Huazhi L, et al. The cose of health care for children and adults with sickle 
cell disease. Am J Hematol. 2009;84(6):323-7. 
8. Lee S, Vania DK, Bhor M, et al. Patient-Reported Outcomes and Economic Burden of Adults 
with Sickle Cell Disease in the United States: A Systematic Review. Int J Gen Med. 2020;13:361- 
77. 
9. Quinn CT. Clinical severity in sickle cell disease: the challenges of definition and 
prognostication. Experimental biology and medicine 2016; 241: 679-88. 
10. Johnson FL, Look AT, Gockerman J, et al. Bone -marrow transplantation in a patient with sickle- 
cell anemia. N Engl J Med 1984; 311: 780-3. 
11. Rotz SJ, O’Riordan MA, Kim C, et al. Traffic Light: prognosis-based eligibility for clinical trials 
of hematopoietic SCT in adults with sickle cell anemia. Bone Marrow Transplantation. 2015; 50: 
918-23. 
12. Shenoy S. Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and 
opinions. Ther Adv Hematol. 2013;4(5):335-44. 
13. Krishnamurti L. Hematopoietic Cell Trasplantation for Sickle Cell Disease. Front Pediatr. 
2021;8(551170:1-11 
14. Weber L, Poletti V, Magrin E, et al. An Optimized Lentiviral Vector Efficiently Corrects the 
Human Sickle Cell Disease Phenotype. Molecule Therapy: Methods & Clinical Developpment 
2018; 10:268-80. 
15. Prescribing information for Neuopogen (filgrastim) injection. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103353s5184lbl.pdf 
16. Fitzhugh CD, Hseih MM, Bolan CD, et cl. Granulocyte colony-stimulating factor (G-CSF) 
administration in individuals with sickle cell disease: time for a moratorium? Cytotherapy. 
2009;11(4):464-71. 


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17. Prescribing information for Mozobil (Plerixafor). 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022311s001lbl.pdf 
18. Esrick EB, Manis JP, Daley H, et. al. Successful hematopoietic stem cell mobilization and 
apheresis collection using plerixafor alone in sickle cell patients. Blood Adv. 2018 Oct 
9;2(19):2505-2512. 
19. Boulad F, Shore T, vanBesien, et. al. Safety and efficacy of plerixafor dose escalation for the 
mobilization of CD34+ hematopoietic progenitor cells in patients with sickle cell disease: interim 
results. Haematologica. 2018;103(5):770-7. 
20. Uchida N, Leonard A, Stroncek D, et. al. Safe and efficient peripheral blood stem cell collection 
in patients with sickle cell disease using plerixafor. Haematologica. 2020; 105:e497-501. 
21. Hseih MM, Tisdale JF. Hematopoietic stem cell mobilization with plerixafor in sickle cell 
disease. Haematologica. 2018;103(5):749-50. 
22. Tisdale JF, Pierciey FJ, Bonner M, et. al. Safety and feasibility of hematopoietic progenitor stem 
cell collection by mobilization with plerixafor followed by apheresis vs. bone marrow harvest in 
patients with sickle cell disease in the multi-center HGB-206 trial. Am J Hematol. 2020;95(9): 
E239-42. 
23. Sidana S, Bankova A, Hosoya H, et al. Phase 2 study of MGTA-145 + plerixafor for rapid and 
reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple 
myeloma. J Clin Oncol. 2021;39(15S): Abstract 8023. 


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18. 
APPENDICES 
18.1. 
CKD-EPI Equation 
The CKD-EPI equation, expressed as a single equation, is: 
GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] _ 1.159 [if 
black] 
Where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and 
-0.411 for males, min indicates the minimum of Scr/κor 1, and max indicates the maximum of 
Scr/κ or 1. 
18.2. 
Patient Surveys 
18.2.1. 
Adult Sickle Cell Quality of Life Measurement Information®; v2.0 
18.2.1.1. Emotional Impact Domain 
ASCQ-Me Emotional Impact Survey Instructions: Answer all the questions by checking the 
box to the left of your answer. 
1. In the past 7 days, how often did you feel completely hopeless because of your health? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
2. In the past 7 days, how lonely did you feel because of your health problems? 
□ Not at all 
□ A little 
□ Somewhat 
□ Quite 
□ Very 
3. In the past 7 days, how depressed were you about your health problems? 
□ Not at all 
□ A little 
□ Somewhat 
□ Quite 
□ Very 
4. In the past 7 days, how much did you worry about getting sick? 
□ Not at all 
□ A little bit 


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□ Somewhat 
□ Quite a bit 
□ Very much 
5. In the past 7 days, how often were you very worried about needing to go to the hospital? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
18.2.1.2. Pain Impact Domain 
ASCQ-Me Pain Impact Survey Instructions: Answer all the questions by checking the box to 
the left of your answer. 
1. In the past 7 days, how often did you have pain so bad that you could not do 
anything for a whole day? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
2. In the past 7 days, how often did you have pain so bad that you could not get out of 
bed? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
3. In the past 7 days, how often did you have very severe pain? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
4. In the past 7 days, how often did you have pain so bad that you had to stop what you 
were doing? 
□ Never 
□ Rarely 
□ Sometimes 


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□ Often 
□ Always 
5. In the past 7 days, how often did you have pain so bad that it was hard to finish 
what you were doing? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
18.2.1.3. Sleep Impact Domain 
ASCQ-Me Sleep Impact Survey Instructions: Answer all the questions by checking the box to 
the left of your answer. 
1. In the past 7 days, how often did you stay up most of the night because you could 
not fall asleep? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
2. In the past 7 days, how often was it very easy for you to fall asleep? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
3. In the past 7 days, how often did you have a lot of trouble falling asleep? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
4. In the past 7 days, how often did you stay up all night because you could not fall 
asleep? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 


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5. In the past 7 days, how often did you stay up half of the night because you could not 
fall asleep? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
18.2.1.4. Social Functioning Domain 
ASCQ-Me Social Functioning Impact Survey Instructions: Answer all the questions by 
checking the box to the left of your answer. 
1. In the past 30 days, how much did you rely on others to take care of you because of 
your health? 
□ Not at all 
□ A little bit 
□ Somewhat 
□ Quite a bit 
□ Very much 
2. In the past 30 days, how often did your health slow you down? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
3. In the past 30 days, how often did your health make it hard for you to do things? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
4. In the past 30 days, how often did your health keep you from going out? 
□ Never 
□ Rarely 
□ Sometimes 


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□ Often 
□ Always 
5. In the past 30 days, how much did your health make it hard for you to do things 
with your friends? 
□ Not at all 
□ A little bit 
□ Somewhat 
□ Quite a bit 
□ Very much 
18.2.1.5. Stiffness Impact Domain 
ASCQ-Me Stiffness Impact Survey Instructions: Answer all the questions by checking the 
box to the left of your answer. 
1. In the past 7 days, how often were your joints very stiff when you woke up? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
2. In the past 7 days, how often were your joints very stiff during the day? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
3. In the past 7 days, how often were your joints so stiff during the day that you could 
not move? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
4. In the past 7 days, how often did you wake up so stiff that you could not move? 


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□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 
5. In the past 7 days, how often did it take you a very long time to get out of bed 
because of stiffness? 
□ Never 
□ Rarely 
□ Sometimes 
□ Often 
□ Always 


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18.2.2. 
PROMIS®-57 Profile v2.1 (Pain Interference and Pain Intensity Domains)