A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor in Patients With WHIM Syndrome
Phase: PHASE2
Conditions: WHIM Syndrome
Sponsor: X4 Pharmaceuticals

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 1 of 115 
This study will be conducted according to the protocol and in compliance with  
Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki, 
and other applicable regulatory requirements. 
Study Title: 
A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor in 
Patients with WHIM Syndrome 
Investigational Drug: 
Mavorixafor (X4P-001) 
Phase 
2 
IND #: 
129092 
EudraCT# 
2016-005028-26 
ClinicalTrials.gov ID 
NCT03005327 
Sponsor: 
X4 Pharmaceuticals, Inc. 
61 North Beacon Street, 4th Floor 
Boston, MA 02134 
Protocol Number: 
X4P-001-MKKA 
Protocol Version, Date: 
Version 5.0, 21 December 2020 (US & Australia) 
Replaces Version, Date: 
Version 4.6, 10 April 2019 (US & Australia) 
Confidential
Page 1225

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 2 of 115 
INVESTIGATOR STATEMENT 
I understand that all documentation provided to me by X4 Pharmaceuticals, Inc. (X4), or its 
designated representative(s) concerning this study that has not been published previously will 
be kept in the strictest confidence. This documentation includes the study protocol, 
investigator brochure, case report forms, and other scientific data. 
This study will not commence without the prior written approval of a properly constituted 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC). No changes will be 
made to the study protocol without the prior written approval of X4 and the IRB/IEC, except 
where necessary to eliminate an immediate hazard to the patient. 
I have read, understood, and agree to abide by all the conditions and instructions contained in 
this protocol. 
Investigator Signature 
Date 
Printed Name 
Confidential
Page 1226

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 3 of 115 
TABLE OF CONTENTS 
INVESTIGATOR STATEMENT .................................................................................................. 2 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF TABLES IN THE TEXT ................................................................................................. 8 
LIST OF FIGURES IN THE TEXT ............................................................................................... 9 
LIST OF ABBREVIATIONS ....................................................................................................... 10 
1.
PROTOCOL SYNOPSIS ................................................................................................. 12 
SCHEMATIC OF THE STUDY DESIGN................................................................................... 27 
2.
INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC
RATIONALE .................................................................................................................... 28 
2.1. 
Background Information ....................................................................................... 28 
2.1.1. 
Treatment Experience – Plerixafor ...................................................... 32 
2.2. 
Overview of Mavorixafor ..................................................................................... 34 
2.2.1. 
Prior Clinical Studies Conducted Using Mavorixafor ......................... 34 
2.2.2. 
Clinical Pharmacology of Mavorixafor ............................................... 36 
2.2.3. 
Clinical Safety Experience with Mavorixafor...................................... 38 
2.2.4. 
Treatment Effect of Mavorixafor in Prior Clinical Studies ................. 39 
2.2.5. 
Nonclinical Toxicity Studies of Mavorixafor ...................................... 40 
2.3. 
Clinical Experience with Related Compounds ..................................................... 41 
2.4. 
Updated Clinical Experience with Mavorixafor in WHIM Patients ..................... 41 
3.
OBJECTIVES AND PURPOSE ....................................................................................... 44 
3.1. 
Primary Objective ................................................................................................. 44 
4.
STUDY DESIGN AND ENDPOINTS ............................................................................. 45 
4.1. 
Description of the Study Design ........................................................................... 45 
4.2. 
Rationale for the Study Design, Including the Choice of Control Groups ........... 47 
4.2.1. 
Rationale for the ANC and ALC Threshold ........................................ 47 
4.2.2. 
Rationale for the AMC Threshold........................................................ 47 
4.2.3. 
Rationale for Study Structure ............................................................... 48 
4.2.4. 
Rationale for Mavorixafor Dosing Regimen........................................ 48 
4.2.5. 
Rationale for Mavorixafor Duration of Treatment............................... 48 
4.3. 
Endpoints .............................................................................................................. 49 
4.3.1. 
Primary Endpoint ................................................................................. 49 
4.3.2. 
Exploratory Endpoints ......................................................................... 49 
5.
STUDY ENROLLMENT AND WITHDRAWAL .......................................................... 51 
Confidential
Page 1227

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 4 of 115 
5.1. 
Inclusion Criteria .................................................................................................. 51 
5.2. 
Exclusion Criteria ................................................................................................. 51 
5.3. 
Strategies for Recruitment and Retention ............................................................. 52 
5.4. 
Participant Withdrawal or Termination ................................................................ 53 
5.4.1. 
Reasons for Withdrawal or Termination .............................................. 53 
5.4.2. 
Handling of Participant Withdrawals or Termination .......................... 53 
5.5. 
Premature Termination or Suspension of Study ................................................... 53 
5.6. 
Patient Restrictions during the Conduct of the Study ........................................... 54 
5.7. 
Definition of Treatment-Limiting Toxicity .......................................................... 54 
5.8. 
Duration of Treatment........................................................................................... 54 
5.9. 
Number of Patients ............................................................................................... 55 
5.10. Treatment Assignment .......................................................................................... 55 
6. 
STUDY DRUG(S) ............................................................................................................ 56 
6.1. 
Study Drug(s) and Control Description ................................................................ 56 
6.1.1. 
Acquisition ........................................................................................... 56 
6.1.2. 
Formulation, Appearance, Packaging, and Labeling ........................... 56 
6.1.3. 
Product Storage .................................................................................... 56 
6.1.4. 
Preparation ........................................................................................... 56 
6.1.5. 
Dosing and Administration .................................................................. 56 
6.1.6. 
Route of Administration ....................................................................... 57 
6.1.7. 
Starting Dose and Dose Escalation Schedule....................................... 57 
6.1.8. 
Dose Adjustments/Modifications/Delays ............................................ 57 
6.1.9. 
Duration of Therapy ............................................................................. 58 
6.1.10. 
Treatment Compliance ......................................................................... 58 
6.2. 
Study Drug Accountability Procedures ................................................................ 58 
6.3. 
Disposition of Study Drug .................................................................................... 59 
7. 
STUDY PROCEDURES AND SCHEDULE ................................................................... 60 
7.1. 
Study Procedures/Evaluations .............................................................................. 60 
7.1.1. 
Baseline and Safety Assessments ........................................................ 60 
7.1.2. 
Pharmacokinetic Assessments ............................................................. 62 
7.1.3. 
Biomarker Assessments (in PBMC) .................................................... 63 
7.1.4. 
Efficacy Assessments ........................................................................... 63 
7.1.5. 
Assessments of Clinical Benefit........................................................... 64 
7.2. 
Laboratory Procedures/Evaluations ...................................................................... 66 
7.2.1. 
Clinical Laboratory Evaluations .......................................................... 66 
7.2.2. 
Other Assays or Procedures ................................................................. 67 
7.2.3. 
Specimen Preparation, Handling, and Storage ..................................... 67 
7.2.4. 
Specimen Shipment .............................................................................. 67 
7.3. 
Study Schedule...................................................................................................... 67 
Confidential
Page 1228

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 5 of 115 
7.3.1. 
Extension Phase ................................................................................... 68 
7.4. 
Concomitant Medications, Treatments, and Procedures....................................... 69 
7.4.1. 
Precautionary Medications, Treatments, and Procedures .................... 70 
7.4.2. 
Prohibited Medications, Treatments, and Procedures .......................... 71 
7.4.3. 
Prophylactic Medications, Treatments, and Procedures ...................... 72 
7.4.4. 
Rescue Medications, Treatments, and Procedures ............................... 72 
7.4.5. 
Participant Access to Study Drug after Study Completion .................. 73 
7.5. 
Appropriateness of Measurements ........................................................................ 73 
8. 
ADVERSE EVENTS ........................................................................................................ 74 
8.1. 
Definitions............................................................................................................. 74 
8.1.1. 
Adverse Events (AE)............................................................................ 74 
8.1.2. 
Serious Adverse Events........................................................................ 74 
8.1.3. 
Adverse Drug Reaction ........................................................................ 75 
8.1.4. 
Suspected, Unexpected Serious Adverse Reaction .............................. 75 
8.1.5. 
Clinical Laboratory Adverse Events .................................................... 76 
8.2. 
Classification of Adverse Events .......................................................................... 76 
8.2.1. 
Severity ................................................................................................ 76 
8.2.2. 
Grading of Laboratory Safety Tests for Reporting and Analysis ........ 77 
8.2.3. 
Relationship to Study Drug .................................................................. 77 
8.2.4. 
Expectedness ........................................................................................ 78 
8.2.5. 
Date and Time of Onset ....................................................................... 78 
8.2.6. 
Actions Taken for Management of AE ................................................ 78 
8.2.7. 
Follow-up and Outcome of AEs .......................................................... 79 
8.2.8. 
Date and Time of Outcome .................................................................. 79 
8.3. 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 79 
8.4. 
Reporting Procedures ............................................................................................ 80 
8.4.1. 
Adverse Event Reporting ..................................................................... 80 
8.4.2. 
Serious Adverse Event Reporting ........................................................ 80 
8.4.3. 
Events of Special Interest ..................................................................... 81 
8.4.4. 
Reporting of Pregnancy........................................................................ 81 
8.5. 
Study Halting Rules .............................................................................................. 82 
8.6. 
Safety Oversight.................................................................................................... 82 
8.6.1. 
Procedures for Monitoring Risks ......................................................... 82 
8.6.2. 
Data Review Committee ...................................................................... 84 
9. 
CLINICAL MONITORING ............................................................................................. 85 
9.1. 
External Review of the Study Conduct at Participating Sites ............................... 85 
9.2. 
Study Monitoring Visits ........................................................................................ 85 
9.2.1. 
Site Qualification and Initiation Visits ................................................. 85 
9.2.2. 
Interim Monitoring Visits .................................................................... 86 
Confidential
Page 1229

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 6 of 115 
9.2.3. 
Study Closeout Visit ............................................................................ 86 
10. 
STATISTICAL CONSIDERATIONS.............................................................................. 88 
10.1. Statistical and Analytical Plans ............................................................................. 88 
10.2. Statistical Hypotheses ........................................................................................... 88 
10.3. Analysis Datasets .................................................................................................. 88 
10.4. Description of Statistical Methods ........................................................................ 88 
10.4.1. 
General Approach ................................................................................ 88 
10.4.2. 
Analysis of the Primary Efficacy Endpoints ........................................ 89 
10.4.3. 
Analysis of Exploratory Endpoints ...................................................... 90 
10.4.4. 
Safety Analyses .................................................................................... 91 
10.4.5. 
Adherence and Retention Analyses ..................................................... 91 
10.4.6. 
Baseline Descriptive Statistics ............................................................. 91 
10.4.7. 
Planned Interim Analyses .................................................................... 92 
10.4.8. 
Multiple Comparison/Multiplicity ....................................................... 92 
10.4.9. 
Tabulation of Individual Response Data .............................................. 92 
10.5. Sample Size ........................................................................................................... 92 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .......... 93 
11.1. Medical Records ................................................................................................... 93 
11.2. Study-Specific Source Documents ....................................................................... 93 
11.3. Source Documents Requirements ......................................................................... 93 
11.4. Electronic Case Report Forms .............................................................................. 94 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL ................................................ 95 
12.1. Study Monitoring .................................................................................................. 95 
12.2. Case Report Form Completion ............................................................................. 95 
12.3. Computerized Systems / Medical Records as Source Data .................................. 95 
12.4. Audits and Inspections .......................................................................................... 95 
12.5. Resolution of Deficiencies .................................................................................... 95 
13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................ 97 
13.1. Ethical Standard .................................................................................................... 97 
13.2. Institutional Review Board/Independent Ethics Committee................................. 97 
13.3. Informed Consent Process .................................................................................... 97 
13.3.1. 
Consent/Assent and Other Informational Documents Provided to 
Participants ........................................................................................... 97 
13.3.2. 
Consent Procedures and Documentation ............................................. 98 
13.4. Participant and Data Confidentiality ..................................................................... 98 
14. 
DATA HANDLING AND RECORD KEEPING ............................................................ 99 
14.1. Data Collection and Management Responsibilities .............................................. 99 
Confidential
Page 1230

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 7 of 115 
14.2. Study Records Retention....................................................................................... 99 
14.3. Protocol Deviations ............................................................................................... 99 
14.4. Publication and Data Sharing Policy .................................................................... 99 
15. 
STUDY ADMINISTRATION........................................................................................ 101 
16. 
CONFLICT OF INTEREST POLICY............................................................................ 102 
17. 
LITERATURE REFERENCES ...................................................................................... 103 
18. 
APPENDICES ................................................................................................................ 106 
18.1. Revision History and Sponsor Signature ............................................................ 106 
18.2. Quality of Life Assessment (SF-36) ................................................................... 108 
18.3. LIFE QUALITY INDEX .................................................................................... 114 
18.4. Potential P-gp and CYP-Related Drug-Drug Interactions .................................. 115 
 
Confidential
Page 1231

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 8 of 115 
LIST OF TABLES IN THE TEXT 
Table 1-1: 
Schedule of Events –Initial Treatment Period ..........................................................20 
Table 1-2: 
Schedule of Events – Extension Phase .....................................................................23 
Table 1-3 
Estimated Blood Volume - Initial Treatment Period ...............................................25 
Table 1-4: 
Estimated Blood Volume - Extension Phase ............................................................26 
Table 5: 
Reported Clinical Characteristics of Patients with WHIM Syndrome .....................29 
Table 6: 
Estimated Changes in WBC in Patients with WHIM Syndrome during Treatment 
with Plerixafor1 ........................................................................................................33 
Table 7: 
Prior Clinical Studies Conducted Using Mavorixafor – Protocol Number, Study 
Title, and Publication1 ..............................................................................................35 
Table 8: 
Prior Clinical Studies Conducted using Mavorixafor – Study Population, 
Objectives, and Exposures .......................................................................................35 
Table 9: 
Physical and Chemical Properties of Active Ingredient (Drug Substance) .............56 
Table 10: 
Formulation of Mavorixafor 100 mg Capsule ..........................................................56 
Table 11: 
Candidate Subsets of Peripheral Blood Mononuclear Cells for Biomarker Analysis
 ..................................................................................................................................63 
Table 12: 
Common Vaccines That Elicit Protective Antibody by Age Range of Initial 
Administration ..........................................................................................................64 
Table 13: 
Safety Laboratory Tests ...........................................................................................66 
Table 14: 
Dose Modification of Mavorixafor when Co-Administered with a Strong CYP3A4 
Inhibitor ....................................................................................................................71 
Table 15: 
Reporting the Date and Time of Onset of AE for Different Types of Events ..........78 
Table 16: 
Date and Time of Outcome for AE by Outcome Class ............................................79 
Table 17: 
Monitoring Procedures for Risks Identified in Prior Studies of Mavorixafor .........82 
Table 18: 
Definition of Analysis Populations ..........................................................................88 
Table 19: 
Protocol Revision History ......................................................................................106 
 
Confidential
Page 1232

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 9 of 115 
LIST OF FIGURES IN THE TEXT 
Figure 1-1: Dose Titration Strategy and Visit Schedule--Initial Treatment Period ....................27 
Figure 1-2: Overall Study Design--Initial Treatment Period and Extension Phase ....................27 
Figure 3: 
Calculation of 24-hr AUC for a Hypothetical Set of ALC Data ..............................90 
Confidential
Page 1233

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 10 of 115 
LIST OF ABBREVIATIONS 
Abbreviation  
Explanation 
AE 
Adverse event 
AIDS 
Acquired immune deficiency syndrome  
ALC 
Absolute lymphocyte count 
ALT 
Alanine transaminase 
AMC 
Absolute monocyte count 
ANC 
Absolute neutrophil count 
AST 
Aspartate transaminase 
AUC 
Area under the plasma concentration curve 
BID 
Twice daily 
BP 
Blood pressure 
Cmax 
Maximum concentration 
Cmin 
Minimum concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXCL12 
C-X-C motif chemokine ligand 12 
CXCR4 
C-X-C chemokine receptor type 4 
CYP 
Cytochrome P450 
DRC 
Data Review Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
Emax 
Maximum exposure 
EOS 
End-of-Study 
EOT 
End-of-Treatment 
Gardasil®9, Gardasil 9 
HPV 9-valent vaccine, recombinant 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte-colony stimulating factor 
GM-CSF 
Granulocyte macrophage-colony stimulating factor 
GMP 
Good Manufacturing Practice 
HPV 
Human papillomavirus 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
IRB 
Institutional review board 
LFT 
Liver function test 
LQI 
Life Quality Index 
Confidential
Page 1234

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 11 of 115 
Abbreviation  
Explanation 
MM 
Multiple myeloma 
NCI 
National Cancer Institute 
NHL 
Non-Hodgkin’s lymphoma 
NIH 
National Institutes of Health 
NOAEL 
No observed adverse effect level 
PBMC 
Peripheral blood mononuclear cells 
PD 
Pharmacodynamic(s) 
P-gP 
P-glycoprotein 
PHB 
p-hydroxybenzoate salt 
PK 
Pharmacokinetic(s) 
PT 
Preferred term 
QD 
Once daily 
SAE 
Serious adverse event 
SF-36 
36-item Short Form Survey 
SOC 
System organ class 
SUSAR 
Suspected, unexpected serious adverse reaction 
T1/2 
Half-life 
TAT 
Time above threshold 
TDaP 
Tetanus, diphtheria, and pertussis vaccine 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
TLT 
Treatment-limiting toxicity 
TMF 
Trial master file 
ULN 
Upper limit of normal 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
WHIM 
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis 
Confidential
Page 1235

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 12 of 115 
1.
PROTOCOL SYNOPSIS
Study title 
A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor in Patients 
with WHIM Syndrome 
Study number 
X4P-001-MKKA 
Sponsor 
X4 Pharmaceuticals, Inc. 
61 North Beacon Street, 4th Floor 
Boston, MA 02134 
Phase 
2 
Planned study period 
(first enrollment-last 
patient out) 
First patient in: Q1 2017 
Expected last patient, last visit: Q1 2023 (study may end early if the 
product is commercially available or if the study is terminated by the 
Sponsor for any reason). 
Study objectives 
The primary objectives of the initial Treatment Period are: 
•
To evaluate safety and tolerability of mavorixafor in patients with
WHIM syndrome.
•
To assess the dose required to achieve a consistent increase in
circulating neutrophils and lymphocytes in those patients.
The objectives of the Extension Phase are: 
•
To evaluate the safety of long-term treatment with mavorixafor.
•
To evaluate the efficacy of long-term mavorixafor treatment on
infection rate, skin warts, vaccine titers, and neutrophil and
lymphocyte counts.
Confidential
Page 1236

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 13 of 115 
Study design and plan 
Protocol X4P-001-MKKA is a Phase 2 study with an initial 24-week 
Treatment Period and an Extension Phase. 
This study is designed to determine the safety, tolerability, and dose 
selection of mavorixafor for Phase 3 in patients with WHIM syndrome. 
Eligible patients will initiate treatment with mavorixafor at 50 mg once 
daily (QD) or a higher dose, with potential escalation based on area under 
the curve for absolute neutrophil count and absolute lymphocyte count 
(AUCANC/ALC) values to a maximum total daily dose of 400 mg. 
Additional twice daily (BID) dosing schedules may be explored but total 
daily dose will not exceed 400 mg daily. During the initial Treatment 
Period, patients will attend monthly office visits and will be monitored 
daily using an automated telephone- or web-based reporting system for 
temperature, activities of daily living, antibiotic usage, and unscheduled 
healthcare visits. Furthermore, patients will be admitted to a research unit 
at Weeks 5, 13, and 21 to permit collection of serial samples over 
24 hours for determination of white blood cells (WBC), absolute 
neutrophil count (ANC), absolute lymphocyte count (ALC), absolute 
monocyte count (AMC), and plasma drug levels. In the event that a 
patient cannot return to the research unit, serial sampling may be done by 
a visiting nurse or by the patient’s primary care physician. 
Patients may receive standard of care antibiotics in the event of infection, 
but may not receive routine extended prophylaxis with 
granulocyte-colony stimulating factor (G-CSF). In the event of an episode 
consistent with acute, severe bacterial infection, the Investigator may add 
rescue therapy consisting of a course of G-CSF (and/or immunoglobulin 
[Ig] therapy, if applicable) (see Section 7.4.4.2).  
During the initial Treatment Period, all available safety data will be 
reviewed approximately every 12 weeks by a Data Review Committee 
(DRC). After at least 4 patients have completed 24 weeks of treatment, 
the DRC will review all available data and make recommendations 
regarding the course of the study and the recommended Phase 3 dose. 
During the Extension Phase, the DRC will review data approximately 
every 6 months. 
During the Extension Phase, patients will have on-site visits every 
6 months (±30 days) for the assessment of vital signs, safety laboratory 
tests, and pregnancy tests. In addition to evaluating safety, procedures 
every 12 months (±30 days) may include assessment of warts, 
ophthalmologic assessments, revaccination, and sampling for biomarkers 
including serum immunoglobulins, specific antibodies, and trough WBC, 
ANC, ALC, AMC, pharmacokinetics (PK), and quality of life 
evaluations. 24-hour serial ANC, ALC, AMC, and dense PK sampling are 
optional at these visits. Optional patient interviews may be conducted via 
Confidential
Page 1237

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 14 of 115 
telephone on an ad-hoc basis in the Extension Phase to gain insight about 
the patient’s overall study experience and patient-reported perceived 
treatment effect. 
Subjects may also be asked to take part in optional pharmacogenetic 
research. Subjects who decline the pharmacogenetic research are eligible 
for the study if they meet all inclusion criteria and none of the exclusion 
criteria. The objective of the optional pharmacogenetic research is to 
assess how the genetic makeup of an individual affects his/her response 
to drugs, such as how CYP3A4*22 status may be associated with poor 
metabolism. 
Planned number of 
patients 
The maximum number of patients to be enrolled is up to 15 adult patients 
(aged ≥18 years). 
Diagnosis and main 
inclusion criteria 
Patients with a clinical diagnosis of WHIM syndrome must meet all of 
the following criteria to be eligible for study participation: 
1.
Be at least 18 years of age.
2.
Has signed the current approved informed consent form.
3.
Has a genotype-confirmed mutation of CXCR4.
4.
Agree to use contraception as follows:
•
For women of childbearing potential (WOCBP), agree to use
highly effective contraceptive methods from Screening,
through the study, and for at least 4 weeks after the last dose
of study drug (see Section 7.4.1.1 for the definition of non-
childbearing potential).
•
For males, agree to use a condom with any WOCBP sexual
partner from Day 1 of study treatment, through the study, and
at least 4 weeks after the last dose of study drug.
5.
Be willing and able to comply with this protocol.
6.
Has confirmed ANC ≤400/µL or ALC ≤650/µL or both, where
confirmation applies to each cell type separately and requires
meeting the criterion on at least 2 independent blood samples
collected over up to 14 days.
Extension Phase. Any patients who complete the initial 24-week 
Treatment Period may continue to receive mavorixafor in the Extension 
Phase. 
Confidential
Page 1238

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 15 of 115 
Exclusion criteria 
Patients with any of the following will be excluded from participation in 
the study: 
1. Has known systemic hypersensitivity to the mavorixafor drug 
substance or its inactive ingredients.  
2. Is pregnant or breastfeeding. 
3. Has a known history of a positive serology or viral load for HIV 
or a known history of AIDS.  
4. Has, at Screening, laboratory tests meeting one or more of the 
following criteria: 
- A positive antibody test for hepatitis C virus, unless 
documented to have no detectable viral load on two 
independent samples.  
- A positive test for hepatitis B surface antigen. 
5. Has, at Screening, safety laboratory tests meeting one or more of 
the following criteria: 
- Hemoglobin <8.0 g/dL. 
- Platelets <75,000/μL. 
- Creatinine >2.0 x the upper limit of normal (ULN). 
- Serum aspartate transaminase >2.5x ULN. 
- Serum alanine transaminase >2.5x ULN. 
- Total bilirubin >1.5x ULN (unless due to Gilbert’s 
Syndrome, total bilirubin > 3.0x ULN and direct bilirubin 
> 1.5x ULN). 
6. Has, within 2 months prior to Day 1, received Plerixafor 
(open-label or blinded) as treatment of WHIM Syndrome. 
7. Has, within the 4 weeks prior to Day 1, had surgery requiring 
general anesthesia.  
8. Has, within 2 weeks prior to Day 1, received any of the following 
treatments:  
- G-CSF or granulocyte macrophage-colony stimulating factor. 
- Immunoglobulin – Intravenous or subcutaneous (unless 
deemed necessary by the treating physician and after 
agreement from the Sponsor). 
- Corticosteroids (>10 mg prednisone equivalent per day). 
Confidential
Page 1239

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 16 of 115 
- Investigational therapies should be discussed with the 
Medical Monitor. 
9. Is currently taking or has, within 2 weeks prior to Day 1, received 
any medication that is a strong inhibitor or inducer of cytochrome 
P450 (CYP) and/or P-glycoprotein. (see Sections 7.4.1.3 and 
7.4.1.4).  
10. Has, at the planned initiation of study drug, an uncontrolled and 
active infection (excluding warts), that has the potential to raise 
the ANC counts. 
11. Has any other medical or personal condition that, in the opinion 
of the Investigator, may potentially compromise the safety or 
compliance of the patient, or may preclude the patient’s 
successful completion of the clinical study.  
Investigational 
Medicinal Product: 
dose/mode of 
administration/dosing 
schedule 
The investigational agent is mavorixafor. Mavorixafor will be provided as 
100 mg capsules. Previously, mavorixafor drug product was also 
available as a 25 mg hard gelatin capsule formulated with compendial 
pharmaceutical excipients.  
Mavorixafor is to be administered orally at a consistent time each 
morning (±2 hours) with no food or drink (except water) for at least 1 hr 
pre-dose and continuing for at least 2 hr post-dose. 
In the initial Treatment Period, 2 patients were treated at the initial 
proposed starting dose of 50 mg QD; this dose was determined to be a 
suboptimal dose. All subsequent patients received mavorixafor at a 
starting dose of 100 mg QD or a higher dose with potential escalation 
based on AUCANC/ALC values to a maximum total daily dose of 400 mg. 
Additional BID dosing schedules may be explored but total daily dose 
will not exceed 400 mg daily. 
In the Extension Phase, all patients will receive mavorixafor; the dose 
will not exceed 400 mg daily. Dose-escalation may be continued during 
the Extension Period, if necessary, after prior approval from the Data 
Monitoring Committee, based on AUCANC/ALC values, safety data, and 
review of clinical efficacy, up to a maximum dose of 400 mg daily. 
Planned treatment 
duration per patient 
Patients are expected to receive treatment for 24 weeks in the initial 
Treatment Period or until development of a treatment-limiting toxicity 
(see Section 5.7). 
In the Extension Phase, treatment may continue until commercial 
availability of mavorixafor or until the study is terminated by the Sponsor 
for any reason. 
Confidential
Page 1240

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 17 of 115 
Efficacy Endpoints: 
The primary endpoint of this study is the mean value of the AUCANC 
and/or AUCALC collected over a 24-hour period above clinically 
meaningful thresholds for the mavorixafor treated patients over 6 months. 
The ANC clinically meaningful threshold is defined as ANC ≥600/µL 
and the ALC clinically meaningful threshold is defined as ≥1000/µL. 
The exploratory endpoints are: 
• 
Time above threshold (TAT) of ANC, ALC, and AMC at 
different dose levels of mavorixafor, where: 
• 
Time above threshold for ANC (TATANC) is the time in 
hours over 24 hours during which the ANC is maintained 
above 500 cells/μL. 
• 
Time above threshold for ALC (TATALC) is the time in 
hours over 24 hours during which the ALC is maintained 
above 1000 cells/μL.  
• 
Time above threshold for monocytes (TATmono) is the 
time in hours over 24 hours during which the monocytes 
count is maintained above the lower limit of normal 
corrected for age and sex per laboratory normal ranges. 
• 
Frequency and severity of infections, with diagnosis based on 
Investigator’s clinical assessment and severity assessed as Grade 
1 to 4 using National Cancer Institute Common Terminology 
Criteria for Adverse Events. 
• 
Number of warts – applicable only to patients with cutaneous 
warts at baseline, and comparing number at baseline to number at 
end of the Treatment Period.  
• 
Severity of genital warts – applicable only to patients with genital 
warts at baseline, and comparing number of lesions, size of 
largest lesion, and patient-reported morbidity at baseline to end of 
the Treatment Period.  
• 
Antibody levels following revaccination – applicable only to 
patients who were (a) previously administered approved 
vaccines, (b) found at baseline to have predefined sub-protective 
levels of antibody, and (c) agree to repeat administration of the 
vaccine after at least 12 weeks of treatment. 
• 
Frequency of events requiring rescue therapy (G-CSF and/or Ig). 
• 
Rate of infections.  
• 
Rate of hospitalization events as compared to baseline. 
Confidential
Page 1241

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 18 of 115 
• 
Circulating WBCs:  
- Absolute and fold change from baseline in total WBC counts, 
and in absolute numbers of lymphocytes, neutrophils, 
monocytes, and lymphocyte subpopulations cells.  
- Correlation of WBC, ANC, ALC, and AMC levels with 
plasma drug levels.  
• 
Ig and specific antibodies: 
- Changes from baseline in levels of total IgG, IgG subclasses, 
IgA, IgD, IgE and IgM. 
• 
Optional bone marrow aspirates (analyzed centrally by a blinded 
reviewer): 
- Change from baseline in cellularity. 
- Change from baseline in frequency of apoptotic cells. 
• 
Quality of life as assessed by the 36-item Short Form Survey, 
Life Quality Index, and HPV Impact Profile (if applicable), 
• 
Qualitative patient interviews conducted via telephone in the 
Extension Phase by a third party (optional) (see Section 7.1.5.3) 
Statistical methods 
(includes sample size 
calculation) 
Sample Size: 
Given the rarity of the disease under study, a traditional 3+3 dose 
escalation design was not selected. Alternatively, a small number of adult 
subjects (up to 15) will be treated with mavorixafor on an open-label 
basis, with safety data reviewed on an approximately every 12-week basis 
by the DRC. 
A sample size of up to 15 patients was considered adequate for the 
objectives of assessing safety, tolerability, and preliminary efficacy for 
planned Phase 3. 
Confidential
Page 1242

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 19 of 115 
 
Statistical Methods: 
All data collected in this study will be documented using summary tables, 
figures, and/or patient data listings. For continuous variables, descriptive 
statistics (number (n), mean, median, standard deviation, minimum and 
maximum) will be presented. For categorical variables, frequencies and 
percentages will be presented. For time-to-event variables, percentages of 
patients experiencing that event will be presented and median time to 
event will be estimated using the Kaplan-Meier method. As appropriate, a 
95% CI will be presented. Graphical displays will be presented, as 
appropriate. 
For the primary efficacy endpoint, ANC and/or ALC will be analyzed as 
AUCs relative to pre-specified clinically meaning thresholds of 600/µL 
and 1000/µL, respectively. The 24-hour AUC will be calculated using the 
trapezoidal method with area above threshold being positive, and area 
below threshold, negative (see Section 10.4.2). Patients with AUCANC 
<2000 cell•hr/µL or AUCALC <5000 cell•hr/µL at the Week 5 or Week 13 
evaluations will have mavorixafor daily dose increased up to a maximum 
total daily dose of 400 mg. Subsequent dose-escalations may be 
conducted in both treatment periods after prior approval from the Data 
Monitoring Committee, based on AUCANC/ALC values, safety data and 
review of clinical efficacy, up to a maximum dose of 400 mg daily. 
Because ANC and ALC in WHIM patients are significantly impacted by 
acute infection, alone or with antibiotics, G-CSF, corticosteroids, 
epinephrine, or any other treatment that in the opinion of the investigator 
might impact cell counts, the planned in-residence stays should be 
delayed if necessary until therapy has been discontinued and the patient 
remained afebrile for at least 2 weeks. Sequential in-residence stays must 
be separated by at least 4 weeks and preferably 6 weeks. Planned 
in-residence stays should also occur no less than 14 days after any change 
of dose. 
Schedules of events 
The schedule of events is presented in Table 1-1 for the initial Treatment 
Period and in Table 1-2 for the Extension Phase. 
 
Confidential
Page 1243

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 20 of 115 
Table 1-1: 
Schedule of Events –Initial Treatment Period 
Procedure 
Study Period / Visit 
Screen-
ing2 
Initial Treatment Period1 
EOS5 6 
Day 1 
Week 23 
(± 3D) 
Week 33 
(± 3D) 
Week 43 
(± 3D) 
Week 54 
(-7D/ 
+14D) 
Week 93 
(± 7D) 
Week 134 
(± 14D) 
Week 173 
(± 7D) 
Week 214 
(± 14D) 
Week 25 
(EOT) 
(± 7D) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
X6 
X6 
General medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
History of WHIM 
syndrome  
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Genotyping for eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
ANC and ALC for 
eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
X 
 
 
 
X 
 
X 
 
 
X 
X 
Body weight 
X 
X 
 
 
 
X 
 
X 
 
 
X 
X 
Physical examination  
X 
X 
 
 
 
X 
 
X 
 
 
X 
X 
Vital signs7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety laboratory tests8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG9 
X 
X 
 
 
 
X 
 
X 
 
X 
 
 
Ophthalmologic 
examination10 
X 
 
 
 
 
 
 
X 
 
 
X 
 
Pregnancy test11 
X 
X12 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Serial WBC, AMC, ANC, 
and ALC sampling (for 
time above threshold and 
AUC)13 
 
 
 
 
 
X14 
 
X 
 
X 
 
 
Assessment of warts15 
X 
X 
 
 
 
X 
 
X16 
 
X 
 
 
Confidential
Page 1244

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 21 of 115 
Procedure 
Study Period / Visit 
Screen-
ing2 
Initial Treatment Period1 
EOS5 6 
Day 1 
Week 23 
(± 3D) 
Week 33 
(± 3D) 
Week 43 
(± 3D) 
Week 54 
(-7D/ 
+14D) 
Week 93 
(± 7D) 
Week 134 
(± 14D) 
Week 173 
(± 7D) 
Week 214 
(± 14D) 
Week 25 
(EOT) 
(± 7D) 
Serum Ig and specific 
antibodies 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
Revaccination 
 
 
 
 
 
 
 
X 
 
 
 
 
Quality of life 
questionnaires 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
PK and Biomarker Time 0 
sample17 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
PK dense sampling17 
 
 
 
 
 
X 
 
X 
 
X 
 
 
Bone marrow aspirate 
(optional)18 
X 
 
 
 
 
 
 
 
 
 
X 
 
Study drug administration 
 
X (Daily) 
 
Diary completion19 
 
X (Daily) 
 
Concomitant medication 
monitoring 
Continuous from Screening to EOS 
Adverse event monitoring 
Continuous from Informed Consent to EOS 
Abbreviations: ALC=absolute lymphocyte count; AMC=absolute monocyte count; ANC=absolute neutrophil count; AUC=area under the curve; ECG=electrocardiogram; 
EOS=End-of-Study; EOT=End-of-Treatment; HR=heart rate; Ig=immunoglobulin; PK=pharmacokinetics; WBC=white blood cell count. 
Note: Home-health visits are authorized if there are extenuating circumstances that would impede patients from coming to the study site for a scheduled visit. Requests for home 
health visits will be reviewed and approved by X4 on a case-by-case basis. Home health visits will be an option applicable for all study visits, including screening and baseline. 
1 
The schedule is presented relative to Study Week and Time of Dosing.  The calendar day of the first administration of study drug is designated Day 1.  All weeks are relative 
to Week 1, defined as Day 1 through Day 7, inclusive.  Pre-and post-dose intervals are relative to the time of oral administration, designated 0 hr. 
2 
Screening Visit and Day 1 may be done during the same visit.  
3 
Depending upon patient situation the Week 2, 3, 4, 9 and 17 vital signs and blood draws could be done at either the study site or by a visiting research nurse in the subject’s 
home. 
4 
In-residence visits are conducted at Week 5 + 14 days and Weeks 13 and 21 ±14 days. If a patient cannot return to the study site for an in-residence visit, a dense-sampling 
visit may be conducted by visiting research nurse or by the patient’s primary care physician; however, in-residence visits at the study site are preferred.  If a patient has their 
dose escalated during the Extension Phase, additional in-residence or dense-sampling visits may be conducted after the patient has received the escalated dose for at least 
2 weeks. Additional in-resident or dense-sampling visits may also be conducted in the absence of dose escalation in order to collect additional data regarding a specific dose.  
Patients will have all of the same assessments conducted at the Weeks 5, 13 and 21 visits repeated at these additional in-residence or dense-sampling visit intervals. 
5 
The EOS visit is scheduled for 30 days ± 5 days after the last dose of study drug.  
6 
Patients may be considered eligible for the Extension Phase after the EOT or EOS visit; informed consent will be completed before entry into the Extension Phase. 
Confidential
Page 1245

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 22 of 115 
7 
Vital signs comprise heart rate, blood pressure, and temperature. For patients dosed in clinic for PK dense sampling, vital signs will be performed and safety laboratory tests 
collected pre-dose. 
8 
Safety laboratory tests – hematology and chemistry; see Section 7.2.1.1 for details. Safety laboratory tests may be conducted by a central or local laboratory. 
9 
12-lead ECG to be done pre-dose on Day 1 and at 2 hours post-dose during each in-residence dense PK sampling.  
10 
Ophthalmologic examination – see Section 7.1.1.8 for details. 
11 
Women of childbearing potential only. 
12 
Women of childbearing potential (see Section 7.4.1.1 for definition) will have a urine or serum pregnancy test done at the site on Day 1 and the results obtained prior to 
dosing. 
13 
Samples to be collected during an in-residence stay.  See Section 7.1.4.1 for details of times for serial WBC, ANC, ALC, and AMC blood samples.  
14 
WBC, ANC, ALC, and AMC performed by a Central Laboratory determined by the Sponsor. 
15 
Wart assessment details are further described in Section 7.1.1.7. 
16 
After consultation with the medical monitor, treatment with imiquimod to a sub-set of warts. 
17 
See Section 7.1.2, and Section 7.1.3 for details of times and permitted variances for collection of PK and biomarker blood samples at time 0 and during dense sampling.  
18 
Bone marrow aspirates are considered optional for this study (see Section 7.1.1.3). 
19 
Daily diary for study drug administration, temperature, activities of daily living, antibiotic usage, and unscheduled healthcare visits for infection. 
 
 
Confidential
Page 1246

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 23 of 115 
Table 1-2: 
Schedule of Events – Extension Phase 
Procedure 
Office Visits:  
Every 6 Months 
(±30 days) 
Office Visits:  
Every 12 Months 
(±30 days) 
End of Study 
(30 days ±5 days) 
Body weight 
 
X 
X 
Physical examination 
 
X 
X 
Vital signs (HR, BP, temp) 
X 
X 
X 
Safety laboratory tests (Section 7.2.1.1) 
X 
X 
X 
Pregnancy test (WOCBP only) 
X 
X 
X 
Ophthalmological examination 
(Section 7.1.1.8) 
X 
 
 
Mavorixafor metabolite assessment1 
 
X1 
 
Trough WBC, ANC, ALC, AMC, and PK 
sampling 
 
X 
 
ANC, ALC, and AMC sampling for time 
above threshold and AUC (optional) 
(Section 7.1.4.1) 
 
X 
 
PK dense sampling (optional) 
(Section 7.1.2) 
 
X 
 
Assessment of warts 
 
X 
 
Serum Ig and specific antibodies 
 
X 
 
Revaccination (optional) (Section 7.1.1.4) 
 
X 
 
Biomarker Time 0 sample (Section 7.1.3) 
 
X 
 
Study drug administration 
Continuous 
 
Diary completion2 
Continuous 
 
Concomitant medication monitoring 
Continuous 
 
Adverse event monitoring 
Continuous 
Quality of life questionnaires 
 
X 
 
Pharmacogenetic sampling (optional)3 
X3 
 
Qualitative patient interview conducted 
by a third party (optional) (Section 
7.1.5.3) 4 
X4 
 
Research blood (optional) 
X 
X 
 
Abbreviations: ALC=absolute lymphocyte count; AMC=absolute monocyte count; ANC=absolute neutrophil count; AUC=area 
under the curve; BP=blood pressure; HR=heart rate; Ig=immunoglobulin; PK=pharmacokinetic; WBC=white blood cell; 
WOCBP=women of childbearing potential. 
I 
I 
Confidential
Page 1247

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 24 of 115 
Note: Home-health visits are authorized if there are extenuating circumstances that would impede patients from coming to the 
study site for a scheduled visit. Requests for home health visits will be reviewed and approved by X4 on a case-by-case basis. 
Home health visits will be an option applicable for all study visits, including screening and baseline. 
1. 
A single sample will be obtained for evaluation of mavorixafor metabolites at the yearly visit (e.g., Month 12, 24, etc.), 
whichever occurs earliest for each patient after implementation of the v5.0 protocol amendment. 
2. 
Daily diary for study drug administration, temperature, activities of daily living, antibiotic usage, and unscheduled 
healthcare visits for infection. 
3. 
Optional assessment that may occur one time during the course of the study. 
4. 
The qualitative patient interview can be performed by telephone at any time during the Extension Phase. For additional 
details see Section 7.1.5.3. 
 
 
Confidential
Page 1248

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 25 of 115 
Table 1-3 
Estimated Blood Volume - Initial Treatment Period 
Tests 
Vol 
(mL) 
Scrn 
Day 1 
Study Week2 
EOS 
Total 
Vol 
(mL) 
2, 3, 4 
5 
9 
13 
Week 
17 
Week 
21 
Week 
25 
(EOT) 
WBC, ANC, ALC, and AMC Dense 
Sampling 
2 
 
 
 
20 
 
20 
 
20 
 
 
60 
Safety Laboratory Tests  
8 
8 
8 
24 
8 
8 
8 
8 
8 
8 
8 
96 
Pharmacokinetic Samples3 
2 
 
2 
 
22 
2 
22 
2 
22 
2 
 
74 
Biomarker Samples 
16 
 
16 
 
 
16 
 
16 
 
16 
 
64 
Pregnancy test (WOCBP only)4 
0 
0 
05 
 
0 
0 
0 
0 
0 
0 
0 
0 
Serology 
0 
0 
 
 
 
 
 
 
 
 
 
0 
Serum Ig and Specific Antibodies 
17 
 
17 
 
 
17 
 
17 
 
17 
 
68 
Total mL blood drawn 
 
8 
43 
8/week 
50 
43 
50 
43 
50 
43 
8 
362 
Abbreviations: ALC=absolute lymphocyte count; AMC=absolute monocyte count; ANC=absolute neutrophil count; EOS=End-of-Study; EOT=End-of-Treatment; 
Ig=immunoglobulin; PK=pharmacokinetics; WBC=white blood cell; WOCBP=women of childbearing potential. 
1 
The volumes shown are estimates; final volumes may vary, but will not be more than 15% greater than shown.   
2 
The schedule is presented relative to Study Week and Time of Dosing. The calendar day of the first administration of study drug is designated Day 1. All weeks are relative to 
Week 1, defined as Day 1 through Day 7, inclusive. 
3 
See Section 7.1.2 for PK sampling times. 
4 
Pregnancy testing will be done at the central laboratory. Extra blood volume is not required.  
5 
Day 1 pregnancy test is done locally and may be performed on either a blood or urine sample. 
Confidential
Page 1249

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 26 of 115 
Table 1-4: 
Estimated Blood Volume - Extension Phase  
Tests 
Vol 
(mL) 
Office Visits: Every 
6 months 
Office Visits: Every 
12 months  
EOS 
Total 
Vol 
(mL) 
ANC, ALC, and AMC Dense Sampling 
(optional) (Section 7.1.4.1) 
2 
 
20 
 
20 
Safety Laboratory Tests (including trough 
WBC/ANC/ALC/AMC/pregnancy 
test/serology) 
8 
8 
8 
8 
24 
Trough PK sample 
2 
 
2 
 
2 
Serial PK Samples (optional) (Section 
7.1.2)  
2 
 
22 
 
22 
Mavorixafor metabolite sample1 
3 
 
31 
 
31 
Biomarker Samples 
16 
 
16 
 
16 
Serum Ig and Specific Antibodies 
17 
 
17 
 
17 
Optional Research Blood (Section 
7.1.4.3) 
102 
102 
102 
 
102 
Total mL blood drawn 
 
8 
851 
8 
1011 
Abbreviations: ALC=absolute lymphocyte count; AMC=absolute monocyte count; ANC=absolute neutrophil count; EOS=End-
of-Study; Ig=immunoglobin; PD=pharmacodynamics; PK=pharmacokinetic; WBC=white blood cell. 
Notes: The volumes shown are estimates; final volumes may vary, but will not be more than 15% greater than shown. The total 
volume accounts for a 1-year period, one office visit for safety only and one more extensive office visit for safety, PK, and PD 
assessments at 6-month (±30 days) intervals to evaluate vital signs, safety laboratory parameters, and pregnancy tests) plus the 
EOS; amounts will be higher based on duration of participation. 
1 
Optional serial dense sampling assessments blood volumes are included in the total blood volume estimate. A single 3 mL 
sample will be obtained for evaluation of mavorixafor metabolites at the yearly visit (e.g., Month 12, 24, etc.), whichever 
occurs earliest for each patient after implementation of the v5.0 protocol amendment. The total blood volumes do not show 
this 3 mL sample because it will occur only once in the study and not at every 12-month visit. 
2 
For patients who consent to future research, blood may be collected and stored to better understand the immunological 
response in patients with WHIM syndrome. The total blood volumes do not show the research sample because it is optional. 
See Section 7.1.4.3. 
 
Confidential
Page 1250

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 27 of 115 
SCHEMATIC OF THE STUDY DESIGN 
Figure 1-1: 
Dose Titration Strategy and Visit Schedule--Initial Treatment Period 
 
Abbreviations: ALC=absolute lymphocyte count; ANC= absolute neutrophil count; AUC=area under the curve; 
DMC=Data Monitoring Committee; PD=pharmacodynamics; PK=pharmacokinetic; QD=once daily; SAE=serious 
adverse event. 
Notes: Maximum daily dose not to exceed a total daily dose of 400 mg.  
**In the initial treatment period, the first 2 patients were treated at the starting dose of 50 mg QD; this dose was 
determined to be a suboptimal dose as it did not increase ANC and ALC above pre-determined thresholds. All 
subsequent patients therefore received mavorixafor at a starting dose of at least 100 mg QD. 
Based on the emerging safety PK and PD data, escalation may continue beyond the initial treatment period after 
approval from the DMC and even if patients meet the above-mentioned AUC threshold criteria to determine the 
Phase 3 dose that will provide the most consistent increase in circulating neutrophils and lymphocytes in the most 
number of patients. However, the maximum daily dose will be ≤400 mg. Patients who experience a ≥ Grade 3 
treatment-related SAE will not be escalated. 
Figure 1-2: 
Overall Study Design--Initial Treatment Period and Extension Phase 
 
Abbreviations: AUCANC/ALC= area under the curve for absolute neutrophil count and absolute lymphocyte count; 
QD=once daily. 
*Dose-escalations may be conducted in both treatment periods based on AUCANC/ALC values, safety data, and 
review of clinical efficacy, up to a maximum dose of 400 mg daily. 
All patients start 
X4P-001 at 100•• 
mgQD 
Day 
1 
Screening 
24-Hour 
AUCANC 
and/or 
AUCALC 
Threshold not met: 
Escalate dose by 
100mg 
Threshold met: 
Continue at same 
dose level 
Week 
5 
Threshold not met: 
Escalate dose by 
100mg 
24-Hour 
AUCANC 
and/or 
AUCALC 
Threshold met: 
Continue at same 
dose level 
Week 
13 
Continuous safety monitoring and DRC safety review 
24 W eeks 
r 
.... 
--+ 
Initial Treatment Period 
Encl of 
(mavorixafor, up to 400 mg QD) 
Study 
\.. 
.i 
' 
Exit 
24-Hour 
AUCANC 
and/or 
AUCALC 
r 
\. 
No dose escalation: 
Continue at same 
dose level 
Week 
21 
Extension Phase 
{Office visits every 6 mos; 
phone contacts between 
visits) 
Encl of 
Study 
...,, 
Confidential
Page 1251

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 28 of 115 
2.
INTRODUCTION:  BACKGROUND INFORMATION AND
SCIENTIFIC RATIONALE
2.1. 
Background Information
WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is 
exceedingly rare. The estimated incidence is 0.23 per million births, based on the identification 
of 8 patients in the French national registry (Table 5) [Beaussant-Cohen 2012]. WHIM syndrome 
is associated with significant morbidity and mortality [Beaussant-Cohen 2012].  
In 1964, Zuelzer reported a young girl with severe non-cyclic neutropenia and frequent upper 
and lower respiratory tract infections. Of note, transient increases in circulating leukocytes had 
been observed during acute infection and were achieved experimentally following administration 
of bacterial endotoxin. The bone marrow demonstrated distinctive histopathological features, 
including dense hypercellularity and a predominance of hyper-mature neutrophils with highly 
condensed nuclear chromatin, increased segmentation, and cytoplasmic vacuoles [Zuelzer WW 
1964]. Zuelzer hypothesized that in contrast to neutropenia associated with inadequate 
production, the mechanism here related to inappropriate retention of white blood cells in the 
bone marrow, and proposed the term myelokathexis. Subsequent studies demonstrated that in 
myelokathexis the marrow neutrophils have increased markers of apoptosis [Aprikyan 2000].  
Based on clinical features noted in subsequent cases, the disease was designated WHIM 
syndrome [Al-Herz 2014]. In 2003 Hernandez and colleagues identified mutations in CXCR4 
(C-X-C chemokine receptor type 4) in patients with WHIM syndrome from 6 different pedigrees 
[Hernandez 2003]. The characteristic feature was frameshift or nonsense mutation that resulted 
in truncation of 10 to 19 amino acids from the C-terminus representing the cytoplasmic domain. 
Similar alternations were absent from >200 controls. The cognate ligand for CXCR4 is CXCL12 
(also referred to as SDF-1α), which is constitutively expressed on bone marrow stromal cells and 
appears to cause direct and indirect cellular adhesive interactions, leading to retention of myeloid 
cells in the marrow [Gulino 2004]. A cell-line expressing CXCR4 from a WHIM patient 
demonstrated markedly increased and prolonged intracellular signaling in response to CXCL12 
compared to wild type CXCR4, suggesting that the mutation could confer a pathologic response 
to a physiologic stimulus. Subsequent in vitro studies document impaired interactions among T 
cells and B cells from patients with WHIM syndrome, defining additional aspects of a broad 
primary immunodeficiency [Kallikourdis 2013]. 
In 2012, Cohen et al. published a summary of 51 previously reported cases plus 8 additional 
cases from the French Severe Chronic Neutropenia Registry [Beaussant-Cohen 2012]. Their 
report emphasized several distinctive features with manifestations differing across individual 
patients (Table 5). The findings from this literature review are further substantiated by the results 
from a recently published review of the literature that identified and analyzed 105 published 
cases of WHIM syndrome [Heusinkveld 2019]. Note that some of these 105 cases overlap with 
the patients identified in the aforementioned literature search. The literature review for all 105 
Confidential
Page 1252

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 29 of 115 
patients [Heusinkveld 2019] included 62 females (59%), 41 males (39), and 2 individuals whose 
gender was not reported. The distribution of the patient population comprised 50% pediatric and 
46% adult patients. The pediatric age distribution included 6 infants and 47 children (ages 
1 to18 years) and 4 (4%) individuals whose age was not reported, while the adult population 
included 48 individuals. Finally, the literature provides 5 case reports of WHIM patients treated 
with hematopoietic stem cell transplant. Only 40 (38%) of the 105 cases presented all 4 classic 
manifestations of the WHIM tetrad, while other patients presented variable combinations of 
symptoms, including those outside of the WHIM tetrad. Warts affected 58 (55%) of WHIM 
patients. 
Table 5: 
Reported Clinical Characteristics of Patients with WHIM Syndrome  
Characteristic 
Reported Cases 
1964-2012 
(N=51) 
French Registry 
Cases 
(N=8) 
Overall 
Frequency Comment 
Alive at last report 
48 
6 
92% 
 
Age at last report 
≤17 yr 
18-40 yr 
41-76 yr 
 
24 
17 
7 
 
3 
2 
1 
 
55% 
30% 
15% 
 
Died – age, cause 
31 yr – meningitis 
26 yr – lymphoma 
54 yr – lymphoma 
39 yr – metastatic 
vulvar cancer 
41 yr – lymphoma 
c/b dissem atypical 
mycobacteria 
8% 
 
1/5 deaths due to infection 
4/5 deaths were due to 
malignancy 
CXCR4 mutation 
42/441 
7/8 
94% 
2 patients were directly related 
Myelokathexis 
34/35 
8/8 
98% 
The patient wo/ myelokathexis 
had typical R334X mutation 
Warts 
31/50 
5/8 
62% 
 
IgG <600 mg/dL 
IgM <40 mg/dL 
22/34 
7/34 
3/6 
3/6 
63% 
25% 
 
ANC <500/µL2 
ALC <500/µL 
31/45 
7/29 
7/8 
7/8 
72% 
38% 
 
Infections3 
PNA & bronchiectasis 
PNA 
Other respiratory4  
Non-respiratory5 
None 
 
3/46 
27/46 
9/46 
5/46 
2/46 
 
4/8 
– 
– 
3/8 
1/8 
 
13% 
50% 
17% 
15% 
6% 
 
Age, median, 41 (range: 10-76) 
 
Abbreviations: ANC=, absolute neutrophil count; ALC=, absolute lymphocyte count; IgG=immunoglobulin G; 
IgM=immunoglobulin M; PNA=pneumonia; WBC=white blood cell.  
1. Denominator represents number of patients for whom characteristic was reported as present or absent.  
2. ANC was <1,500/µL for all 53 patients with at least one reported value. WBC counts in WHIM patients can be 
transiently elevated by acute infection, and patient status at the time lab data were obtained was often unclear.  
3. Infection categories are hierarchical and mutually exclusive, emphasizing respiratory tract infection. 
Confidential
Page 1253

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 30 of 115 
4. Other respiratory, either upper respiratory infection only or respiratory, not further specified. 
5. Non-respiratory: cellulitis (2), enteritis (2), and one each, osteitis, phlegmon, urinary tract infection, and 
“numerous.” 
The most informative laboratory assessments in patients with WHIM syndrome are prospective 
baseline data from 9 patients studied over the course of one or more days from 4 published 
treatment studies [Dale 2011; McDermott 2011; McDermott 2014; McDermott 2019]. The key 
observations from those reports include:  
• Absolute lymphocyte counts (ALC) nadir was 350-500/mm3 with diurnal variation giving 
peak values of up to 900/mm3. Such variation is consistent with observations in normal 
subjects [Suzuki 1997]. 
• Absolute neutrophil counts (ANC) were <100 to 250/mm3, with some variation. 
For these reasons, patients in this study are required to enter a research unit for a 24-hour 
pharmacokinetic (PK) and ANC/ALC assessment and resulting area under the curve (AUC) 
calculation (see Section 4.1). Overall, the clinical observations support the following key 
conclusions:  
• The most common mutation (R334X), seen in 15 (56%) of 27 pedigrees, is c1000C>T 
(CXCR4R334X) resulting in a nonsense codon at amino acid 334 and truncation of the 19 
C-terminal residues.  
• Among 54 patients with sequencing data for CXCR4 as well as clinical features of WHIM 
syndrome, mutations were found in all but one pedigree (2 individuals). Those patients 
may have other defects in CXCR4 or in signaling pathways that produce a similar 
phenotype [McDermott 2010].  
• Onset of clinical symptoms of disease is usually in early childhood, marked by an 
increase in the frequency and severity of bacterial infections.  
- At presentation, most patients (78%, 14/18) experience a severe bacterial 
infection requiring hospitalization and intravenous antibiotic therapy [Dotta 
2019]. 
- As noted, patients with WHIM syndrome typically have severe neutropenia (ANC 
<200/µL). However, patients with WHIM syndrome appear to have a lower 
incidence of severe, life-threatening acute infections than patients who have 
similar counts associated with impaired neutrophil production. This is consistent 
with the observation that during acute infection, circulating white blood cell 
(WBC) counts can increase, presumably reflecting delayed release by other 
mechanisms. 
- The pattern of infections varies in individual patients. The most common severe 
infections affect the lower respiratory tract (pneumonia, bronchitis) and can be 
due to a range of Gram-positive and Gram-negative pathogens. Of note, 6 (27%) 
Confidential
Page 1254

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 31 of 115 
of all 22 reported patients over 21 years of age had progressed to bronchiectasis 
contributing to the morbidity of the disease [Beaussant-Cohen 2012].  
-
Other common infections include the upper respiratory tract (otitis media,
sinusitis) and skin and underlying tissue (cellulitis, impetigo, folliculitis, and
abscess); less common sites include joints (septic arthritis), gums (periodontitis),
bone (osteomyelitis), urinary tract, and central nervous system (meningitis)
[Tassone 2009].
•
A unique and specific consequence of the immune disorder in WHIM syndrome is the
inability to control human papilloma virus (HPV) infection, with some patients
presenting with hundreds of HPV-induced warts, including cutaneous and genito-anal
lesions. Cutaneous warts typically develop in mid-childhood between 5 and 10 years of
age and are first noted on the hands and feet, whereas genital warts usually emerge in
young adulthood after sexual debut. Morphology may range from flat warts to classic
verruca to anogenital condylomata acuminata [Heusinkveld 2017]. Warts are treatment-
refractory, and ano-genital warts are at high risk of malignant transformation [Beaussant-
Cohen 2012; McDermott 2019] and contribute to the overall mortality of the syndrome.
Severe herpes virus infections (including varicella zoster virus, herpes simplex virus type
1 [HSV-1], and herpes simplex virus type 2) were reported in over 10% of patients.
•
The most common malignancy was lymphoma. In addition to the 3 fatal cases, there was
a fourth patient with lymphoma alive (age 40) at last report. Of the 4 cases, 2 were noted
to be Epstein-Barr virus-positive and one, Epstein-Barr virus-negative.
•
Patients with WHIM syndrome may also have congenital malformations including
Tetralogy of Fallot [Badolato 2012]. Cerebellar malformation with mild neuromotor
deficits and psychopathological dysfunction [Galli 2019] add to overall disease
morbidity.
•
Treatment Experience – Immunoglobulin (Ig), granulocyte-colony stimulating factor (G-
CSF) and antibiotic prophylaxis. Finally, because of the lack of effective therapies and
the severity of the disease, a number of hematology teams in the United States and
abroad have proposed hematopoietic stem cell transplantation as a viable treatment
intervention for WHIM syndrome [Bhar 2015; Bies 2019; Dale 2020; Kriván 2010;
Moiseeva 2019].
Case reports since the mid-1990s have described administration of G-CSF and Ig (intravenously 
or subcutaneously) with the goal of preventing or modulating infection. G-CSF consistently 
increases peripheral ANCs, but has little, if any, impact on lymphopenia. The clinical effect has 
been highly variable; among the 4 patients in the French registry treated with G-CSF, 3 were 
reported to show little benefit [Beaussant-Cohen 2012]. In addition, treatment-limiting 
complications, including bone pain, have been described [Amgen, Inc., 2015].  
Confidential
Page 1255

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 32 of 115 
Immunoglobulin, as expected, raises Ig levels, but has no impact on circulating leukocytes. It has 
appeared to be helpful in young children, but long-term effectiveness has not been demonstrated. 
Although Ig replacement improves hypogammaglobulinemia and may be thought to be clinically 
beneficial, some treated patients still suffer recurrent infections, possibly because this treatment 
has no effect on associated monocytopenia or lymphopenia. Finally, warts remain refractory to all 
treatments including surgical resection [Badolato 2017]. 
2.1.1. 
Treatment Experience – Plerixafor 
Plerixafor is a CXCR4 antagonist marketed as Mozobil® and is approved for treatment at 
0.24 mg/kg actual body weight in combination with G-CSF for up to 4 consecutive days to 
mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent 
autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple 
myeloma (MM). Plerixafor has not been approved by any regulatory agency for treatment in 
WHIM patients or for long-term use. Investigational studies conducted by Dr. David Dale at the 
University of Washington and by Dr. David McDermott at the National Institutes of Health 
(NIH) in patients with WHIM syndrome have demonstrated that plerixafor at low doses can 
increase circulating levels of both neutrophils and lymphocytes [Dale 2011; McDermott 2011; 
McDermott 2014; McDermott 2019]. These studies provide proof-of-concept for the treatment of 
WHIM patients with a CXCR4 antagonist. This off-label treatment is not available to patients 
outside of a clinical trial [NCT00967785]. 
In 2 single dose, dose-escalation studies involving 9 patients with severe neutropenia and 
lymphopenia, typically with ANC <200/µL and ALC <500/µL, prior to treatment [McDermott 
2011; McDermott 2014], single doses of plerixafor as low as 0.02 mg/kg (8% the approved dose) 
were highly effective at mobilizing neutrophils, lymphocytes (including all subpopulations), and 
monocytes from the bone marrow into the circulation (Table 6). Lymphocytes, especially B cells 
(CD19+), had the greatest relative increases. The duration of the effect was dose-dependent and 
also was consistent with the short half-life (T1/2) of plerixafor (~5 hrs), supporting chronic 
dosing. All of these observations support the hypothesis that the mutations of CXCR4 render the 
receptor hyper-reactive to its ligand and that modest levels of an effective antagonist can have a 
salutary effect.  
Confidential
Page 1256

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 33 of 115 
Table 6: 
Estimated Changes in WBC in Patients with WHIM Syndrome during 
Treatment with Plerixafor1 
Reference 
N 
Condition 
Total WBC  
(106 / µL) 
ANC  
(106 / µL) 
ALC  
(106 / µL) 
Notes 
Dale, 2011 
6 
Baseline 
900 
250 
410 
 
 
 
Peak after 0.02 to 
0.24 mg/kg 
11.6x 
8.2x 
14x 
incr B cells, 40x 
McDermott, 
2011 
3 
Baseline 
1,102 
150 
350 
 
 
 
Peak after 0.02 mg/kg 4,455 
821 
3,564 
 
 
 
Peak after 0.16 or 
0.24 mg/kg 
8,100 
2,310 
4,696   
incr CD4, 6.7x;  
incr CD8, 4.5x,  
incr CD19, 40x 
McDermott, 
2014 
3 
Baseline 
~750 
~150 
350 – 9002 
Same 3 patients as Dale 
2011 
 
 
Peak after 1st dose 
0.02 mg/kg  
~3,000 
250 – 600 
~2,500 
 
 
 
After 6 mo. 0.02 mg/kg BID  
 
 
 
 
 
Post-dose peak 
Post-dose trough 
~4,000 
~2,000 
600 – 1,700 
400 – 800 
~2,500 
~900 
 
Abbreviations: ALC=absolute lymphocyte count; ANC=absolute neutrophil count; BID=twice daily; WBC=white 
blood cells.  
1. Data are presented differently in each report. In some instances, results shown have been read from graphs or 
calculated based on reported changes from baseline. For Dale 2011 and McDermott 2011, results shown 
represent mean counts or mean fold increases from baseline, as indicated. For McDermott 2014, results shown 
represent midrange of multiple values presented for each condition, with variability both within and among 
patients. 
2. McDermott 2014 presents multiple pre-treatment values over 48 hrs showing diurnal variation with morning 
troughs <350/µL in all patients. Such variation is consistent with observations in normal subjects [Suzuki 1997]. 
Chronic administration of plerixafor is hampered by the fact that it has to be given by 
subcutaneous injection and has a very short T1/2 of ~5 hrs. Additionally, as detailed above, the 
approved label (for MM and NHL indications) provides for up to 4 consecutive days of dosing in 
combination with G-CSF. During the investigational NIH dose-escalation study [McDermott 
2011] conducted in 3 patients (ages 30 to 51 years) who self-administered plerixafor at 0.01 or 
0.02 mg/kg twice daily (BID) for 6 months [McDermott 2014], both G-CSF and intravenous Ig 
were stopped. While there were quantitative differences among the leukocyte responses, several 
common themes emerged:  
• The most profound and immediate response was an increase in ALC, particularly B cells 
(CD19+, CD27–, IgM+). This response was observed over months of treatment, but 
levels oscillated daily, with ALC peaking at 3 hr post-dose and returning to near baseline 
by 12 hr, prior to the next dose.  
• In contrast, initial increases in ANC were modest, but levels became higher and more 
persistent with sustained treatment.  
Confidential
Page 1257

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 34 of 115 
• Safety laboratory monitoring of hemoglobin, platelets, and liver function tests (LFTs) 
throughout the 6 months of treatment revealed no pattern of adverse effects.  
When treatment with plerixafor was stopped at 6 months, circulating WBC counts approached 
baseline at variable rates ranging from 2 days to 35 days following the last dose, ranging from 
20% to 80% above WBC baseline values. This post-treatment effect may relate to the 
observation that bone marrow aspirates at 6 months had areas of normal cellularity.  
During the 6 months of treatment with plerixafor, each of the 3 patients had decreased frequency 
and morbidity from systemic infection compared to their pre-treatment experience. After 
treatment was discontinued for two to six months, patients appeared to return to their baseline 
pattern, indicating the need for chronic, life-long therapy. All patients entered the study with 
persistent warts unresponsive to the usual medical treatments. The first patient showed no 
improvement in their warts over the initial 4 months of plerixafor. Topical therapy with 
imiquimod (previously ineffective) was then added with good response not only at the lesions 
treated but at contralateral lesions as well, suggesting “an induced systemic anti-HPV immune 
response” [McDermott 2014]. The other 2 patients were treated with imiquimod and plerixafor 
and also showed improvement in their warts.  
These proof-of-concept data suggest that treatment with a CXCR4 antagonist can improve both 
circulating leukocyte levels and clinical manifestations associated with WHIM syndrome and 
support the current study design of mavorixafor for the treatment of patients with WHIM 
syndrome.  
2.2. 
Overview of Mavorixafor 
Mavorixafor was previously under development for the treatment of HIV infection based on the 
role of CXCR4 in viral entry into the cell. That program, which is presented in detail in the 
Investigator Brochure, included nonclinical toxicology studies and clinical studies using the free 
base formulation, then designated AMD11070 (mavorixafor hereafter). 
Throughout the prior clinical development program, the drug product used was capsules 
containing 100 mg of the free base. Lower dose capsules of 25 mg of the free base formulation 
have been used in the Dose-Escalation phase of the X4P-001-MKKA study. However, in the 
extension phase only 100 mg capsules will be used (see Section 6.1.2). 
2.2.1. 
Prior Clinical Studies Conducted Using Mavorixafor 
There is no prior clinical study experience with mavorixafor in patients with WHIM syndrome. 
The 4 clinical studies conducted under the prior development program included Phase 1 and 2a 
studies involved a total of 55 healthy volunteers [Cao 2008; Nyunt 2008] and 16 HIV-infected 
patients [Moyle 2009; ACTG (DIAIDS) Protocol A5210]. Table 7 shows the protocol numbers, 
titles, and related publications; Table 8 summarizes the study populations, objectives, numbers, 
dose administered, and duration. These studies demonstrated the following:  
Confidential
Page 1258

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 35 of 115 
• Oral administration of up to 400 mg BID for 3.5 days (healthy volunteers) and 200 mg 
BID for 8-10 days (healthy volunteers and HIV patients) was generally safe and well-
tolerated with no pattern of adverse events (AEs) or clinically significant laboratory 
changes.  
• T1/2 of mavorixafor is ~23 hours, supporting the use of once daily (QD) dosing (see 
Investigator’s Brochure). 
• Pharmacodynamic activity, as assessed by increases in circulating WBC, was related to 
dose and duration of treatment.  
Table 7: 
Prior Clinical Studies Conducted Using Mavorixafor – Protocol Number, 
Study Title, and Publication1  
Protocol No.  
Study Title 
Publications 
A5191 
A Phase I, Dose-Rising Study of AMD11070 in HIV-Seronegative Men to Assess 
the Safety and Pharmacokinetics After Single or Multiple Doses 
Stone 2007; 
Cao 2008 
AMD-1001  
Multicenter, dose-finding safety and activity study of AMD11070 in HIV-
infected patients carrying X4-tropic virus 
Moyle 2009 
AMD-1002  
A Study of the Pharmacokinetic Interaction between AMD11070 and Substrates 
of CYP 3A4 and 2D6 Enzymes in Healthy Volunteers 
Nyunt 2008 
ACTG A5210 
Phase IB/IIA Dose-Finding Safety and Activity Study of AMD11070 (An Orally 
Administered CXCR4 Entry Inhibitor) in HIV-Infected Subjects 
Johnson 2019 
1 
All studies were conducted between 3 Sep 2003 and 13 Jul 2006.  
Table 8: 
Prior Clinical Studies Conducted using Mavorixafor – Study Population, 
Objectives, and Exposures 
Study ID 
Study 
Population 
Study  
Objective 
Cohort 
(A5191 
only) 
N 
Gender  
M/F2 
Dose & Regimen 
(All oral) 
Duration 
A51911 
 
Healthy 
Volunteers 
Dose escalation: 
Safety, PK 
A-D 
121 
43 M, 0 Fa 
Single Dose  
50 to 400 mg 
1 day 
 
 
F, G, I 
181 
 
100 to 400 mg, BID 
3.5 days (7 doses) 
 
 
Effect of food, 
of ritonavir 
H, J, K 
321 
 
≤3 doses, 200 mg or 
400 mg each 
≤3 doses over 6 to 
17 days 
A5210 
HIV-infected 
Safety 
Viral load 
reduction 
 
6 
3 M, 3 F 
200 mg, BID 
10 days 
AMD-1001 
HIV-infected 
Safety 
Viral load 
reduction 
 
10 
9 M, 1 F 
100 mg, BID (N=2) 
200 mg, BID (N=8)  
10 days 
AMD-1002 
Healthy 
Volunteers 
Safety 
Drug-drug 
interaction 
 
12 
9 M, 3 F 
200 mg, BID 
8 days 
Abbreviations: BID=twice daily; F=female; ID=identification; M=male; PK=pharmacokinetic(s). 
Confidential
Page 1259

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 36 of 115 
1. Study A5191 enrolled 10 cohorts totaling 68 subjects representing 43 unique individuals. There were 3 subjects 
in each of the 4 single dose escalation cohorts (A-D) and 6 subjects in each of the 3 multiple dose escalation 
cohorts (F, G, I). No subject was enrolled in more than one of the dose escalation cohort. 
2. Within each study the median age was ~40 years; overall age range was 19 to 58 years.  
2.2.2. 
Clinical Pharmacology of Mavorixafor 
2.2.2.1. 
Clinical Pharmacokinetics 
In the 4 previous clinical studies conducted by AnorMed and NIH (Studies AMD1001, 
AMD1002, A5191, and A5210) using the freebase formulation in normal healthy volunteers and 
patients with HIV. Drug was administered orally in all studies; multiple dose studies were 
conducted using BID dosing. In single and multiple dose escalation studies, maximum 
concentration (Cmax) and AUC increased more than dose-proportionally over 50 - 400 mg dose 
range. Mean terminal T1/2 was 22.9 hr, supporting the QD dosing regimen.  
After administration of a single dose of mavorixafor at 50 mg under fasted conditions, the PK 
parameters of mavorixafor are: 
• Mean Cmax: 134  
• Mean AUC0-24: 227 ng•hr/mL 
• Mean AUCinf: 235 ng•hr/mL 
• Median Tmax: 1.5 hr 
Steady-state PK parameters were similar in healthy volunteers (AMD-1002) and in HIV infected 
patients (A5210 and AMD-1001). The results (mean ± SD) were derived from 26 subjects, 
including both healthy volunteers and HIV-infected subjects, who received mavorixafor at 
200 mg BID for 8 to 10 days.  
• AUC0-12hr: 3735 ± 1755 ng•hr/mL  
• Cmax: 1223 ± 600 ng/mL 
• Minimum concentration (Cmin) at 12 hours: 74.3 ± 47.3 ng/mL 
• Time to maximum concentration (Tmax): 2.2 ± 0.9 hr 
For 13 subjects, daily Cmin(trough) concentrations were determined. Overall, subjects reached 
steady state by Day 6, which is consistent with the T1/2 of ~23 hr. Further, Cmin and AUC0-12 were 
strongly correlated suggesting that monitoring Cmin may provide a practical means for assessing 
drug exposure.  
X4P-001-REGA study was a phase I study in 15 healthy volunteers comparing two different 
dosing regimens: 200 mg BID and 400 mg QD (10-day treatment). The study was prematurely 
discontinued on Day 3 due to an insufficient number of patients remaining on the trial to assess 
Confidential
Page 1260

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 37 of 115 
the statistical endpoints. In this study, PK samples were collected from 0-12 hr for BID dosing 
and 0-24 hr for QD dosing. Preliminary PK results are listed below.  
Following administration of mavorixafor 200 mg BID and 400 mg QD on Day 1, the mean Cmax 
were 1070 ng/mL and 2662 ng/mL, respectively; the median Tmax were 2.5 hr and 1.5 hr 
respectively. AUC0-12 was 3682 ng•hr/mL after 200 mg BID dose and AUC0-24 was 
9421 ng•hr/mL after 400 mg QD dose. Comparing with results from Study A5191, the exposure 
in REGA study is higher. 
2.2.2.2. 
Effect of Food on Absorption 
In a food-effect study (A5191), 9 male subjects received mavorixafor in the fasted stated (fasting 
overnight after midnight until 2 hours post-dose) and in the fed state (low fat meal within 30 
minutes prior to dosing), food had a significant negative effect on the bioavailability of 
mavorixafor. Cmax and AUC0-12 in the fed state was 0.33x and 0.44x of that observed in the fasted 
state, respectively. Tmax was delayed from 1 hr (fasted) to 3 hr (fed). T1/2 was not changed.  
2.2.2.3. 
Potential for Drug-Drug Interactions  
Two clinical studies were conducted to assess the potential for drug-drug interactions. Ritonavir 
(a strong CYP3A4 inhibitor, P-glycoprotein [P-gp] inhibitor) resulted in a modest increase in 
mavorixafor plasma concentrations [A5191, Cao 2008]. The mean Cmax and AUC of mavorixafor 
coadministered with the first dose of ritonavir were increased by 39% and 60%, respectively, 
compared to the administration of mavorixafor alone. Similar effects were seen after ritonavir 
had been administered BID for 14 days.  
Study AMD-1002 assessed the effect of mavorixafor on metabolism of CYP3A4 and CYP2D6 
substrates, using midazolam and dextromethorphan as substrates [Nyunt 2008]. Administration 
of mavorixafor had the following effects.  
• The Cmax for midazolam (a CYP3A4 substrate) was unaffected; AUC was 1.33x baseline. 
• The Cmax for dextromethorphan (a CYP2D6 substrate) was 2.5x baseline; the AUC, 2.86x.  
The magnitude of the midazolam interaction was modest. The magnitude of the effect on 
dextromethorphan has significant potential to result in changes in clinical drug response, 
affecting either efficacy or toxicity. The clinical study protocols include detailed restrictions on 
concomitant medications to minimize the potential for drug-drug interactions.  
Mavorixafor appeared to be a substrate of P-gp with an efflux ratio of 14. Inhibitors or inducers 
of P-gp may affect the concentration of mavorixafor in plasma or the distributions to tissues that 
express a high level of P-gp. 
2.2.2.4. 
Clinical Pharmacodynamics 
A primary pharmacodynamic effect of CXCR4 antagonism is mobilization of WBC (including 
both myeloid and lymphoid cells) from the bone marrow into the peripheral circulation. The 
relationship between plasma drug levels and concurrent peripheral blood WBC counts was 
Confidential
Page 1261

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 38 of 115 
examined in Phase 1 studies with dense sampling [Stone 2007]. After dosing, circulating WBC 
counts increased from baseline in all subjects, peaking between 2 and 4 h following dosing. The 
distribution of concurrent WBC-fold change from baseline versus drug concentration best fit a 
sigmoid maximum exposure (Emax) model.  
• The estimated Emax was WBC increase to 2.03x baseline (95% CI, 1.95x to 2.11x).  
• The estimated half maximal effective concentration was 39 ng/mL (95% CI, 28 to 
50 ng/mL), which is below the observed steady-state Cmin(12h) for mavorixafor at 200 mg 
BID, the starting dose in the proposed oncology studies.  
2.2.3. 
Clinical Safety Experience with Mavorixafor 
2.2.3.1. 
Safety Experience – X4 Pharmaceuticals Clinical Development Program  
As of 14 May 2020, the following studies have been initiated or completed:   
• X4P-001-RCCA – a Phase 1/2 study of mavorixafor alone and in combination with 
Axitinib in patients with advanced renal cell carcinoma.  
• X4P-001-RCCB – a study adding mavorixafor to patients receiving nivolumab for 
treatment of advanced clear cell renal cell carcinoma.  
• X4P-001-MELA – a Phase 1b study of mavorixafor alone and in combination with 
pembrolizumab in patients with advanced melanoma. 
• X4P-001-REGA – a Phase 1 study in healthy volunteers comparing 2 different dosing 
regimens of mavorixafor: 200 mg BID versus 400 mg QD.  
• X4P-001-MKKA – a Phase 2 trial of mavorixafor in patients with WHIM (Warts, 
Hypogammaglobulinemia, Infections and Myelokathexis) Syndrome. 
• X4P-001-103 – a blinded randomized study against placebo controlled Phase 3 trial of 
mavorixafor in patients with WHIM Syndrome. 
Please refer to the current Investigator’s Brochure for more information related to mavorixafor’s 
clinical safety data. 
2.2.3.2. 
Safety Experience – Prior Development Program 
As of 14 May 2020, 194 patients were treated with mavorixafor in 10 clinical studies 
(n= 70 healthy volunteers, n= 16 HIV, n= 99 oncology, n= 9 WHIM syndrome). Section 2.2.3.2 
summarizes the safety of the healthy volunteers and patients with HIV and Section 2.4 
summarizeds the safety of ongoing WHIM and oncology studies. 
An X4-sponsored study in 15 healthy volunteers has been completed (X4P-001-REGA). Further, 
under the prior development program (sponsored by AnorMed), 4 clinical studies were 
conducted with mavorixafor (then designated AMD-11070): AMD-1001, AMD-1002, A5191, 
Confidential
Page 1262

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 39 of 115 
and A5210. Overall, these 5 studies involved a total of 70 healthy volunteers (Studies X4P-001-
REGA, A5191, and AMD-1002) and 16 HIV-infected subjects (Studies AMD-1001 and A5210).  
• The most common clinical treatment-emergent adverse events (TEAEs) across these 
5 studies were in the gastrointestinal disorders system organ class (SOC). Across all 
studies, most of the events were mild and of brief duration; events such as diarrhea and 
nausea were typically assessed as moderate primarily because they were treated with 
routine medications.  
• Furthermore, headache was reported in all studies. The events of headache were typically 
mild or moderate in severity and short-lived. 
• Prompted by observations in the nonclinical toxicology studies in dogs, a detailed by 
subject analysis of clinical AEs related to the liver was performed. Across the studies, 
only 1 AE related to the liver was reported (“tender hepatomegaly”). This event occurred 
in an HIV-infected subject and was assessed as unrelated to study drug. The subject had 
pre-treatment transaminase levels 1.3× to 2.3× the upper limit of normal (ULN); these 
decreased to within normal limits during treatment. Total bilirubin was within normal 
limits during the entire study. 
• There were no deaths and no discontinuations due to AEs. Two subjects discontinued for 
personal reasons after receiving 1 or 2 doses of mavorixafor. 
• There was 1 serious adverse event (SAE), a grand mal seizure in a subject with a history 
of epilepsy; there were no events of seizure reported in other subjects. This SAE was the 
only clinical AE assessed as severe (Grade 3). 
• There was one other clinically notable AE. A subject with baseline bradycardia 
experienced an episode of syncope upon standing rapidly. The episode resolved promptly 
without lying down. There were no events of syncope reported in other subjects. 
• There were no laboratory abnormalities assessed as clinically significant. The primary 
treatment-related laboratory abnormalities observed were the pharmacologically expected 
increase in circulating neutrophils and lymphocytes. Treatment-emergent elevation in 
lipase was observed in one asymptomatic patient; the source of the enzyme (pancreas or 
salivary glands) was unclear. 
• A detailed by-subject analysis of abnormal LFTs revealed no pattern of treatment-
emergent LFT abnormalities suggesting a drug effect. 
2.2.4. 
Treatment Effect of Mavorixafor in Prior Clinical Studies 
There are no prior clinical studies of mavorixafor in patients with WHIM syndrome.  
Confidential
Page 1263

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 40 of 115 
2.2.5. 
Nonclinical Toxicity Studies of Mavorixafor 
Pivotal nonclinical toxicity studies were conducted in rats and Beagle dogs with mavorixafor 
administered orally in divided doses, BID. The no observed adverse effect level (NOAEL) in the 
4-week rat study was 125 mg/kg/day. Adverse effects at 250 mg/kg/day included decreases in 
food consumption, body weight, and reticulocyte counts and minimal bone marrow 
hypocellularity; all except body weight were resolved following a 14-day recovery period.  
The dose levels in the 13-week toxicity study in dogs were 10, 20, 35, and 70 mg/kg/day. 
Microscopic liver findings of pigment deposition and inflammation were reported in all dose 
groups and across males and females; these findings were typically assessed as minimal and not 
associated with histopathologic findings of necrosis or with LFT changes. The NOAEL 
(<10 mg/kg/day) reflected the finding of an isolated focus of liver necrosis (slight) in a single 
male animal dosed at 10 mg/kg/day. None of the remaining 11 animals (5 males and 6 females) 
in the 2 lowest dose groups had other liver-related findings and none, including the male with 
focal necrosis, had treatment-emergent increases in LFTs. 
At the 2 highest dose levels (35 and 70 mg/kg/day), 4 of 12 animals were reported to have 
microscopic liver changes of multifocal necrosis (minimal to slight), further characterized as 
single cell necrosis in 2 animals. Two of the 12 animals in those dose groups (both 
70 mg/kg/day) showed post-treatment increased alanine transaminase (ALT), rising to 1.4x 
above the upper range of controls in a male with no histologic findings, and to 2.4x in a female 
with multifocal single cell necrosis (slight). There were no elevations in bilirubin in any animal. 
One male (35 mg/kg/day) had “focally extensive (moderate)” necrosis and inflammation 
associated with macroscopic discoloration of the liver; transaminases were normal. On review, 
this lesion was qualitatively different from the microscopic multifocal lesions in other animals 
and had a subcapsular location, consistent with being secondary to external trauma.  
The Sponsor has completed a 9-month preclinical good laboratory practice-compliant toxicology 
study (Study X4-TOX- 0001) in Beagle dogs with interim sacrifices at 3- and 6-months and 
terminal sacrifice at 9-months. In this study, the primary mavorixafor-related microscopic 
finding was dose dependent accumulation of pigment consistent with lipofuscin in multiple 
organs at doses of 3.8 mg/kg/day and above. Additional mavorixafor-related findings in the liver 
were primarily observed at doses of 34.1 mg/kg/day and included centrilobular hepatocellular 
atrophy and sinusoidal dilation, increased severity of mononuclear cell infiltration, and bile duct 
hyperplasia. Overall, there was no meaningful elevation of circulating hepatic enzymes reflective 
of liver injury or active inflammatory response in these animals. 
During the earlier studies, a p-hydroxybenzoate salt (PHB) salt form of the drug (designated 
AMD11070PHB) was identified for future manufacturing and development purposes.  However, 
animal toxicology studies (13- and 26-week duration) with AMD11070PHB demonstrated 
unexpected findings, including retinal changes in albino rats treated for 26 weeks and notable 
gastrointestinal intolerance and liver changes in Beagle dogs treated for 13 weeks (see 
Investigator’s Brochure). Although AMD11070PHB was never administered to humans and is 
Confidential
Page 1264

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 41 of 115 
not proposed for use in any clinical studies with mavorixafor, these observations were carefully 
considered in the safety monitoring plans for all clinical studies with X4P‑001 (see Section 8.6). 
Following these findings, however, close monitoring for eye toxicities and regularly scheduled 
ophthalmologic examination were part of all clinical studies with mavorixafor (see Table 17).  
Regarding ophthalmology, the recently completed 9-month toxicology study in dogs showed no 
retinal findings, and the review of 194 clinical subjects found no retinal disorder, except for 
1 patient in Study X4P-001-RCCA with Grade 1 age-related macular degeneration and Grade 1 
retinal pigmentation at screening, and 1 patient in Study X4P-001-RCCA with Grade 1 retinal 
hemorrhage and Grade 1 retinal vein occlusion, both of which an ophthalmologist evaluated to 
be related to the patient’s pre-existing conditions (diabetes mellitus and hypertension). Central 
review of retinal images in 23 subjects, including 3 patients exposed to mavorixafor for more 
than 2 years, showed no findings. 
2.3. 
Clinical Experience with Related Compounds 
The only approved agent that blocks the CXCR4 receptor is Mozobil® (plerixafor), which is an 
injectable drug with a very short T1/2, and is approved for courses of up to 4 consecutive days in 
combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for 
collection and subsequent autologous transplantation in patients with NHL and MM. Plerixafor 
is not approved as a treatment for patients with WHIM syndrome. However, investigational 
proof-of-concept studies conducted by Dr. David Dale at the University of Washington and by 
Dr. David McDermott at the NIH in patients with WHIM syndrome have demonstrated that 
plerixafor at low doses can increase circulating levels of both neutrophils and lymphocytes [Dale 
2011; McDermott 2011] (see Section 2.1.1 for details).  
2.4. 
Updated Clinical Experience with Mavorixafor in WHIM Patients 
Prior to this clinical study, there was no experience with mavorixafor in patients with WHIM 
syndrome (Section 2.2.1).  
Detailed below are the key findings based on the experience of mavorixafor in WHIM syndrome 
enrolled in the X4P-001-MKKA and X4P-001-103 studies: 
Confidential
Page 1265

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 42 of 115 
The first 2 patients enrolled in this X4P-001-MKKA study received the starting dose of 
mavorixafor at 50 mg QD and were serially dose escalated to 100 mg QD and 150 mg QD based 
on their ANC and ALC not achieving the clinical threshold measured at the pre-determined time 
points. The Data Review Committee (DRC) met on 24 April 2017 and agreed to change the 
starting dose for additional patients to 100 mg QD as 50 mg QD did not provide sufficient 
pharmacodynamic changes in patients and was considered to be a suboptimal dose. 
As of 14 May 2020, 9 patients with WHIM syndrome have been treated with mavorixafor in 
2 clinical studies. The preliminary safety results show that treatment with mavorixafor is well 
tolerated. 
• Eight patients with WHIM syndrome in Study X4P-001-MKKA were treated with 
mavorixafor administered at doses from 50 to 400 mg QD in an open-label 24-week period 
followed by an extension study. 
• One patient with WHIM syndrome in Study X4P-001-103 was treated with mavorixafor 
administered at a dose of 400 mg QD or placebo for a 52-week treatment period followed 
by open-label mavorixafor 400 mg QD.  
On the X4P-001-MKKA study, patients with WHIM syndrome have received mavorixafor for a 
median duration of 839 days (range 94 days to 2+ years) at doses of 50 to 400 mg QD. 
Mavorixafor has been well-tolerated with no serious Grade 4 or Grade 5 AEs reported in Study 
X4P-001-MKKA. 
Seven of 8 (88.5%) patients in Study X4P-001-MKKA experienced at least 1 TEAE, 4 (50%) of 
whom experienced a total of 8 TEAEs that were considered as possibly related to study drug, 
including nausea and dyspepsia (2 patients each, 25%); and single instances of conjunctivitis, 
dermatitis psoriasiform, dry mouth, and nasal dryness (1 patient each, 12.5%). The frequency of 
TEAEs did not increase with dose. 
Overall, 2 (25%) patients experienced a total of 5 Grade 3 TEAEs. The Grade 3 TEAEs involved 
single events (12.5%) of cholecystitis, cellulitis, otitis media, procedural pain, and tibia fracture; 
no Grade 3 events were considered by the Investigator to be treatment related. No Grade 4 
TEAEs or TEAEs with an outcome of death (i.e., Grade 5 events) have been reported in Study 
X4P-001-MKKA. 
All patients demonstrated a dose-dependent increase in ANC and ALC from screening values, 
with ALC increasing in greater proportion than ANC. Mavorixafor drug exposure showed a 
dose-dependent increase correlated with AUC of neutrophils. The DRC met on 29 November 
2017 and agreed to escalate the maximum dose to 400 mg QD in order to assess if more 
consistent increases in ANC and ALC can be achieved. The basis for this recommendation 
comes from the experience of mavorixafor in oncology patients outlined below. 
The interim results from the X4P-001-MKKA study are now published [Dale 2020]. 
Healthy Volunteers 
Confidential
Page 1266

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 43 of 115 
As of 14 May 2020, a total of 70 healthy volunteers have been dosed with mavorixafor at daily 
doses ranging from 200 to 400 mg as monotherapy. In all studies, mavorixafor is considered to 
be generally safe and well tolerated, with most events being mild or moderate in severity and of 
brief duration. No deaths due to AEs occurred in any studies of healthy volunteers.  
Patients with Solid Advanced Tumors 
As of 14 May 2020, a total of 99 oncology patients have been dosed with mavorixafor at doses 
ranging from 200 to 600 mg QD as monotherapy or in combination with other agents. In all 
studies, mavorixafor is considered to be generally safe and well tolerated. The range of duration 
on treatment was 5 days to 3+ years across all patients enrolled in studies X4P-001-RCCA, 
X4P-001-RCCB, and X4P-001-MELA. 
At the discretion of the Sponsor and with agreement from the Investigator(s) and Data 
Monitoring Committee, patients in the current Phase 2 study may have their dose escalated and 
have additional in-residence or dense-sampling visits conducted during the Extension Phase. 
Additional in-resident or dense-sampling visits may also be conducted in the absence of dose 
escalation in order to collect additional data regarding a specific dose. 
Confidential
Page 1267

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 44 of 115 
3. 
OBJECTIVES AND PURPOSE 
3.1. 
Primary Objective 
The primary objectives of the initial Treatment Period are:  
• To evaluate safety and tolerability of mavorixafor in patients with WHIM syndrome. 
• To assess the dose required to achieve a consistent increase in circulating neutrophils and 
lymphocytes in those patients.  
The objectives of the Extension Phase are: 
• To evaluate the safety of long-term treatment with mavorixafor. 
• To evaluate the efficacy of long-term mavorixafor treatment on infection rate, skin warts, 
vaccine titers, and neutrophil and lymphocyte counts. 
Confidential
Page 1268

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 45 of 115 
4. 
STUDY DESIGN AND ENDPOINTS 
4.1. 
Description of the Study Design 
Protocol X4P-001-MKKA is a Phase 2 study with an initial 24-week Treatment Period and an 
Extension Phase. 
The primary objectives of this Phase 2 study are to determine the safety, tolerability, and Phase 3 
dose selection of mavorixafor in patients with WHIM syndrome. Up to 15 eligible adult patients 
(age 18 years or older) will be enrolled. Complete inclusion and exclusion criteria are presented 
in Section 5.1 and Section 5.2; the key disease-related eligibility criteria are: 
• Has a genotype-confirmed mutation of CXCR4 consistent with WHIM syndrome. 
• Has ANC ≤400/µL or ALC ≤650/µL or both on at least 2 independent blood samples 
collected over a period of up to 14 days.  
Two patients were treated at the initial proposed starting dose of 50 mg QD (see Section 2.2.3). 
This dose was determined to be a suboptimal dose. So, all additional eligible patients will initiate 
treatment with mavorixafor at 100 mg QD or a higher dose with the potential for dose escalation 
based on AUCANC/ALC values to a maximum daily dose of 400 mg. During the scheduled 
Treatment Period, patients will be continuously monitored for safety including:  
• Monthly office visits 
• Daily monitoring of temperature, activities of daily living, antibiotic usage, and 
unscheduled healthcare visits – this information will be collected using an automated 
telephone- or web-based reporting system. 
Patients are allowed to continue treatment in an Extension Phase, if regionally applicable, until it 
becomes available via an alternative mechanism (e.g., drug is commercially available, an 
expanded access program, etc. [see Section 7.3.1]) or until the study is terminated by the Sponsor 
for any reason. The dose of mavorixafor will not exceed 400 mg daily. During the Extension 
Phase, patients will have on-site visits every 6 months (±30 days) for the assessment of vital 
signs, safety laboratory tests, and pregnancy tests. In addition to evaluating safety, procedures 
every 12 months (±30 days) may include assessment of warts, ophthalmologic assessments, 
revaccination, and sampling for biomarkers including serum immunoglobulins, specific 
antibodies, and trough WBC, ANC, ALC, absolute monocyte count (AMC), PK, and quality of 
life evaluations. 24-hour serial ANC, ALC, AMC, and dense PK sampling are optional at these 
visits. Optional patient interviews may be conducted via telephone on an ad-hoc basis in the 
Extension Phase to gain insight about the patient’s overall study experience and patient-reported 
perceived treatment effect. 
Subjects may also be asked to also take part in optional pharmacogenetic research. Subjects who 
decline the pharmacogenetic research are eligible for the study if they meet all inclusion criteria 
and none of the exclusion criteria. The objective of the optional pharmacogenetic research is to 
Confidential
Page 1269

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 46 of 115 
assess how the genetic makeup of an individual affects his/her response to drugs, such as how 
CYP3A4*22 status may be associated with poor metabolism. 
Patients may receive standard of care antibiotics (and/or Ig therapy, if applicable, in the event of 
infection, but may not receive routine extended prophylaxis with G-CSF. In the event of an 
episode consistent with acute, severe bacterial infection, the Investigator may add rescue therapy 
consisting of a course of G-CSF and/or Ig therapy, if applicable (see Section 7.4.4.2). 
Prophylactic Ig therapy may be allowed after discussion with the Medical Monitor. 
During the initial Treatment period, all available safety data will be reviewed approximately 
every 12 weeks by a DRC including participating Investigator(s), an independent physician with 
relevant experience in clinical research and/or immune deficiency diseases, the Medical Monitor, 
and a representative of the Sponsor. A detailed DRC charter will be prepared. 
Patients will be admitted to a research unit at Weeks 5, 13, and 21 to permit collection of serial 
samples over 24 hours for determination of WBC, ANC, ALC, AMC, and plasma drug levels 
(PK). If patients cannot return to the study site for an in-residence visit, a dense-sampling visit 
may be conducted by visiting research nurse or by the patient’s primary care physician; however, 
in-residence visits at the study site are preferred.   
The decision for dose-escalation, if necessary, will be based on ANC and ALC analyzed as 
AUCs relative to pre-specified clinically meaning thresholds of 600/µL and 1000/µL, 
respectively. The 24-hour AUC will be calculated using the trapezoidal method with area above 
threshold being positive, and area below threshold, negative (see Section 10.4.2). Patients with 
AUCANC <2000 cell•hr/µL or AUCALC <5000 cell•hr/µL at the Week 5 or Week 13 evaluations 
will have mavorixafor daily dose increased to a maximum daily dose of 400 mg as indicated 
below:  
• Planned doses: 100 mg QD, 200 mg QD, 300 mg QD, 400 mg QD. 
• Based on the emerging safety, PK, and pharmacodynamic (PD) data, the planned dose 
may be omitted, an intermediate dose may be used to substitute the planned dose, or a 
BID dosing regimen may be explored. However, the maximum daily dose will be ≤400 
mg. 
Subsequent dose-escalations may be conducted in both treatment periods after prior approval 
from the Data Monitoring Committee, based on AUCANC/ALC values, safety data, and review of 
clinical efficacy, up to a maximum dose of 400 mg daily. Dose-escalation may occur to 
determine the Phase 3 dose that will provide the most consistent increase in circulating 
neutrophils and lymphocytes in the most number of patients. Patients who experience a ≥ Grade 
3 treatment-related SAE will not be escalated. 
Because ANC and ALC in WHIM patients are significantly impacted by acute infection, alone or 
with antibiotics, G-CSF, corticosteroids, epinephrine, or any other treatment that in the opinion 
of the investigator might impact cell counts, the planned in-residence stays should be delayed if 
necessary until therapy has been discontinued and the patient remained afebrile for at least 
Confidential
Page 1270

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 47 of 115 
2 weeks. Sequential in-residence stays must be separated by at least 4 weeks and preferably 
6 weeks. Planned in-residence stays should also occur no less than 14 days after any change of 
dose. 
After at least 4 patients have completed 12 weeks of treatment, the DRC will review all available 
data and make recommendations regarding the course of the study and the recommended Phase 
3 dose.  
4.2. 
Rationale for the Study Design, Including the Choice of Control Groups 
4.2.1. 
Rationale for the ANC and ALC Threshold 
Based on published data of WHIM patients treated with plerixafor [Dale 2011; McDermott 2011; 
McDermott 2014], baseline (pre-treatment) ANC are typically ≤250/µL, with modest variation 
over the course of the day; ALC ranges from 350 to 900/µL, representing physiologic diurnal 
variation. In the proof-of-concept study conducted by the NIH [McDermott 2014], 3 patients 
with WHIM syndrome were treated with plerixafor for 24 weeks (see Section 2.1.1 for details). 
Over that period, patients achieved a durable increase in circulating leukocyte trough values for 
ANC of approximately ≥600 cells/µL (clinically meaningful dose-escalation threshold; 
≥500 cells/µL for TATANC measurement) and for ALC, ≥1000 cells/µL. Concurrently, there was 
evidence of clinical efficacy, including:  
• A decrease in the frequency and severity of infections.  
• Improved bone marrow histology, with decreases both in hypercellularity and in the 
frequency of hypermature, apoptotic neutrophils.  
• Improved response in generalized warts following localized treatment with imiquimod 
[McDermott 2014], suggesting improved immune function, with induction of an effective 
systemic anti-HPV response. 
Although limited, these data suggest that in WHIM patients treated with a CXCR4 antagonist, 
achieving these ANC and ALC levels reflects a relevant improvement in the pathophysiology 
underlying WHIM syndrome and is sufficient to affect clinical outcomes. 
Mavorixafor and plerixafor share the same mechanism of action; however, mavorixafor is orally 
bioavailable and has a T1/2 suitable for once daily dosing (see Section 2.2.2.1). 
4.2.2. 
Rationale for the AMC Threshold 
The typical range of absolute monocyte count varies between both sex and age. AMC in patients 
between the ages of 12 and 18 usually ranges between 180 to 780 cells/µL and 190 to 
720 cells/µL in males and females, respectively. In adult patients (≥ 18 years of age), AMC 
typically ranges between 290 to 950 cells/µL and 250 to 840 cells/µL in males and females, 
respectively. 
Confidential
Page 1271

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 48 of 115 
4.2.3. 
Rationale for Study Structure 
This is the first clinical study of mavorixafor in patients with WHIM syndrome.  
Given the rarity of the disease under study as well as the known PK and PD profile of 
mavorixafor, a small number of patients (N=up to 15) are planned to be treated with mavorixafor 
on an open-label basis, with safety data reviewed on an approximately every 12-week basis by a 
DRC. Provision is made for dose escalation in individual patients, based on the AUCANC/ALC 
values to a maximum total daily dose of 400 mg (see Section 4.2.1). 
After at least 4 patients have completed the 24-week Treatment Period, the DRC will make 
recommendations regarding proceeding with a Phase 3 study. In addition, based on the 
experience in this study, a Phase 3 dose regimen for mavorixafor will be determined by the 
Sponsor with input from the DRC.  
4.2.4. 
Rationale for Mavorixafor Dosing Regimen 
Prior clinical studies demonstrated that mavorixafor is pharmacologically active at single doses 
of 50 mg (see Section 2.2.2.4). The hypersensitivity characteristic of the mutated CXCR4 in 
WHIM patients appeared to respond to relatively low doses of plerixafor (0.01 to 0.02 mg/kg 
compared with the label dose of 0.24 mg/kg). Based on these observations, the proposed clinical 
starting dose of mavorixafor in the initial Treatment Period was 50 mg QD orally. This starting 
dose was supported by the normal healthy male volunteer study (A5191). In this study, a single 
50 mg dose of mavorixafor showed a 1.3-fold increase in total WBC count; single doses of 
100 mg and 200 mg resulted in an increased total WBC count of up to 1.5- to 1.8-fold. The 
concentrations of mavorixafor at 24 hours after a single dose of 50 mg QD and 200 mg QD 
ranged between approximately 1 ng/mL and 9 ng/mL, respectively.   
The starting dose level of mavorixafor in the initial 2 patients was 50 mg QD. In both adults and 
adolescents, the predicted steady-state exposure for X4P 001 at 50 mg once daily was 
~235 ng•hr/mL. This exposure represents a ~144-fold margin relative to the exposures associated 
with microscopic multifocal necrosis in the 13-week dog study (AUC0-24hr: 33,822 ng•hr/mL) 
and a ~42-fold margin relative to the exposure at 10 mg/kg/day (AUC0-24 of 9935 ng•hr/mL) 
based on the NOAEL dose in 13-week dog study is <10 mg/kg/day.  
For additional subjects in this study, the starting dose of mavorixafor will be increased to 100 mg 
QD (see Section 2.4) or to a higher dose if emerging data (safety, PK, and PD) suggests that 100 
mg QD is a suboptimal dose (i.e., not achieving the objective of consistent ANC/ALC target 
thresholds). In addition, if emerging data suggests that QD regimen is not sufficient, BID dose 
regimen may be explored. The maximum total daily dose will not exceed 400 mg daily. 
4.2.5. 
Rationale for Mavorixafor Duration of Treatment 
Patients will receive treatment for at least 24 weeks. This treatment duration was selected based 
on the results of a proof-of-concept study conducted by the NIH [McDermott 2014], in which 3 
patients with WHIM syndrome were treated with plerixafor for 24 weeks (see Section 2.1.1 for 
Confidential
Page 1272

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 49 of 115 
details). Over that period, there was evidence of efficacy, with a durable increase in circulating 
leukocytes in all patients, associated with a decrease in the rate of infections and improved 
response in generalized warts following localized treatment with imiquimod [McDermott 2014]. 
The latter suggests improved immune function, with induction of an effective systemic anti-HPV 
response. Of note, these patients also demonstrated improved bone marrow histology, with 
decreases both in hypercellularity and in the frequency of hypermature, apoptotic neutrophils.  
Taken together, these changes support the hypothesis that CXCR4 antagonism reverses the 
primary pathophysiology underlying WHIM syndrome, i.e., hyperactive CXCR4 response to 
physiologic levels of its ligand CXCL12.  
The treatment duration of at least 24 weeks in the WHIM study is supported by the oncology 
clinical safety experience with mavorixafor to date.  As of March 13, 2017, 6 patients in the 
oncology program have been treated with mavorixafor (at doses of 400 mg QD or greater) for 
4-29 weeks. Three of the 6 patients have been on the treatment for approximately 6 months and 
treatment with mavorixafor is considered to be generally safe and well tolerated. 
Patients may continue to receive treatment with mavorixafor in an Extension Phase, if regionally 
applicable. The first 2 patients’ starting dose of 50 mg QD (see Section 2.2.3) and maximum 
dose of 150 mg QD was determined to be suboptimal. At the discretion of the Sponsor and with 
agreement from the investigator(s), these patients may have their dose escalated and have 
additional in-residence or dense-sampling visits conducted during the Extension Phase. 
Additional in-resident or dense-sampling visits may also be conducted in the absence of dose 
escalation in order to collect additional data regarding a specific dose.   
4.3. 
Endpoints 
4.3.1. 
Primary Endpoint 
The primary endpoint of this study is the mean value of the AUCANC and/or AUCALC collected 
over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated patients 
over 6 months. The ANC clinically meaningful threshold is defined as ANC ≥600/µL and the 
ALC clinically meaningful threshold is defined as ≥1000/µL. 
4.3.2. 
Exploratory Endpoints 
• Time above threshold (TAT) of ANC, ALC, and AMC at different dose levels of 
mavorixafor, where: 
• Time above threshold for ANC (TATANC) is the time in hours over 24 hours 
during which the ANC is maintained above 500 cells/μL. 
• Time above threshold for ALC (TATALC) is the time in hours over 24 hours 
during which the ALC is maintained above 1000 cells/μL.  
Confidential
Page 1273

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 50 of 115 
• Time above threshold for monocytes (TATmono) is the time in hours over 24 hours 
during which the monocytes count is maintained above the lower limit of normal 
corrected for age and sex per laboratory normal ranges. 
• Frequency and severity of infections, with diagnosis based on Investigator’s clinical 
assessment and severity assessed as Grade 1 to 4 using National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE). 
• Number of warts – applicable only to patients with cutaneous warts at baseline, and 
comparing number at baseline to number at end of Treatment Period.  
• Severity of genital warts – applicable only to patients with genital warts at baseline, and 
comparing number of lesions, size of largest lesion, and patient-reported morbidity at 
baseline to end of Treatment Period.  
• Antibody levels following revaccination – applicable only to patients who were (a) 
previously administered approved vaccines, (b) found at baseline to have predefined 
sub-protective levels of antibody, and (c) agree to repeat administration of the vaccine 
after at least 12 weeks of treatment. 
• Frequency of events requiring rescue therapy (G-CSF and/or Ig). 
• Rate of infections. 
• Rate of hospitalization events as compared to baseline. 
• Circulating WBCs: 
- Absolute and fold change from baseline and in total WBC counts, and in absolute 
numbers of lymphocytes, neutrophils, monocytes, and lymphocyte subpopulations 
cells.  
- Correlation of WBC, ANC, ALC, and AMC levels with plasma drug levels.  
• Ig and specific antibodies: 
- Changes from baseline in levels of total IgG, IgG subclasses, IgA, IgD, IgE and IgM. 
• Optional bone marrow aspirates (analyzed centrally by a blinded reviewer): 
- Change from baseline in cellularity. 
- Change from baseline in frequency of apoptotic cells. 
• 
Quality of life as assessed by the 36-item Short Form Survey, Life Quality Index, and 
HPV Impact Profile (if applicable), 
• Qualitative patient interviews conducted in the Extension Phase via telephone by a third 
party (optional) (see Section 7.1.5.3). 
Confidential
Page 1274

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 51 of 115 
5. 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1. 
Inclusion Criteria 
Patients with a clinical diagnosis of WHIM syndrome must meet all of the following criteria to 
be eligible for study participation: 
1. Be at least 18 years of age. 
2. Has signed the current approved informed consent form.  
3. Has a genotype-confirmed mutation of CXCR4. 
4. Agree to use contraception as follows: 
• For women of childbearing potential (WOCBP), agree to use highly effective 
contraceptive methods from Screening, through the study, and for at least 4 weeks 
after the last dose of study drug (see Section 7.4.1.1 for the definition of non-
childbearing potential). 
• For males, agree to use a condom with any WOCBP sexual partner from Day 1 of 
study treatment, through the study, and at least 4 weeks after the last dose of study 
drug. 
5. Be willing and able to comply with this protocol. 
6. Has confirmed ANC ≤400/µL or ALC ≤650/µL or both, where confirmation applies to 
each cell type separately and requires meeting the criterion on at least 2 independent 
blood samples collected over up to 14 days. 
5.2. 
Exclusion Criteria 
Patients with any of the following will be excluded from participation in the study: 
1. Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive 
ingredients.  
2. Is pregnant or breastfeeding. 
3. Has a known history of a positive serology or viral load for HIV or a known history of 
AIDS.  
4. Has, at Screening, laboratory tests meeting one or more of the following criteria: 
- A positive antibody test for hepatitis C virus, unless documented to have no 
detectable viral load on two independent samples.  
- A positive test for hepatitis B surface antigen. 
5. Has, at Screening, safety laboratory tests meeting one or more of the following criteria: 
- Hemoglobin <8.0 g/dL. 
- Platelets <75,000/μL.  
Confidential
Page 1275

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 52 of 115 
- Creatinine >2.0 x the ULN. 
- Serum aspartate transaminase (AST) >2.5x ULN. 
- Serum ALT >2.5x ULN.  
- Total bilirubin >1.5x ULN (unless due to Gilbert’s Syndrome, total bilirubin 
> 3.0x ULN and direct bilirubin > 1.5x ULN). 
6. Has, within 2 months prior to Day 1, received Plerixafor (open-label or blinded) as 
treatment of WHIM Syndrome. 
7. Has, within the 4 weeks prior to Day 1, had surgery requiring general anesthesia.  
8. Has, within 2 weeks prior to Day 1, received any of the following treatments:  
- G-CSF or granulocyte macrophage-colony stimulating factor (GM-CSF). 
- Immunoglobulin – Intravenous or subcutaneous (unless deemed necessary by the 
treating physician and after agreement from the Sponsor).  
- Corticosteroids (>10 mg prednisone equivalent per day). 
- Investigational therapies should be discussed with the Medical Monitor. 
9. Is currently taking or has, within 2 weeks prior to Day 1, received any medication that is 
a strong inhibitor or inducer of cytochrome P450 (CYP) and/or P-glycoprotein (see 
Sections 7.4.1.3 and 7.4.1.4).  
10. Has, at the planned initiation of study drug, an uncontrolled and active infection 
(excluding warts) that has the potential to raise the ANC counts.  
11. Has any other medical or personal condition that, in the opinion of the Investigator, may 
potentially compromise the safety or compliance of the patient, or may preclude the 
patient’s successful completion of the clinical study.  
Patients taking medications prohibited on the basis of CYP interactions (see Section 7.4.1.3), 
may, after discussion with the prescribing physician, be changed to a functionally equivalent, 
non-prohibited medication, and, after at least 2 weeks off the prohibited medication, reassessed 
for enrollment, including rescreening, if necessary.  
5.3. 
Strategies for Recruitment and Retention 
Following receipt of IRB/IEC approval, the Investigator may initiate patient recruitment (see 
Section 13.2). To reach an economically and socially diverse population, the study may be 
announced publicly, including on relevant Internet websites; prior to use, the form and content of 
such announcements will be submitted to the IRB/IEC for approval (see Section 13.2). 
Confidential
Page 1276

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 53 of 115 
5.4. 
Participant Withdrawal or Termination 
5.4.1. 
Reasons for Withdrawal or Termination 
To provide for consistent accounting of patient disposition, when study treatment is discontinued 
in an individual patient for any reason, the Investigator will complete the appropriate electronic 
case report form (eCRF) and select the primary reason from the following standard categories:  
• Treatment-limiting toxicity (TLT) event – as defined in Section 5.7.  
• Completion – Completed 24 weeks of treatment and End-of-Treatment (EOT) and 
End-of-Study (EOS) visit procedures (Week 25 [or at the time of study drug 
discontinuation] and 30 ±5 days after the last study drug dose, respectively).  
• Adverse Event, other than TLT – This includes any AE (clinical or laboratory; serious or 
non-serious; regardless of relation to study drug), that represents the reason study drug 
was discontinued, including:  
- The medical judgment of the Investigator based on the best interests of the 
patient.  
- The patient’s request, based on any AE.  
• Lost to Follow-Up – The patient stopped coming for visits.  
• Study Termination – by the Sponsor, for any reason.  
5.4.2. 
Handling of Participant Withdrawals or Termination 
When study treatment is discontinued for any reason, the EOT and EOS visits will be performed 
as specified (see Section 7). If a patient cannot be seen, attempts will be made to contact the 
patient by telephone to inquire about reasons for stopping participation and get updated 
information on any unresolved AEs.  
5.5. 
Premature Termination or Suspension of Study 
The Sponsor reserves the right to discontinue or suspend the study for safety or administrative 
reasons at any time, at an individual site or overall in accordance with local laws and regulations. 
Should the study be terminated and/or the site closed for whatever reason, all study 
documentation must be archived and study drug must be destroyed according to local policy or 
returned to the Sponsor or its representative per Sponsor’s instructions. 
If the study is terminated prematurely or suspended, the Sponsor will promptly inform the 
participating Investigators and institutions, the regulatory authorities, and the IRB/IEC (see 
Section 13.2 for definition) of the termination or suspension and the reason(s) for the action. 
Confidential
Page 1277

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 54 of 115 
5.6. 
Patient Restrictions during the Conduct of the Study  
In the interest of their safety and to facilitate assessment of both safety and treatment effect, the 
patients participating in this study will be requested to agree to the following restrictions during 
the study:  
• Not start any new prescription medications, except as prescribed or approved by their 
Investigator or if required in an emergency. 
• Not take any over-the-counter medications, except as instructed or approved by their 
Investigator.  
• Not drink grapefruit juice or eat grapefruit.  
5.7. 
Definition of Treatment-Limiting Toxicity 
A TLT event for mavorixafor is defined as an AE that meets both of the following criteria:  
a) Is assessed by the Investigator as possibly or probably related to mavorixafor 
(see Section 8.2.3).  
b) Represents one of the following events (grading as defined by the NCI CTCAE, v4.03) (see 
Section 8.2.1):  
• Is a Grade 3 or Grade 4 clinical event. 
- Exception: Grade 3 nausea, vomiting, or diarrhea lasting <48 hrs in patients who 
have received suboptimal medical management 
• Is a confirmed Grade 3 or Grade 4 laboratory event. 
- Exception: Grade 3 electrolyte abnormalities that persist <72 hrs and do not 
require hospitalization.  
- Exception: Grade 3 AST/ALT increases that persist <5 days and with total 
bilirubin ≤1.5x ULN. 
• Is one of the following, which are designated as critical TLT events: 
- AST/ALT increased >3x ULN (Grade 2) with total bilirubin increased >2x ULN 
in the absence of cholestasis.  
- Retinopathy – confirmed treatment-emergent retinopathy.  
- Platelets <50,000/mm3 (Grade 3) with bleeding or <25,000/mm3 (Grade 4). 
5.8. 
Duration of Treatment 
Patients are expected to receive treatment for 24 weeks in the initial Treatment Period or until the 
earliest of: 
• TLT event – see Section 5.7. 
Confidential
Page 1278

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 55 of 115 
- For any TLT event occurring during the first 4 weeks of treatment, study 
treatment will be discontinued permanently.  
- For one of the critical TLT events (see Section 5.7) occurring after successful 
completion of 4 weeks of treatment, study treatment will be discontinued 
permanently. 
Extension Phase (if applicable): Patients may continue participation in an open-label extension 
phase of the protocol and receive treatment with mavorixafor, with an adjusted schedule of 
assessments (see Section 7.3.1 for details). The first 2 patients’ starting dose of 50 mg QD (see 
Section 2.2.3) and maximum dose of 150 mg QD was determined to be suboptimal. At the 
discretion of the Sponsor and with agreement from the Investigator(s) and Data Monitoring 
Committee, these patients may have their dose escalated and have additional in-residence or 
dense-sampling visits conducted during the Extension Phase. Additional in-resident or dense-
sampling visits may also be conducted in the absence of dose escalation in order to collect 
additional data regarding a specific dose.   
When study treatment is discontinued for any reason, the EOT and EOS visits will be performed 
as specified (see Table 1-1). If a patient cannot be seen, attempts will be made to contact the 
patient by telephone to inquire about reasons for stopping participation and get updated 
information on any unresolved AEs.  
5.9. 
Number of Patients  
The maximum exposures to mavorixafor, the investigational agent in this study, will be as 
follows:  
• Maximum number of patients:  
- Initial Treatment Period and Extension Phase: Up to 15 adult patients (≥18 years 
of age). 
• Maximum treatment duration:  
- Initial Treatment Period: Up to 24 weeks. 
- Extension Phase: Until commercial availability (if regionally applicable) or 
termination of study by Sponsor for any reason. 
5.10. Treatment Assignment 
In the initial Treatment Period and Extension Phase, all patients will be treated with mavorixafor 
on an open-label basis. 
Confidential
Page 1279

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 56 of 115 
6. 
STUDY DRUG(S) 
6.1. 
Study Drug(s) and Control Description 
6.1.1. 
Acquisition 
All study drug will be supplied by the Sponsor. 
6.1.2. 
Formulation, Appearance, Packaging, and Labeling 
All manufacture, packaging and labeling operations will be performed according to International 
Conference on Harmonisation (ICH) Good Manufacturing Practice (GMP) and Good Clinical 
Practice (GCP) guidelines.  
Table 9: 
Physical and Chemical Properties of Active Ingredient (Drug Substance) 
Name 
Mavorixafor (X4P-001) 
Drug Class 
Chemokine (C-X-C motif) receptor 4 (CXCR4) antagonist 
INN 
Not Assigned 
Molecular Formula 
C21H27N5 
Molecular Weight 
349.48 amu 
Appearance 
white to pale yellow solid 
Solubility 
Mavorixafor is freely soluble in the pH range 1.0 to 8.0 (>100 mg/mL), sparingly soluble at pH 9.0 
(10.7 mg/mL) and slightly soluble at pH 10.0 (2.0 mg/mL). Mavorixafor is only slightly soluble in 
water.  
Melting Point 
111.4 °C 
Table 10: 
Formulation of Mavorixafor 100 mg Capsule 
Name 
Mavorixafor 100 mg Capsule 
Active ingredient 
Mavorixafor (X4P-001) 
Excipients 
Microcrystalline cellulose, dibasic calcium phosphate dihydrate, croscarmellose sodium, sodium 
stearyl fumarate, colloidal silicon dioxide, sodium lauryl sulfate 
How supplied 
Dispensing instructions will be provided in the Pharmacy Manual 
Storage 
5°C ± 3°C; Protect from light and humidity 
Administration 
Oral 
6.1.3. 
Product Storage  
For product storage details, see Table 10. 
6.1.4. 
Preparation 
None. 
6.1.5. 
Dosing and Administration 
All patients will receive mavorixafor capsules (100 mg dose strength). 
Confidential
Page 1280

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 57 of 115 
Patients will be instructed about both dosing schedule and requirements relating to food or drink 
near the time of dosing.  
The first dose of study drug will be taken at the study center under the observation of study 
center personnel. Patients will be observed for at least 1-hour post-dose. 
Dosing Schedule. It is expected that the daily dose will be taken as follows: 
• Dosing should be at a consistent time each morning (± 2 hr). 
• The interval between successive doses should not be <21 hours nor >27 hours. If the 
interval would be <16 hrs before the next scheduled dose time, the dose should be 
omitted and the usual schedule resumed at the next dose. 
If there are any repeated compliance issues related to the study drug, the study team, and Medical 
Monitor must be consulted. 
Restrictions relating to food. Absorption is impacted by food and patients will be instructed as 
follows:  
• No food or drink (except water) for 1-hour pre-dose 
• No food or drink (except water) for 2-hours post-dose. 
Patients for whom the scheduling requirements and eating restrictions represent significant 
difficulties should be discussed with the Medical Monitor to develop the most effective regimen 
possible.  
In the Extension Phase, all patients will receive mavorixafor; the dose will not exceed 400 mg 
daily. Dose-escalation may be continued during the Extension Period, if necessary, after prior 
approval from the Data Monitoring Committee, based on AUCANC/ALC values, safety data, and 
review of clinical efficacy, up to a maximum dose of 400 mg daily. 
6.1.6. 
Route of Administration 
All study drug will be administered orally. 
6.1.7. 
Starting Dose and Dose Escalation Schedule 
In the initial Treatment Period, 2 patients were treated at the initial proposed starting dose of 
50 mg QD; this dose was determined to be a suboptimal dose. All subsequent patients received 
mavorixafor at a starting dose of 100 mg QD or a higher dose with potential escalation based on 
AUCANC/ALC values to a maximum total daily dose of 400 mg. Provision is made for dose 
interruption and discontinuation (see Section 6.1.8).  
6.1.8. 
Dose Adjustments/Modifications/Delays 
If a patient receiving mavorixafor successfully completes the first 4 weeks of treatment, and 
subsequently has a TLT event (other than those designated critical) (see Section 5.7), study 
Confidential
Page 1281

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 58 of 115 
treatment may, with the agreement of the patient, the Investigator, and the Medical Monitor, be 
managed as follows: 
• Mavorixafor will be held (dosing interrupted).  
• If the event does not improve to Grade ≤1 within the next 14 days, mavorixafor will be 
discontinued.  
• If the event improves to Grade ≤1 within 14 days of holding mavorixafor, the patient may 
resume mavorixafor at the same dose. 
• If there are any further Grade >2 recurrences, study treatment will be discontinued.  
• If patients are escalated to 400 mg QD and dose interruptions are required for AEs they 
may have their dose reduced to 300 mg QD at the discretion of the investigator. 
If dosing is interrupted for an extended period, the study treatment may be discontinued.  
6.1.9. 
Duration of Therapy 
Patients are expected to receive treatment for 24 weeks in the initial Treatment Period or until 
development of a TLT (see Section 5.7). 
6.1.10. 
Treatment Compliance 
Treatment compliance will be monitored by 2 procedures. 
• Patients will complete a daily diary to record the number of capsules taken. Diaries will 
be reviewed with the patient at each clinic visit.  
• Mavorixafor will be dispensed in bottles, which will be examined visually at each clinic 
visit; non-destructive pill counts will be performed if indicated. 
6.2. 
Study Drug Accountability Procedures 
Mavorixafor will be provided by the Sponsor. The Investigator at each study site is responsible 
for the control of study drug, and will identify trained and experienced personnel to handle it in 
accordance with the protocol and appropriate GCP and GMP principles. This includes:  
• Storing the drug in a secure, controlled-access location. 
• Storing the drug under the specified conditions, including daily monitoring and recording 
of storage temperature. 
• Maintaining records of the receipt of study drug and providing acknowledgement of 
receipt. 
• Dispensing and administering study drug only in accordance with the protocol. 
• Maintaining drug accountability records indicating the disposition of study drug, 
including a Drug Dispensing Log containing the following information: 
Confidential
Page 1282

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 59 of 115 
- Identification of the patient to whom the study drug was dispensed. 
- Date(s) and quantity of the study drug dispensed to the patient.  
- Date(s) and quantity of the study drug returned by the patient at each study visit. 
• Having all records and drug supplies available for inspection by the study monitor.  
6.3. 
Disposition of Study Drug 
At the completion of the study, the site must obtain written authorization from the Sponsor 
regarding the final disposition of any remaining mavorixafor; that disposition must be 
appropriately documented. Typical procedures for handling any remaining study drug include the 
following: 
• Returning study drug to the Sponsor.  
• Destroying study drug at the study site according to the site’s institutional standard 
operating procedure. 
Confidential
Page 1283

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 60 of 115 
7. 
STUDY PROCEDURES AND SCHEDULE 
7.1. 
Study Procedures/Evaluations 
All patients must provide written informed consent (or assent with parental/legal guardian 
consent) and the consent procedure recorded in the source documentation before the performance 
of any study-related procedures. 
7.1.1. 
Baseline and Safety Assessments 
7.1.1.1. 
Enrollment Procedure 
Patients assessed by the Investigator as eligible after completing Screening will have all 
screening data entered into a web-based Electronic Data Capture (EDC) system. The data will be 
reviewed by the Medical Monitor or designated study personnel and any questions discussed 
with the site.  
After acceptance, the Investigator and site pharmacy will be provided in writing (by email and/or 
fax) formal acknowledgement that the patient may initiate treatment as per protocol.  
7.1.1.2. 
Genotyping 
A blood sample will be collected during Screening and submitted to the central laboratory for 
sequencing of CXCR4. Patients are required to have a genotype-confirmed mutation of CXCR4 
consistent with WHIM syndrome to be eligible for the study. 
7.1.1.3. 
Bone Marrow Aspiration (Optional) 
For patients who provide explicit written informed consent (or assent with parental/legal 
guardian consent), bone marrow aspiration will be performed during Screening and at the EOT 
visit. This procedure is optional; agreement to this procedure is not required for study entry. 
At Screening, patients must be off all treatment for WHIM for the intervals specified in 
Exclusion #5.  
Smears will be graded in batches for cellularity and myelokathexis by a blinded 
hematopathologist. If sufficient material is available, samples will be analyzed for markers of 
neutrophil apoptosis and lymphocyte subpopulations. 
7.1.1.4. 
Revaccination 
At Week 12 in the initial Treatment Period, patients that have levels of antibody below 
pre-defined protective levels will be revaccinated with common childhood vaccines. Blood 
samples will be collected from patients after revaccination for assessment of total IgG, IgG 
subclasses, IgA, IgD, IgE and IgM, and for levels of selected specific antibodies to common 
vaccine antigens in serum.  
During the Extension Phase, patients who have inadequate antibody responses to tetanus toxoid 
or HPV vaccine will be revaccinated one time with tetanus, diphtheria, and pertussis (TDaP) and 
Confidential
Page 1284

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 61 of 115 
HPV 9-valent vaccine, recombinant (Gardasil®9). The vaccination regimen for Gardasil 9 will 
follow current recommendations from Centers for Disease Control for unvaccinated individuals 
(e.g., 3 doses at months 0, 2, and 6 for patients greater than age 14) and may be given to older 
patients regardless of age. Patients may receive doses of Gardasil 9 at their local physician's 
office provided details are transmitted to the investigator and recorded in source documentation. 
In the Extension Phase, patients with antibody levels below pre-defined protective levels will be 
revaccinated at the 6-month visits. 
7.1.1.5. 
Vital Signs 
Vital signs include heart rate, blood pressure (BP) and temperature. Where feasible, vital signs 
should be measured before blood is drawn and after the patient has been sitting or semi-reclined 
quietly for 5 minutes with the BP cuff in place on the non-dominant arm. BP and heart rate 
measurements may be done manually or by automated recorder. Temperature will be obtained 
using an electronic (rapid reading) device.  
Vital sign measurements will be assessed by the Investigator as either ‘normal’, ‘abnormal, not 
clinically significant’, or ‘abnormal, clinically significant’. Clinically significant abnormal vital 
sign measurements will be reported as an AE, and, if possible, should be repeated at clinically 
relevant intervals until resolved or stabilized.  
7.1.1.6. 
Physical Examination and Body Weight 
Complete physical examinations will include measurement of body weight and height, and 
examination of general appearance, skin, neck (including thyroid), eyes, nose, throat, heart, 
lungs, abdomen, lymph nodes, extremities, and nervous system.  
Examination of the reproductive system will be performed if genital warts are reported by history 
or are reported as present at the time of the physical examination; or if symptoms or AEs related 
to the reproductive system are reported. The examination may be performed by the Investigator 
or delegated to a specialist. 
Physical examination findings will be assessed by the Investigator as either ‘normal’, ‘abnormal, 
not clinically significant’, or ‘abnormal, clinically significant’. Any clinically significant changes 
identified after the Baseline (Screening) examination will be recorded as AEs (see Section 8). 
7.1.1.7. 
Assessment of Warts 
Warts on the hands and feet will be identified during Screening and at all scheduled visits. 
Lesions will be assessed by counting the number of warts on the hands and feet. Genital warts 
will be assessed by reported physician examination and patient-reported outcome of impact on 
psychosocial well-being.  
Areas with warts identified during Screening will be monitored throughout the study; areas that 
develop new warts during the study will be monitored for the remainder of the study according to 
the time and events schedule. 
Confidential
Page 1285

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 62 of 115 
Photographs of representative warts may be collected. 
7.1.1.8. 
Ophthalmologic Examination 
Ophthalmologic examination will be performed as scheduled and include the following 
elements: assessment of visual acuity (using Snellen examination), refraction, assessment of 
color vision, slit lamp examination, and retinal examination with photographs. All examination 
reports and photographs will be submitted to a central repository as soon as feasible after being 
performed to be reviewed for quality and completeness. 
Retinal abnormalities noted at Screening will be discussed with the Medical Monitor. 
Examination by a second ophthalmologist may be requested to confirm the description of the 
findings and the adequacy of the photographs. Enrollment may proceed with the approval of the 
Medical Monitor.  
Any patient reported to have treatment-emergent findings of retinopathy will be examined by a 
second ophthalmologist. 
All examination reports and photographs may be reviewed by an independent, blinded 
ophthalmologist designated by the Sponsor.  
7.1.1.9. 
Electrocardiogram (ECG) 
Standard 12-lead ECG will be obtained after the patient has been semi-recumbent for ~10 
minutes. The following ECG parameters will be recorded: ventricular rate, RR interval, PR 
interval, QRS interval, QT interval, QTc interval, and QTc method using Fridericia's formula: 
QTc = QT/RR1/3.  
7.1.2. 
Pharmacokinetic Assessments 
For all patients receiving study drug, dense PK samples will be obtained during the 24-hour 
periods in-residence at the following time points: 
• Time 0 (up to 15 minutes prior), 30 minutes, 60 minutes (each ±5 minutes) and 
90 minutes, 2, 3, and 4 hours (each ±15 minutes), and 8, 12, 16, and 24 hours (each 
±30 minutes). 
Additional time point 0 samples (trough) will be collected at Day 1 and Weeks 9, 17 and 25.   
Blood samples for plasma levels of mavorixafor will be analyzed for mavorixafor concentration 
using reversed-phase high performance liquid chromatography with tandem mass spectrometry 
detection.  
PK data will be analyzed using descriptive statistics for AUC, Cmax, and Tmax by patient and 
dosage regimen over the preceding week (initial Treatment Period only).  
In the Extension Phase, trough PK samples will be obtained at the 12-month visits; dense PK 
sampling will be optional. In addition, a single sample will be obtained for evaluation of 
Confidential
Page 1286

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 63 of 115 
mavorixafor metabolites at the yearly visit (e.g., Month 12, 24, etc.), whichever occurs earliest 
for each patient after implementation of the v5.0 protocol amendment. 
7.1.3. 
Biomarker Assessments (in PBMC) 
Biomarker samples will be collected concurrent with time point 0 PK samples. Assessments may 
include samples analyzed by flow cytometry for subpopulations of peripheral blood mononuclear 
cells (PBMC). Candidate subsets are shown in Table 11.  
Table 11: 
Candidate Subsets of Peripheral Blood Mononuclear Cells for Biomarker 
Analysis 
Naïve T cells 
Memory T cells 
B cells 
Transitional B cells 
NK cells 
Monocytes 
 
 
Abbreviations: NK=natural killer. 
These investigational assays will be performed by a central laboratory designated by the 
Sponsor; to maximize consistency, tests may be batched. For patients who consent to future 
research, a subset of PBMCs may be isolated, frozen, and stored for future research to better 
understand the leukocyte defect in patients with WHIM and the immune response to 
mavorixafor. The clinical significance of these tests is unknown at this time, and the results will 
not be assessed by the Investigator.  
Detailed procedures for the collection, processing, storage, and shipment of these samples will be 
provided in the Laboratory Manual.  
7.1.4. 
Efficacy Assessments 
7.1.4.1. 
WBC, ANC, ALC, and AMC for Calculation of TAT and 24-hour AUCANC and AUCALC 
Patients are scheduled to be admitted to a research unit 3 times over each 24-week Treatment 
Period (Weeks 5, 13, and 21) and blood samples collected as follows: 
• Time 0 (up to 15 minutes prior), 30 minutes, 60 minutes (each ±5 minutes), and 
90 minutes, 2, 3, and 4 hours (each ±15 minutes), and 8, 12, 16, and 24 hours (each 
±30 minutes). 
Time point 0 represents time of oral dosing that morning (typically between 7 and 8 am), the 
sample will be drawn pre-dose. 
The in-residence stays will be rescheduled in the event of recent infection, administration of 
antibiotics, or of rescue therapy with G-CSF or Ig prescribed for an acute infection. Patients 
should be free from active infections and washed-out from any rescue therapies (G-CSF, Ig, 
corticosteroids, epinephrine, or any other treatment that in the opinion of the investigator might 
Confidential
Page 1287

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 64 of 115 
impact cell counts) for a period of at least two weeks before obtaining the first blood samples 
during an in-residence stay (provision is made for patients on prophylactic long-term Ig after 
initial approval from the Medical Monitor). 
Whole blood samples will be sent to a central laboratory selected by the Sponsor, and WBC, 
ANC, ALC, and AMC will be determined by standard methods. The 24-hour AUCs will be 
calculated as detailed in Section 10.4.2. 
The 24-hour AUCANC and AUCALC represent the primary assessment for determining dose 
escalation. 
7.1.4.2. 
Antibodies and Immunoglobulins in Revaccinated Patients 
Serum will be collected at Screening and analyzed for levels of total IgG, IgG subclasses, IgA, 
IgD, IgE and IgM, and for levels of specific antibodies to common vaccine antigens (Table 12). 
Samples will be collected subsequently to permit monitoring of patients with depressed Ig levels 
or sub-protective levels of specific antibodies.  
Table 12: 
Common Vaccines That Elicit Protective Antibody by Age Range of Initial 
Administration 
Birth to 6 years (bacteria) 
Birth to 6 years (viruses) 
Age 7 to 18 years 
Tetanus toxoid 
H. influenzae type B polysaccharide 
Measles, Rubella 
Human papilloma virus 
7.1.4.3. 
Research Blood 
For patients who consent to future research, a subset of PBMCs may be isolated, frozen, and 
stored for future research to better understand the leukocyte defect in patients with WHIM and 
the immune response to mavorixafor. Additionally, any duplicate and unused stored blood or 
serum samples may be used for future research to better understand the effect of treatment on the 
immune response of patients with WHIM syndrome. 
7.1.5. 
Assessments of Clinical Benefit 
7.1.5.1. 
Investigator-reported Data 
In the initial Treatment Period, investigators will report the following items via an EDC system: 
• All concomitant medications, including antibiotics, as well as rescue therapies (e.g., 
G-CSF, Ig).  
• Clinical diagnoses of infection, including supporting laboratory data and sufficient 
information to support CTCAE severity grading.  
• Assessment of Warts 
- Number of warts will be assessed on the top and bottom of both hands and feet. 
Confidential
Page 1288

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 65 of 115 
- Genital warts will be assessed by physician examination with description of the 
number of lesions and size of the largest lesion. 
Photographs may be taken of selected warts. 
In the Extension Phase, the investigator will continue to evaluate warts as in the initial Treatment 
Period.  
7.1.5.2. 
Patient-reported Data  
Prospective patient-reported data will be collected daily by automated telephone- or web-based 
system. These data will include: 
• Daily monitoring of temperature. 
• Participation in activities of daily living (e.g., work, school, household tasks). 
• Unscheduled healthcare visits, including hospitalizations, for signs or symptoms of 
infection. 
• Treatment for infection, including antibiotics. 
• Unscheduled hospitalizations for other reasons. 
Patients will complete validated Quality of Life Questionnaires (36-item Short Form Survey 
[SF-36] and Life Quality Index [LQI], and HPV Impact Profile [if applicable]) per schedule of 
events (see Appendix 18.2 and Appendix 18.3 for further details regarding these assessments). 
7.1.5.3. 
Qualitative Patient Interview 
All patients on the Extension Phase may be invited to participate in a patient interview conducted 
by an independent third party. The patient interview may be conducted via telephone at any point 
during the Extension Phase. The interviews will follow a Semi-Structured Interview Guide.  
The purpose of the patient interview is to capture, directly from the patient, if they experienced a 
meaningful improvement from baseline. Specifically, the participants may be interviewed about 
their decision to enter the clinical study, the patient’s expectations about a meaningful 
improvement in their condition, the changes they experienced during the clinical study, and their 
perception as to why they did or did not experience a meaningful improvement in their condition. 
Informed consent will be documented prior to the interview. Interviews will be audio recorded 
unless the participant refuses to be audio recorded, in which case interviewer notes will serve as 
the source data for analysis. Subsequent transcripts will be generated from the interviews and 
translated into English for analysis, if needed. Qualitative data will be coded using ATLAS.ti 
software, which was designed for the systematic qualitative analysis of textual, graphical, audio, 
and vignette data. A qualitative coding dictionary will be developed for use in the analyses.  
Any potential AEs reported during the interviews will be communicated to the Investigator for 
follow-up and documentation. 
Confidential
Page 1289

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 66 of 115 
7.2. 
Laboratory Procedures/Evaluations 
7.2.1. 
Clinical Laboratory Evaluations 
7.2.1.1. 
Safety Laboratory Studies 
The laboratory safety tests below will be performed as scheduled by a central laboratory facility. 
However, if the patient is not able to travel to the site for the schedule clinic visit due to 
extenuating circumstances, safety labs may be drawn and or processed by a local laboratory. The 
Investigator may order additional local laboratory tests consistent with their routine standard of 
care.  
Table 13: 
Safety Laboratory Tests  
Hematology Panel 
 
Hematocrit 
WBC differential and absolute cell counts: 
Hemoglobin 
Basophils 
Platelet count 
Eosinophils 
Red blood cell count 
Lymphocytes 
WBC count 
Monocytes 
 
Neutrophils 
Clinical Chemistry Panel 
 
Alanine aminotransferase 
Inorganic phosphorus  
Albumin 
Lactate dehydrogenase  
Alkaline phosphatase 
Lipase  
Amylase 
Magnesium 
Aspartate aminotransferase 
Potassium 
Bicarbonate 
Sodium 
Calcium 
Total bilirubin** 
Chloride 
Total protein 
Creatine kinase 
Urea  
Creatinine* 
Uric acid 
Glucose 
 
*Creatinine clearance will be calculated using the method of Cockcroft and Gault (Cockroft, Gault, 1976). 
** If the total bilirubin concentration is above 1.5 times the upper limit of normal, direct and indirect bilirubin should be 
differentiated. 
Pregnancy tests (WOCBP only) 
 
beta-human chorionic gonadotropin 
 
Follicle stimulating hormone 
 
Serologic tests (Screening only) 
 
HBsAg 
 
Antibody to HCV 
Abbreviations: HbsAg=hepatitis B virus surface antigen; HCV=hepatitis C virus; WBC=white blood cell; 
WOCBP=women of childbearing potential. 
Confidential
Page 1290

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 67 of 115 
7.2.1.2. 
Reporting of Safety Laboratory Tests 
Results of safety laboratory tests (except serology) are expected to be available to the 
Investigator within 48 hours. Procedures for the Investigator assessment of the results are 
detailed in Section 8.1.5. Procedures for the analysis of laboratory data are described in Section 
8.2.2.  
7.2.1.2.1. 
Pregnancy Testing 
All WOCBP will have a urine or serum pregnancy test done at the site at each office visit. 
Results must be obtained at the baseline visit prior to dosing on Day 1. A negative result is 
required to dispense study drug. The pregnancy test results will be maintained in the source 
documents.  
All WOCBP must notify the site if a menstrual cycle is missed. 
7.2.1.3. 
Repeating Abnormal Laboratory Tests 
Laboratory tests showing abnormal or exclusionary values at Screening may be repeated no more 
than once; however, exclusionary serologic results may not be repeated.  
After dosing, abnormal laboratory tests assessed as “clinically significant” values may be 
repeated as often as deemed clinically necessary by the Investigator until the test values are 
clinically acceptable or until an explanation other than drug effect is given.  
7.2.2. 
Other Assays or Procedures 
None. 
7.2.3. 
Specimen Preparation, Handling, and Storage 
Laboratory samples are to be prepared, handled, and stored as instructed in the laboratory 
manual. 
7.2.4. 
Specimen Shipment 
Laboratory samples are to be shipped as instructed in the laboratory manual. 
7.3. 
Study Schedule 
The schedule of events for the initial Treatment Period is in Table 1-1. A brief overview of the 
study schedule is as follows:  
• Genotyping and ANC and ALC for eligibility will be performed by a central laboratory to 
assure consistent data. See Table 1-1 for details regarding Screening assessments.  
• Alternative treatments (e.g., G-CSF, GM-CSF, Ig, plerixafor, antibiotics) will be 
discontinued, as indicated in the exclusion criteria, prior to receiving treatment (see 
Section 5.2). 
Confidential
Page 1291

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 68 of 115 
• Patients will be requested to consent explicitly to have optional bone marrow aspirates 
performed at Screening and the EOT visit. Agreement to these procedures will not be 
required for study entry.  
• All patients will be monitored with regularly scheduled office visits, daily remote 
monitoring, and 3 in-residence periods for 24-hour collections for WBC, ANC, ALC, 
AMC, and, in the Treatment Period, PK.  
• Patients with baseline antibody levels to standard vaccines that are below the levels 
recommended for protection will be offered the opportunity for repeat vaccination after at 
least 12 weeks’ treatment.  
• The EOT visit is scheduled for Week 24; the patient should continue taking study drug up 
to this visit. If treatment is terminated prematurely for any reason, the EOT visit will be 
performed as soon as possible after the decision to terminate. 
• The EOS visit will be performed 30 days ±5 days after the last dose of study drug.  
• Extension Phase (if regionally applicable): Patients may continue to receive treatment 
during an Extension Phase of the protocol (see Section 7.3.1 for details). Patients may be 
considered eligible for the Extension Phase after the EOT or EOS visit; informed consent 
will be completed before entry into the Extension Phase.  
Note: Home health visits are authorized if there are extenuating circumstances that 
would impede patients from coming to the study site for a scheduled visit. Requests 
for home health visits will be reviewed and approved by X4 on a case-by-case basis. 
Home health visits will be an option applicable for all study visits. 
7.3.1. 
Extension Phase 
The schedule of events for the Extension Phase is in Table 1-2. If regionally applicable, 
provision is made for patients who wish to continue participating in the study to continue 
receiving treatment with mavorixafor in an Extension Phase. With the agreement of the 
Investigator, patients will enter the Extension Phase of the study and receive study drug until it 
becomes available via an alternative mechanism (e.g., drug is commercially available, an 
expanded access program, etc.). At the discretion of the Sponsor and with agreement from the 
Investigator(s) and Data Monitoring Committee, patients may have their dose escalated and have 
additional in-residence or dense-sampling visits conducted during the Extension Phase. 
Additional in-resident or dense-sampling visits may also be conducted in the absence of dose 
escalation in order to collect additional data regarding a specific dose. The patient’s participation 
in the extension phase will be complete when study treatment is discontinued and all Extension 
Phase Visits are complete. 
The following procedures will apply during the Extension Phase:  
Confidential
Page 1292

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 69 of 115 
1. Patients will have on-site office visits for the assessment of vital signs, safety laboratory 
tests, and pregnancy tests between annual office visits, at 6-month (±30 days) intervals. 
2. Office visits every 12 months (±30 days), for standard safety assessments and the 
following (see Table 1-2 for the full Schedule of Events): 
• Assessment of warts 
• Ophthalmologic examination 
• Trough WBC, ANC, ALC, AMC, and PK sampling 
• ANC, ALC, and AMC sampling for TAT and AUC (optional) 
• PK dense sampling (optional) 
• Revaccination (see Section 7.1.1.4) 
• Serum Ig and specific antibodies 
• Biomarker sampling 
• Pharmacogenetic sampling and research blood draw (optional) 
• Quality of life questionnaires  
3. Full safety reporting requirements will apply, as detailed in Section 8.4. 
4. Follow-up for safety will be conducted as per routine standard of care. 
5. An optional patient interview via telephone may be conducted during the Extension 
Phase by an external third party (see Section 7.1.5.3). 
6. An EOS visit will be conducted 30 days ±5 days after the last dose of study drug. 
If a patient has their dose escalated during the Extension Phase, additional in-residence or 
dense-sampling visits may be conducted after the patient has received the escalated dose for at 
least 2 weeks.  
Additional optional in-resident or dense-sampling visits may also be conducted in the absence of 
dose escalation in order to collect additional data regarding a specific dose.  Patients may decline 
these additional visits and still continue treatment in the Extension Phase. 
7.4. 
Concomitant Medications, Treatments, and Procedures  
Prior treatments for WHIM syndrome will be recorded in the eCRF.  
Any concomitant medication used from time of screening through last study visit will be 
recorded in the eCRF, including dose, dosage regimen, and indication (reason for its 
prescription).  
Confidential
Page 1293

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 70 of 115 
7.4.1. 
Precautionary Medications, Treatments, and Procedures 
7.4.1.1. 
Non-childbearing Potential 
A WOCBP is defined as any female patient who is not postmenopausal or has not had a 
documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. A postmenopausal 
state is defined as no menses for 12 months without an alternative medical cause. A high follicle 
stimulating hormone level in the postmenopausal range may be used to confirm a post-
menopausal state in women not using hormonal contraception or hormonal replacement therapy. 
However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone 
measurement is insufficient, and patients will be required to use a highly effective method of 
contraception. Non-childbearing potential is defined as a female who meets either of the 
following criteria: Age ≥50 years and no menses for at least 1 year.  
7.4.1.2. 
Highly Effective Birth Control (Contraception) Methods 
A WOCBP must use a highly effective method of contraception from screening, during 
participation in the study, and through at least 4 weeks after the last dose of study drug. 
Acceptable methods include: 
• Systemic hormonal contraceptives when used with an additional barrier method 
(e.g., male condom): 
− Combined (estrogen and progesterone containing) hormonal contraception 
associated with inhibition of ovulation (either oral, intravaginal, or transdermal). 
− Progesterone-only hormonal contraception associated with inhibition of ovulation 
(either oral, injectable, or implantable). 
• Intrauterine device. 
• Intrauterine hormone-releasing system. 
• Bilateral tubal occlusion. 
• Vasectomized partner who has received a medical assessment of surgical success 
(when the partner is the sole partner). 
• Sexual abstinence (refraining from heterosexual intercourse during the entire period 
of risk associated with the study treatment). The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the clinical study and the preferred and 
usual lifestyle of the patient. 
• Double barrier methods of contraception are acceptable, such as condoms with 
spermicide. 
All WOCBP will undergo serum or urine pregnancy testing at every visit; a negative result is 
required to dispense study drug. WOCBP must notify the site if a menstrual cycle is missed. 
Patients who become pregnant will be discontinued from the study. 
Fertile males are required to use a male condom (with spermicide) with a sexual partner who is a 
WOCBP starting at screening, during participation in the study, and through 4 weeks after the 
last dose of study drug. 
Confidential
Page 1294

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 71 of 115 
7.4.1.3. 
Restrictions related to CYP Interactions 
Mavorixafor is metabolized through, and interacts with, the CYP metabolic enzymes found in 
the hepatic and intestinal microsomes (see Section 2.2.2.3 for details).  
Based on these observations, the following restrictions are placed on concomitant medications:  
• Strong inhibitors and inducers of CYP3A4 are prohibited.  
- In the event the Investigator and Medical Monitor conclude that a strong inhibitor 
“must be used”, the dose of mavorixafor will be modified as per Table 14: 
Table 14: 
Dose Modification of Mavorixafor when Co-Administered with a 
Strong CYP3A4 Inhibitor 
Current Dose 
Reduced Dose 
400 mg QD 
300 mg QD 
300 mg QD 
200 mg QD 
200 mg QD 
100 mg QD 
100 mg QD 
Treatment Discontinued 
Abbreviations: QD=once daily. 
• Grapefruit juice, a variable inhibitor of CYP3A4, is prohibited.  
• Moderate inhibitors and inducers of CYP3A4 are to be prescribed only with the approval 
of the Medical Monitor; additional monitoring of mavorixafor drug levels may be 
required. 
• Substrates of CYP3A that have a narrow therapeutic index are prohibited. 
• Sensitive CYP2D6 substrates should be avoided and other CYP2D6 substrates should be 
administered only with the approval of the Medical Monitor.  
Appendix 18.4 provides a list of commonly prescribed drugs that are inhibitors or inducers of 
CYP3A4 and substrates of CYP2D6. Known strong inducers and inhibitors are indicated. This 
list of drugs may not be a complete list, consultation with the Medical Monitor is requested for 
any concerns about concomitant medication use. 
7.4.1.4. 
Restrictions Related to P-gp inhibitors 
The following P-gp inhibitors, which are not also CYP inhibitors, are prohibited: amiodarone, 
carvedilol, dronedarone, quercetin, quinidine, ranolazine, and verapamil. Appendix 18.4 provides 
a list of commonly prescribed drugs that are P-gp inhibitors. 
7.4.2. 
Prohibited Medications, Treatments, and Procedures 
The exclusion criteria specify treatments prohibited at the time of study entry (Section 5.2).  
Patients who discontinue treatment prematurely and have completed the EOT visit, may receive 
available or investigational treatment for their disease at any time based on the judgment of their 
Confidential
Page 1295

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 72 of 115 
physician. If such treatment is initiated prior to the EOS visit (scheduled for 30 days after last 
dose of study drug), this will be recorded in concomitant medications and considered in 
assessment of any new AEs. 
7.4.3. 
Prophylactic Medications, Treatments, and Procedures 
None. 
7.4.4. 
Rescue Medications, Treatments, and Procedures 
7.4.4.1. 
Treatment of Expected Adverse Events 
Based on prior clinical experience (as detailed in Section 2.2.3), the following treatments are 
recommended for symptomatic relief of “red eye”, “dry eye”, nasal congestion (in some 
instances with nosebleed), diarrhea and facial pains, which may occur within 48 hours of 
initiation of treatment:  
• Lubricant eye drops containing carboxymethylcellulose sodium (0.5%), such as 
Refresh™ Tears or Thera Tears 
• Non-medicated saline nasal spray, such as Simply Saline™ Nasal Mist (Arm & Hammer) 
or Xlear Sinus Care Saline Nasal Spray  
• Diarrhea should be managed according to institutional standard of care  
• Acetaminophen (paracetamol) Therapy for Febrile Episodes Consistent with Acute, 
Severe, Bacterial Infections 
7.4.4.2. 
Rescue Medications for the Treatment of Acute Infections 
Patients with WHIM syndrome typically have severe neutropenia (ANC <500 cells/µL); 
however, in contrast to patients who have similar counts associated with impaired production, 
patients with WHIM syndrome rarely have acute, fatal bacterial infections. This is consistent 
with the observation that during acute infection, circulating WBC counts can increase, 
presumably reflecting cell mobilization and bone marrow release by other mechanisms. 
Administration of G-CSF will raise ANC toward the normal range, but has little, if any, effect on 
ALC [McDermott 2014] and patients on G-CSF may continue to experience infections despite 
well-conducted prophylaxis. 
Nevertheless, in some patients with WHIM syndrome presenting with febrile illness consistent 
with acute, severe bacterial infection, experienced clinicians may consider it prudent to 
administer G-CSF in addition to antibiotics and hospitalization. Provision is therefore made for 
patients meeting those criteria to be administered a course of G-CSF as rescue therapy until the 
acute process is resolved, stabilized, or determined not to reflect bacterial infection. Provision is 
also made for the use of Ig therapy if, in the opinion of the Investigator, the patient would benefit 
from this therapy. Application of these provision should be reported promptly to the Medical 
Confidential
Page 1296

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 73 of 115 
Monitor. However, if an Investigator decides that a patient requires ongoing, regularly scheduled 
treatment with G-CSF, then the patient must be discontinued from the study.   
Chronic use of Ig therapy is permitted if deemed necessary by the treating physician and after 
agreement from the Sponsor. 
7.4.4.3. 
Therapy for Warts 
Topical and systemic treatments for warts should be discontinued prior to Day 1 of treatment. If 
warts do not show an improvement from Baseline after receiving study drug for 12 weeks, 
patients will, in consultation with the Medical Monitor, have treatment with imiquimod applied 
to a subset of lesions.  
In the Extension Phase, the use of imiquimod is permitted for the treatment of warts. Laser 
treatment, surgery and bleomycin injections are not permitted. Other treatments for warts should 
be discussed with the medical monitor. 
7.4.5. 
Participant Access to Study Drug after Study Completion 
Provision is made for patients that wish to continue participation in the study to receive open-
label treatment with mavorixafor.  Section 7.3.1 describes a treatment Extension Phase of the 
study.  If regionally applicable, patients who complete study treatment will continue to receive 
study drug until it becomes available via an alternative mechanism (e.g., drug is commercially 
available, an expanded access program, etc.)  
7.5. 
Appropriateness of Measurements 
See Section 4.2. 
Confidential
Page 1297

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 74 of 115 
8. 
ADVERSE EVENTS 
8.1. 
Definitions 
8.1.1. 
Adverse Events (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product, and which does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including abnormal laboratory findings), symptom, or disease temporally associated with the 
use of an investigational product, whether or not related to the investigational product. 
An AE in a clinical study may be any of the following:  
• An unfavorable and unintended symptom reported by the patient. Patients will be 
encouraged to report treatment-emergent AEs spontaneously; general, non-directed 
questioning may also be used to elicit reports of AEs. 
• Clinical sign detected by the Investigator. Observations by other study personnel will be 
reported to the Investigator for evaluation. 
• Abnormal result from a laboratory study or other diagnostic procedure that meets at least 
one of the following criteria:  
- Results in termination of study drug; 
- Leads to treatment;  
- Leads to further diagnostic tests (other than a single repeat for confirmation);  
- Is assessed as “clinically significant” by the Investigator. 
8.1.2. 
Serious Adverse Events 
An AE or suspected adverse reaction is considered serious if, in the view of either the 
Investigator or Sponsor, it: 
• Results in death. 
• Is life-threatening. Life-threatening means that the patient was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
Confidential
Page 1298

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 75 of 115 
• Requires in-patient hospitalization or prolongation of existing hospitalization. 
Hospitalization admissions and/or surgical operations scheduled to occur during the study 
period, but planned prior to study entry are not considered AEs if the illness or disease 
existed before the patient was enrolled in the study, provided that it did not deteriorate in 
an unexpected manner during the study (e.g., surgery performed earlier than planned). 
Additional exclusions to SAE reporting include hospitalizations for: 
- Elective procedures. 
- Social/administrative reasons in the absence of an AE. 
- Expected deterioration caused by progression of the disease under study. 
• Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly/birth defect. 
• Is an important medical event. An important medical event is an event that may not result 
in death, be life-threatening, or require hospitalization but may be considered an SAE 
when, based upon appropriate medical judgment, it may jeopardize the patient and may 
require medical or surgical intervention to prevent one of the outcomes listed in the 
definitions for SAEs. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in in-patient hospitalization, or the development of drug 
dependency or drug abuse.  
8.1.3. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse drug reactions. The phrase "responses to a medicinal products" means that a 
causal relationship between a medicinal product and an AE is at least a reasonable possibility, 
i.e., the relationship cannot be ruled out. 
8.1.4. 
Suspected, Unexpected Serious Adverse Reaction 
A suspected, unexpected serious adverse reaction (SUSAR) is defined as an SAE that meets both 
the following criteria with respect to study drug:  
• Suspected — is assessed as related or possibly related to study drug (see Section 8.2.3);  
• Unexpected — compared to the study drug-related AEs described in Investigator’s 
Brochure, the event meets any of the following criteria: 
- The event was not previously described;  
- The event is now characterized as more severe (see Section 8.2.1);  
Confidential
Page 1299

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 76 of 115 
-
The event is now characterized more specifically (e.g., an event of “interstitial
nephritis” in a patient receiving an agent previously described as associated with
“acute renal failure”).
In clinical studies involving ill patients, events considered related to the natural history of the 
disease under study or to lack of efficacy (that is, the event is considered more likely related to 
those factors than to other factors, including study drug) are not considered "unexpected".  
8.1.5. 
Clinical Laboratory Adverse Events 
The Investigator will review the results of all Safety Laboratory tests (see Section 7.2.1.1) and 
designate any results outside of the reference range as either of the following:  
•
Abnormal, not clinically significant.
•
Abnormal, clinically significant.
In making this judgment, the Investigator will consider all available information, including the 
patient’s clinical condition, all available laboratory results, and the potential for false positive 
test results. In addition, laboratory studies that result in the actions specified in Section 8.1.1 will 
be classified as “abnormal, clinically significant”.  
Any result assessed as “abnormal, clinically significant” will be recorded as an AE unless it is 
consistent with one or more of the following:  
•
Process noted in the medical history:
•
Ongoing AE already recorded;
•
Expected course of the primary disease under study.
8.2. 
Classification of Adverse Events 
8.2.1. 
Severity 
The intensity (synonym: severity) of clinical AEs (i.e., symptoms reported by the patient and/or 
signs observed by the Investigator) will be assessed by the Investigator using the NCI CTCAE 
(v4.03) 5-level grading system, available on-line (see 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf). 
If the AE is not included in the NCI CTCAE, then the Investigator is to determine the intensity 
of the AE according to the following criteria: 
•
Mild (Grade 1):  AE that disappears or is easily tolerated on continuation of study drug.
•
Moderate (Grade 2):  AE sufficiently discomforting to cause interference with usual
work activities.
•
Severe (Grade 3):  AE that is incapacitating, with inability to work or perform daily
activities.
Confidential
Page 1300

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 77 of 115 
• Life-Threatening (Grade 4):  AE that is potentially life threatening.  
• Death (Grade 5):  Death related to AE.  
8.2.2. 
Grading of Laboratory Safety Tests for Reporting and Analysis 
Treatment-emergent abnormal laboratory results will be reported as AEs when assessed as 
“clinically significant” using the procedures and criteria detailed in Section 8.1.5.  
For purposes of analyzing laboratory data, all laboratory results will be graded using NCI 
CTCAE v4.03 and then summarized as “shift tables” comparing baseline and treatment-emergent 
results. This process will assure that the final study report contains complete and consistent 
analyses of safety laboratory tests.  
8.2.3. 
Relationship to Study Drug 
This determination is based on the Investigator’s clinical judgment regarding the likelihood that 
the study drug caused the AE and may include consideration of some or all of the following 
factors:  
• Alternative possible causes of the AE, including the patient’s underlying disease or 
co-morbid conditions, other drugs, other host and environmental factors; 
• Temporal sequence between the exposure to study drug and the AE;  
• Whether the clinical or laboratory manifestations of the AE are consistent with known 
actions or toxicity of the study drug;  
• Whether the AE resolved or improved with decreasing the dose or stopping the study 
drug (i.e., dechallenge); or recurred or worsened with re-exposure to the drug 
(i.e., rechallenge).  
The relationship between the study drug and the AE will be described using one of the following 
categories:  
• Related: event can be fully explained by administration of the investigational product. 
• Probably related: event is most likely to be explained by the administration of the 
investigational product rather than the subjects clinical state or other agents and/or 
therapies. 
• Possibly related: event may be explained by the administration of the investigational 
product or the subject's clinical state or other agents and/or therapies. 
• Unlikely related: event can be fully explained by the subject's clinical state or other 
agents and or therapies rather than the investigational product. 
• Unrelated (or not related): event can be fully explained by the subject's clinical state or 
other agents and or therapies. 
Confidential
Page 1301

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 78 of 115 
Related and possibly related AEs may result during the use of the study drug as planned (per 
protocol), or from abuse, withdrawal or over-dosage of the agent.  
Investigators will be asked to assess the relationship of an event to mavorixafor, based on their 
judgment and experience. 
8.2.4. 
Expectedness 
AEs meeting the criteria in Section 8.1.4 are to be considered unexpected. 
8.2.5. 
Date and Time of Onset 
The date and time at which the event was first apparent. Table 15 summarizes the basis for 
reporting the date and time of onset for the different types of AEs.  
Table 15: 
Reporting the Date and Time of Onset of AE for Different Types of Events  
Type of Event 
Examples 
Source of Date and Time of Onset 
Symptom 
Headache, feverish, paresthesia  
When first experienced by the patient 
Sign (Finding) 
Elevated BP, enlarged liver on 
physical exam 
When first observed by the Investigator or 
other study staff 
Laboratory / diagnostic result 
Neutropenia, hyperglycemia,  
lesions on brain scan 
When laboratory sample was obtained or 
diagnostic study performed 
Abbreviations: AE=adverse event; BP=blood pressure. 
The time of onset of symptoms may be appreciably earlier than the date and time the Investigator 
becomes aware of the event. Some events may be apparent to the patient and Investigator 
independently, and information from each may contribute to the final report. For example, a 
patient may report the onset of a rash two days before being seen by a physician who makes a 
diagnosis of herpes zoster based on appearance and laboratory confirmation. In that case, there is 
a single AE, with the date of onset based on the date of the initial observation by the patient and 
a specific description (herpes zoster) based on the clinical examination and tests.  
8.2.6. 
Actions Taken for Management of AE 
AEs will be followed and managed by the Investigator, including obtaining any supplemental 
studies needed to define the nature and/or cause of the event (e.g., laboratory tests, diagnostic 
procedures, consultation with other health care professionals).  
For each AE, the Investigator will categorize as follows the actions taken to manage the AE:  
• Concomitant medication — one or more medications (prescription or over-the-counter) 
were started or increased in dose; non-medication actions may also have been ordered.  
• Other action — only non-medication action(s) were ordered as management of the AE 
(e.g., bed placed in Trendelenburg position, warm compresses applied to intravenous 
access site).  
• No action — no actions were ordered for management of the AE.  
Confidential
Page 1302

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 79 of 115 
8.2.7. 
Follow-up and Outcome of AEs 
If possible, AEs will be followed until resolved (synonyms: recovered, recuperated, ended) either 
with or without sequelae, including for patients who prematurely discontinue study participation. 
For AEs that are assessed as not drug-related and are not resolved at the EOS visit, follow-up 
may be limited with the approval of the Medical Monitor.  
The outcome of each event will be described using the following categories:  
• Resolved without sequelae — the event resolved and patient returned to baseline;  
• Resolved with sequelae — the event resolved but the patient is left with residual 
problems (e.g., functional deficits, pain);  
• Resolving — at the last observation, the event was improving;  
• Not Resolved — at the last observation, the event was unchanged;  
• Death (Fatal) — to be used for the one AE which, in the judgment of the Investigator, 
was the primary cause of death;  
• Unknown — there were no observations after the onset (initial observation or report) of 
the event.  
Note: Resolving and Not Resolved may also be used for AEs that were unresolved at the time a 
patient died, but were not assessed as the primary cause of death. 
8.2.8. 
Date and Time of Outcome  
For each class of outcome as defined above, Table 16 indicates the date and time to be recorded. 
As discussed in detail for date / time of onset (see Section 8.2.5), determining the date / time an 
event resolved (ended) should reflect the type of event and the source of the information.  
Table 16: 
Date and Time of Outcome for AE by Outcome Class  
Outcome assigned to AE 
Date and Time to be Recorded 
Resolved (with or without sequelae) 
Date and time event observed or reported as resolved 
Death 
Date and time of death 
Resolving or Not Resolved 
Date and time of last observation 
Unknown 
None (see definition above) 
 
8.3. 
Time Period and Frequency for Event Assessment and Follow-Up 
Procedures for the collection and recording of AEs are as follows:  
• From obtaining informed consent through EOS, there will be active surveillance to 
identify all AEs. Events will be recorded in the AE portion of the eCRF, with particular 
attention to whether the onset of the event was before or after the administration of the 
first dose of study drug. 
Confidential
Page 1303

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 80 of 115 
• After the EOS, surveillance will be passive (only events brought to the Investigator’s 
attention will be considered) and only events assessed as SUSARs (see Section 8.1.4) 
will be recorded.  
8.4. 
Reporting Procedures 
8.4.1. 
Adverse Event Reporting 
Each patient must be carefully monitored for the development of any AEs. This information 
should be obtained in the form of non-leading questions (e.g., “How are you feeling?”) and from 
signs and symptoms detected during each examination, observations of study personnel, and 
spontaneous reports from patients.  
All AEs (serious and non-serious) spontaneously reported by the patient and/or in response to an 
open question from study personnel or revealed by observation, physical examination, or other 
diagnostic procedures occurring within the time frame specified in Section 8.3 will be 
documented in the patient’s source documents and recorded in the eCRF. Any clinically relevant 
(as determined by the Investigator) deterioration in laboratory assessments or other clinical 
findings is considered an AE and must be recorded in the patient’s source documents and in the 
eCRF.  
The AE term should be reported in standard medical terminology when possible. Also, when 
possible, signs and symptoms indicating a common underlying pathology should be noted as one 
comprehensive event. For each AE, the investigator will evaluate and report the onset, 
resolution, intensity, causality, action taken, serious criteria (if applicable), and whether or not it 
caused the patient to discontinue the study. 
8.4.2. 
Serious Adverse Event Reporting  
SAE reporting, including supporting materials, will be performed by the site using a system 
approved by the Sponsor; detailed training will be provided during site initiation. Contact 
information for guidance and assistance with SAE reporting will be provided in the Study 
Manual.  
8.4.2.1. 
Procedures for Reporting SAEs to the Sponsor  
The initial notification of each SAE will be reported within 24 hours of the time the Investigator 
(or the Investigator's designee) becomes aware that the event has occurred and will include the 
following items of information (any items not available should be explicitly noted):  
• Protocol number, study site, patient number;  
• Investigator’s name, address, and contact information (phone, fax, email);  
• Description of the event (i.e., date and time of onset, initial assessment, treatments and 
course);  
• Current status of the patient and the event;  
Confidential
Page 1304

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 81 of 115 
• Criteria by which the event was assessed as serious;  
• Date of the first administration of study drug;  
• Date of the last administration of study drug prior the event;  
• Assessment of relationship of study drug to the event;  
• Whether the study drug was discontinued or adjusted as a result of the event.  
Thereafter, signed supplemental (follow-up) information will be provided as it becomes 
available to the Investigator (either directly or as a result of investigation into a query). Such 
information includes but is not limited to:  
• Copies of relevant medical reports — including diagnostic procedures (e.g., laboratory 
tests), surgical procedures, and consultations 
• More definitive outcome for events previously reported as ongoing or unknown outcome 
8.4.2.2. 
Requirements for Expedited and Periodic Reporting of Adverse Events  
SUSARs are required to be reported rapidly to regulatory authorities and to IRBs/IECs (typically 
within 7 days for fatal or life-threatening SUSARs; within 15 days for all other SUSARs). The 
Sponsor and the Investigator will work together to meet these reporting requirements.  
8.4.2.3. 
Notification of SAEs to the Investigator by the Sponsor  
In accordance with regulatory requirements, the Sponsor will notify the Investigator of the 
occurrence of SUSARs reported by other Investigators in this or in other studies involving the 
study drug. The Investigator will promptly inform his/her IRB/IEC of such communications 
from the Sponsor and will document that notification in the Investigator’s Regulatory Binder.  
8.4.3. 
Events of Special Interest  
None. 
8.4.4. 
Reporting of Pregnancy  
Pregnancies occurring in the patient or patient’s partner while the patient is receiving study drug 
or within 1 month after the patient’s last dose of study drug will not be considered serious, but 
are to be reported using the same procedures as for SAEs described in Section 8.4.2.  
Study drug must be discontinued immediately in the event of a pregnancy in the patient. The 
patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for 
further evaluation and counseling. 
The Investigator will follow the patient / patient’s partner until completion of the pregnancy, and 
must notify the Medical Monitor of the outcome within 5 days. The Investigator will provide this 
information as a follow-up to the initial report. 
Confidential
Page 1305

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 82 of 115 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., 
spontaneous abortion [any congenital anomaly detected in an aborted fetus is to be documented], 
stillbirth, neonatal death, or congenital anomaly), then the Investigator should report it as such. 
Furthermore, all neonatal deaths that occur within 30 days of birth should be reported, without 
regard to causality, as SAEs. In addition, any infant death after 30 days that the Investigator 
suspects is related to the in-utero exposure to the study drug should also be reported. 
8.5. 
Study Halting Rules 
Stopping Rules may be developed if unexpected SAEs with causal relationship to study drug, 
including delivery procedure, appear during the study.  
The study also may be stopped based on a decision on the part of the Sponsor to suspend or 
discontinue development of study drug. 
8.6. 
Safety Oversight 
8.6.1. 
Procedures for Monitoring Risks  
Table 17: 
Monitoring Procedures for Risks Identified in Prior Studies of Mavorixafor 
Potential Risk 
Clinical Monitoring and Risk Management Procedures 
Patient monitoring and management to be 
conducted throughout the trial. 
• 
The first dose of study drug will be administered by 
study personnel; the patients will be observed post-
dose.  
• 
Ongoing monitoring will be conducted for AEs.  
• 
Ongoing monitoring of all concomitant medications 
(prescription, over-the-counter, herbal, and vitamins) 
will be conducted to avoid potential drug-drug 
interactions. 
• 
Safety laboratory tests will be conducted throughout 
the study.  
• 
Regularly scheduled clinical evaluations, including 
vital signs, physical examinations, and 
ophthalmologic examinations will be conducted. 
• 
Scheduled ECGs will be performed throughout the 
study. 
• 
Criteria for discontinuing treatment in individual 
patients due to pre-specified TLTs has been 
determined. 
Confidential
Page 1306

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 83 of 115 
Potential Risk 
Clinical Monitoring and Risk Management Procedures 
Mavorixafor is primarily metabolized through 
CYP3A4 and is a possible time-dependent 
inhibitor of CYP3A4. Monitoring and 
management of con-medications should be 
conducted.  
• 
Strong inhibitors and inducers of CYP3A4 and P-gp 
inducers are prohibited.1 
• 
If a strong inhibitor/inducer of CYP3A4 cannot be 
avoided, they are to be prescribed only with the 
approval of the Medical Monitor.  
• 
Moderate inhibitors and inducers of CYP3A4 are to 
be prescribed only with the approval of the Medical 
Monitor.  
• 
Grapefruit, grapefruit juice, and Seville orange 
containing- products are prohibited. 
• 
Substrates of CYP3A that have a narrow therapeutic 
index are prohibited. 
Mavorixafor is a moderate inhibitor of 
CYP2D6. Monitoring and management of 
con-medications should be conducted. 
• 
Avoid sensitive CYP2D6 substrates.1  
• 
Other CYP2D6 substrates should be administered 
only with the approval of the Medical Monitor. 
Mavorixafor appears to be a weak substrate of 
P-gp. 
• 
P-gp inhibitors are prohibited.1 
Emergency use of prohibited medication. 
• 
If use of a prohibited medication cannot be avoided, 
the Investigator can prescribe the prohibited 
medication and hold the study treatment.  
• 
The Investigator should report the emergency use of 
the prohibited medication to the Medical Monitor 
within 24 hours.  
AEs considered to be related and expected for 
mavorixafor can be found in the IB.2 
Guidelines for the management of AEs: 
• 
Patients who experience an AE should be carefully 
monitored for potential adverse reactions, and if 
clinically significant, symptomatic treatment should 
be instituted per institutional standard of care. 
All AEs should be reported to the Sponsor. 
• 
The sponsor will conduct a routine review of all 
reported AEs to determine safety risks and 
management.  
• 
Any risks that will potentially impact patient safety 
will be shared with the Principal Investigator. 
LFT abnormalities were observed in the animal 
model. Detailed information can be found in 
the IB.3  
• 
All clinical studies with mavorixafor have well 
defined eligibility criteria. 
• 
Safety laboratory tests including monitoring of liver 
function will occur during the study.  
Confidential
Page 1307

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 84 of 115 
Potential Risk 
Clinical Monitoring and Risk Management Procedures 
Eye anomalies were observed in one animal 
model using a different salt form than that 
being studied in this protocol. Detailed 
information can be found in the IB.4 
• 
No retinal changes were observed in beagles treated 
for 13 weeks with either the free base or the PHB salt. 
• 
No retinal changes were observed in 9-month dog 
toxicology study. 
• 
The review of 194 clinical subjects found no retinal 
disorder, except for 1 patient in Study X4P-001-
RCCA with Grade 1 age-related macular degeneration 
and Grade 1 retinal pigmentation at screening, and 1 
patient in Study X4P-001-RCCA with Grade 1 retinal 
hemorrhage and Grade 1 retinal vein occlusion, both 
of which an ophthalmologist evaluated to be related to 
the patient’s pre-existing conditions (diabetes mellitus 
and hypertension).  
• 
Central review of retinal images in 23 subjects 
including 3 patients exposed to mavorixafor more 
than 2 years showed no findings. 
• 
Patients on this study will have ongoing 
ophthalmology evaluations with retinal photographs. 
Embryo-fetal toxicity was observed in the 
animal model of an approved CXCR4 
antagonist, Mozobil (plerixafor).  
• 
WOCBP who are heterosexually active with 
childbearing potential must agree to use an effective 
method of contraception, as detailed in Section 7.4.1, 
during the study and for 4 weeks after the last dose of 
study medication, or abstain from sexual intercourse 
for this time.  
• 
WOCBP partners of male participants should use an 
effective method of contraception, as detailed in 
Section 7.4.1, to prevent passage of study intervention 
through the ejaculate during the study and for 4 weeks 
after the last dose of study medication. 
It has not been examined whether mavorixafor 
is excreted in human milk. 
• 
Breastfeeding patients are excluded from study 
participation 
Abbreviations: CYP=cytochrome P450; ECG=electrocardiogram; IB=Investigator Brochure; LFT=liver function test; P-gp=P-
glycoprotein; PHB=p-hydroxybenzoate salt; TLT=treatment-limiting toxicity; WOCBP=women of childbearing potential. 
1. 
A detailed listing of agents with potential for P-gp and CYP-related interaction is provided in Appendix 18.4.  
2. 
See IB v6.0 Section 6.2.7, Table 6-1 for Reference Safety Information 
3. 
The liver findings in beagles treated for 13 weeks with the PHB salt were greater than those observed with the free base 
drug. This (and all prior) clinical studies use only the free base drug.  
4. 
The retinal changes were observed only in albino rats treated for 26 weeks with the PHB salt. 
8.6.2. 
Data Review Committee 
During the initial Treatment Phase, all available data will be reviewed by a DRC approximately 
every 12 weeks. The DRC will include participating Investigator(s), an independent physician 
with relevant experience in clinical research and/or immune deficiency diseases, the Medical 
Monitor, and a representative of the Sponsor. During the Extension Phase, the DRC will review 
data approximately every 6 months. A detailed DRC charter is available. 
Confidential
Page 1308

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 85 of 115 
9. 
CLINICAL MONITORING 
9.1. 
External Review of the Study Conduct at Participating Sites 
All study-related materials at the site are subject to external review to ensure the safety of the 
patients, the integrity of the study data, and compliance with all applicable regulatory and 
oversight requirements. 
There are several different classes of review: 
• Monitoring — review by the Sponsor or authorized representatives, typically from the 
contract research organization coordinating the clinical conduct of the study. As detailed 
below, visits may be conducted before, during, and after the conduct of the study. 
• Audits — systematic, independent review by the quality assurance department of the 
Sponsor or authorized representatives, potentially from an organization not involved in 
the clinical conduct of the study;  
• Regulatory review — performed by representatives of regulatory authorities with 
responsibility for oversight of the study or approval of the investigational agent. These 
authorities may be from the country where the site is located or from another country.  
Monitoring and auditing visits on behalf of the Sponsor will be scheduled with the Investigator 
in advance and will be conducted at a reasonable time. To facilitate these visits, the Investigator 
will assure that the following are available: 
• Appropriate space, facilities and access to all source documents (including access to 
computerized records either electronically or as complete print outs).  
• Consent/assent forms, eCRFs, SAE forms, and medical records for all screened and 
enrolled patients.  
• Timely access to site personnel, including the Investigator, sub Investigator(s), and other 
study personnel on the day of the visit to resolve any questions that arise. 
Regulatory authorities may visit and review the site and/or Investigator during or after the study 
and may or may not notify the Investigator or the Sponsor in advance. The Investigator will fully 
cooperate with regulatory audits conducted at a reasonable time in a reasonable manner. The 
Investigator will notify the Sponsor immediately of any contact by or communication from 
regulatory authorities regarding the study.  
9.2. 
Study Monitoring Visits 
9.2.1. 
Site Qualification and Initiation Visits 
Before an investigational site can enter a patient into the study, a representative of X4 will visit 
the site to perform the following: 
Confidential
Page 1309

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 86 of 115 
• Inspect the facilities (e.g., clinical and administrative areas, pharmacy, laboratory).  
• Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, as well as the responsibilities of X4 and its representatives.  
• Review the site trial master file (TMF), including documentation related to the protocol, 
the Investigator, and other study site personnel; correspondence to and from the IRB/IEC 
the Sponsor, and their representatives.  
• Review the standard operating procedures and current practices relating to clinical and 
pharmacy activities, data handling, the IRB/IEC oversight and the informed consent 
process. 
9.2.2. 
Interim Monitoring Visits 
During the study, a clinical research associate from or representing X4 will visit 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 case report forms, and that investigational product is being 
appropriately handled and accounted. 
• Perform source data verification, including verifying the data in the eCRFs against the 
relevant source documents (see Section 11.3) and resolving any discrepancies noted.  
• Record and report any protocol deviations.  
• Confirm that AEs and SAEs have been properly documented on eCRFs; that any SAEs 
have been forwarded to X4; and that SAEs meeting criteria for reporting have been 
forwarded to the IRB/IEC.  
Between visits the clinical research associate will be available as needed to provide information 
or support to the Investigator(s) or other staff. 
9.2.3. 
Study Closeout Visit 
The study will be considered complete when all of the following have occurred:  
• All treated patients have completed all scheduled visits plus any unscheduled follow-up 
required by AEs;  
• All eCRFs have been completed, submitted and all queries resolved;  
• The study database has been locked.  
Confidential
Page 1310

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 87 of 115 
• The Sponsor or designee will then conduct a study closeout visit, which may include, but 
is not limited to, the following:  
• Review the site TMF to assure all required regulatory documents are current and 
complete.  
• Resolve any open issues from prior monitoring, audit or inspection visits.  
• Review the site’s provisions for meeting the requirements for retention study records and 
original data source.  
• Discuss possible future site audits.  
• Review the Sponsor’s publication policy.  
• Confirm compliance with requirements for notifying the IRB/IEC of study events, 
including closure.  
• Collect any unused study materials for either return to the Sponsor or disposal in a 
manner approved by the Sponsor.  
Confidential
Page 1311

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 88 of 115 
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Statistical and Analytical Plans 
A detailed statistical analysis plan has been developed.  
Reference to Baseline will be assumed to mean the observation immediately prior to the first 
dose of study treatment.  
10.2. 
Statistical Hypotheses 
Statistical methods for this Phase 2 study will be descriptive.  
10.3. 
Analysis Datasets 
Analysis populations will be defined as shown in Table 18. The Intent-to-Treat population is the 
primary population for the analysis of efficacy parameters. Additional sensitivity and 
confirmatory analyses may be performed using the Per Protocol population. The Safety 
population is the primary population for the analysis of safety endpoints. 
Table 18: 
Definition of Analysis Populations  
Population 
Definition 
Safety Population 
All patients who received at least one dose of mavorixafor. 
Intent-to-Treat Population 
All patients who received at least one dose of mavorixafor. 
Per Protocol Population 
All patients in the Intent-to-Treat population without any major 
protocol violations (as defined in statistical analysis plan) and 
with at least 1 efficacy evaluation.  
 
10.4. 
Description of Statistical Methods 
10.4.1. 
General Approach 
All data collected in this study will be documented using summary tables, figures, and/or patient 
data listings. For continuous variables, descriptive statistics (number (n), mean, median, standard 
deviation, minimum and maximum) will be presented. For categorical variables, frequencies and 
percentages will be presented. For time-to-event variables, percentages of patients experiencing 
that event will be presented and median time to event will be estimated using the Kaplan-Meier 
method. As appropriate, a 95% CI will be presented. Graphical displays will be presented, as 
appropriate. 
10.4.1.1. Missing Data 
Patients in the ITT population will be included in the primary endpoint analysis based on all 
available data. Patients with fewer than the required 3 AUC calculations for ANC or ALC, as 
Confidential
Page 1312

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 89 of 115 
appropriate, will have the last available AUC carried forward for calculation of the mean of 
3 AUC values post-treatment.  
When tabulating AE data, partial dates will be handled as follows:  
• If the day of the month is missing, the onset day will be set to the first day of the month 
unless it is the same month and year as study treatment. In that case, the event onset will 
be coded to Day 1 (the calendar day of administration of the first dose of study drug) in 
order to conservatively report the event as treatment-emergent.  
• If the onset day and month are both missing, the day and month will be assumed to be 
January 1, unless the event occurred in the same year as the study treatment. In that case, 
the event onset will be coded to Day 1 (the calendar day of administration of the first 
dose of study drug) in order to conservatively report the event as treatment-emergent.  
• For AE end dates, an event missing the day of the month will be set to the last day of the 
month, and an event missing both day and month will be set to missing. 
10.4.2. 
Analysis of the Primary Efficacy Endpoints 
The primary endpoint of this study is based on the ANC and ALC assessments collected during 
the in-residence stays and analyzed as AUC relative to pre-specified clinically meaningful 
thresholds of 600/µL and 1000/µL, respectively. The 24-hour AUC will be calculated using the 
trapezoidal method with area above threshold being positive, and area below threshold, negative. 
The results are referred to as threshold-adjusted AUC. Figure 3 illustrates the calculation of the 
24-hr AUC for a hypothetical set of ALC data. 
Confidential
Page 1313

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 90 of 115 
Figure 3: 
Calculation of 24-hr AUC for a Hypothetical Set of ALC Data 
 
Abbreviations: ALC= absolute lymphocyte count; AUC=area under the curve. 
Note: 24-hr AUC is the net sum of the interval areas. 
To calculate the AUC above the clinically meaningful threshold for each in-residence stay, the 
area below the clinically meaningful threshold will be subtracted from the total AUC. Figure 3 
illustrates the calculation of the AUC for ALC, where the red shaded area represents the area 
below the clinically meaningful threshold of 1000/µL, and the vertical blue lines represent the 
data collection time points. Patients with fewer than the required 3 AUC calculations for ANC or 
ALC, as appropriate, will have the last available AUC carried forward for calculation of the 
mean of 3 AUC values post-treatment.  
10.4.3. 
Analysis of Exploratory Endpoints 
The additional exploratory efficacy endpoints represent objectively defined, verifiable clinical 
outcomes. The exploratory efficacy endpoints will be analyzed both to provide additional 
evidence of treatment effect and to generate additional hypotheses. Non-inferential, descriptive 
analyses will be presented. Details of analyses of these endpoints will be provide in the statistical 
analysis plan.  
0
500
1000
1500
2000
2500
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
ALC Cells/µL 
Time (hours)
Confidential
Page 1314

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 91 of 115 
10.4.4. 
Safety Analyses 
The objective of safety and tolerability will be assessed by analysis of AEs and clinical 
laboratory parameters.  
All AEs will be coded using the Medical Dictionary for Regulatory Activities coding system and 
displayed in tables and data listings using SOC and preferred term. Analyses will be performed 
for TEAE, defined as any AE that begins or worsens after administration of the first dose of 
study treatment. Summary tables will be presented by SOC and PT indicating the number and 
percentage of patients with:  
• Any TEAE 
• Frequent TEAEs (defined as TEAE with incidence ≥10%) 
• AEs assessed as possibly or probably related to treatment 
• SAEs 
• AEs assessed as Grade ≥3 (severe or worse) 
• AEs leading to withdrawal  
• AEs leading to death 
AEs will be summarized by patient incidence rates; therefore, in any tabulation, a patient 
contributes only once to the count for a given SOC and PT, regardless of the number of episodes.  
The actual value and change from baseline to each on-study evaluation will be summarized for 
each clinical safety laboratory parameter, including hematology and clinical chemistry 
assessments. In the event of repeat values, the last non-missing value per study day/time will be 
used. Shift tables of laboratory data based on NCI CTCAE v4.03 grades from baseline to worst 
value and from baseline to last value on treatment will be presented. 
10.4.5. 
Adherence and Retention Analyses 
A descriptive summary of patient adherence to treatment will be produced, to include duration of 
time on therapy, number of doses received, or discontinuation. This summary will account for 
dose modification for mavorixafor and summarize the number of patients included throughout 
each dosing stage. 
10.4.6. 
Baseline Descriptive Statistics 
Descriptive statistics will be used to summarize demographics and baseline characteristics. In 
addition, a summary will be presented for patient disposition, including number of patients 
enrolled, number completing the initial Treatment Period, and number of patients who entered 
the Extension Phase. 
Medical history, medications used prior to treatment, and concomitant medications will be 
summarized. 
Confidential
Page 1315

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 92 of 115 
10.4.7. 
Planned Interim Analyses  
No interim analysis for the purposes of modifying the study is planned. 
10.4.8. 
Multiple Comparison/Multiplicity 
Not applicable. 
10.4.9. 
Tabulation of Individual Response Data 
The absolute values and change in ALC and ANC for each patient will be presented over time, 
using graphical methods that indicate all pre- and post-treatment values. In addition, cross-
tabulation summary tables that present the number and proportion of patients with increases or 
decreases in ALC and ANC over time will be produced, for appropriate categories of change 
such as increments of 0.5x103/µL. 
10.5. 
Sample Size 
Given the rarity of the disease under study as well as the known PK and PD profile of 
mavorixafor, albeit in populations other than WHIM syndrome, a traditional 3+3 dose escalation 
design was not selected. Alternatively, a small number of adult subjects (N= up to 15) will be 
treated with mavorixafor on an open-label basis. In the initial Treatment Period, safety data will 
be reviewed on an approximately every 12-week basis by the DRC. Based on subject’ ANC and 
ALC results, the mavorixafor dose may be escalated to identify a dose for use in Phase 3. A 
sample size of up to 15 patients is considered adequate for the study objectives of assessing 
safety, tolerability, and preliminary efficacy for planning Phase 3. 
Confidential
Page 1316

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 93 of 115 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Source documents are the originals of any documents used by the Investigator, hospital, or 
institution that verify the existence of the patient and substantiate the integrity of the data 
collected during the study.  
11.1. 
Medical Records 
Medical records related to the patient’s routine clinical care, including prior to or during the 
study:  
• Information obtained from the patient’s personal physicians or other third parties 
regarding the patient’s medical history or prior physical condition. 
• Medication prescription and administration records.  
• Laboratory reports, including clinical pathology and diagnostic histologic pathology.  
• Reports of imaging studies. 
• Data and reports from automated instruments (e.g., vital signs).  
• Medical records relating to scheduled and unscheduled clinical visits 
11.2. 
Study-Specific Source Documents 
Study-specific source documents include, but are not limited to, the following: 
• The informed consent form, signed and dated by the patient. 
• The site screening log.  
• Any clinical reports noted above that are scheduled as part of the protocol and have been 
annotated to indicate the significance of any abnormal findings. 
• Concomitant medication prescription and administration records.  
• Records relating to scheduled and unscheduled study visits, including, but not limited to, 
results of examinations, observations relating to AEs, and concomitant medications.  
11.3. 
Source Documents Requirements 
The following document characteristics are essential to assuring data quality and are required of 
all documents generated by the Investigator and the study team during the course of the study.  
• Be prepared at the time of the events or activities described (i.e., contemporaneously);  
• Indicate both the date and time recorded;  
Confidential
Page 1317

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 94 of 115 
• Identify the source of all recorded information (e.g., the patient, direct observations of the 
recorder, laboratory reports, external / historical sources).  
• Text should be readable and unambiguous, including application of best medical record 
practices (e.g., minimal use of abbreviations; proper numerical, dose and posology 
formats).  
Electronic health record systems must be compliant with current regulatory requirements for 
systems containing “protected health information”, including, but not limited to: 
• Security requirements for restricted access and electronic signatures 
• Electronic timestamp  
• Audit trails for any changes or amendment 
Paper documents must meet the following requirements: 
• Be written legibly in dark (preferably black) ink, including signature and date.  
• Be signed (or initialed), with date and time, by the recorder. The site must maintain a 
formal log showing for all study personnel printed name, full signatures, and initials.  
• In the event that any entry needs to be changed, a single line will be made through the 
original entry, the correct information entered (or referenced) on the same page, and the 
action initialed, dated, and (if appropriate) explained. The original entry must not be 
obscured or obliterated by multiple cross-out, correction fluid or overlay of other 
material.  
Study-specific source document forms created by the site must be reviewed by the Sponsor prior 
to use. 
11.4. 
Electronic Case Report Forms 
The Sponsor will provide a regulatory-compliant EDC system for reporting study data to a 
central facility holding the study database. All study personnel will be trained on the system and 
each will have a unique login password and electronic signature.  
The Investigator (or qualified sub-Investigator approved by the Sponsor) will review all eCRFs 
and indicate their concurrence by (electronic) signature.  
Confidential
Page 1318

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 95 of 115 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL 
12.1. 
Study Monitoring 
Monitoring and auditing procedures developed by the Sponsor or designee will be followed, in 
order to comply with ICH GCP guidelines, as described in Section 9.2.  
12.2. 
Case Report Form Completion 
The Sponsor or designee will provide the study centers with eCRFs for each patient. 
eCRFs will be completed for each study patient. It is the Investigator’s responsibility to ensure 
the accuracy, completeness, and timeliness of the data reported in the patient’s eCRF. Source 
documentation supporting the eCRF data should indicate the patient’s participation in the study 
and should document the dates and details of study procedures, AEs, and patient status.  
The Investigator, or designated representative, should complete the eCRF as soon as possible 
after information is collected, preferably on the same day that a patient is seen for an 
examination, treatment, or any other study procedure. Any outstanding entries must be 
completed immediately after the final examination. An explanation should be given for all 
missing data. 
The Investigator must electronically sign and date the Investigator’s Statement at the end of the 
eCRF to endorse the recorded data.  
12.3. 
Computerized Systems / Medical Records as Source Data 
All study data recorded on source documents are to be transcribed into the eCRFs. Any 
electronic study data are to be entered into a secure, validated data processing system and a 
backup maintained. Any changes to electronic study data will be documented. 
12.4. 
Audits and Inspections 
Authorized representatives of Sponsor or designee, a regulatory authority, or IRB/IEC may visit 
the study center to perform audits or inspections, including source data verification. The purpose 
of a Sponsor 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, ICH GCP, and any 
applicable regulatory requirements. 
The investigator should contact the Sponsor immediately if contacted by a regulatory agency 
about an inspection. 
12.5. 
Resolution of Deficiencies 
The Investigator agrees to take promptly any reasonable steps requested by the Sponsor to 
resolve any deficiencies identified as a result of monitoring, audits, inspections, protocol 
Confidential
Page 1319

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 96 of 115 
deviations, or review of any other study documentation. Failure to take adequate remedial action 
can result in suspension or termination of the study at the site. 
Confidential
Page 1320

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 97 of 115 
13.
ETHICS/PROTECTION OF HUMAN SUBJECTS
13.1. 
Ethical Standard
The Sponsor and any third party to whom aspects of the study management or monitoring have 
been delegated will undertake their assigned roles for this study in compliance with all applicable 
industry regulations, the ethical principles stated in the Declaration of Helsinki, and ICH GCP 
Guideline E6.  
ICH GCP Guideline E6 is available at: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Ste 
p4/E6_R1__Guideline.pdf  
13.2. 
Institutional Review Board/Independent Ethics Committee 
The IRB/IEC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of the patients. The study will only be conducted at study centers where 
IRB/IEC approval has been obtained. The protocol, Investigator’s Brochure, informed consent, 
advertisements (if applicable), written information given to the patients (including diary cards), 
safety updates, annual progress reports, and any revisions to these documents will be provided to 
the IRB/IEC by the Investigator. 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB/IEC as appropriate. Written IRB/IEC 
approval must be received by the Sponsor or designee before a site can enroll any patient into the 
study. 
The Investigator is responsible for informing the IRB/IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB/IEC must approve all advertising used 
to recruit patients for the study. The protocol (and other amended study documents) must be re-
approved by the IRB/IEC upon receipt of amendments and annually, as local regulations require. 
The Investigator is also responsible for providing the IRB/IEC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the investigational product. 
The Sponsor will provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/IEC according to local regulations and guidelines. 
13.3. 
Informed Consent Process  
13.3.1. 
Consent/Assent and Other Informational Documents Provided to Participants 
The Investigator(s) at each center will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk and benefit of the study. Patients 
must also be notified that they are free to discontinue from the study at any time. The patient 
Confidential
Page 1321

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 98 of 115 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. This process should be recorded in the patient’s source documentation.  
An adult patient’s signed and dated informed consent must be obtained before conducting any 
study procedures. A child patient’s (aged <18 years) signed and dated assent and the 
parent/guardian’s signed and dated informed consent must be obtained before conducting any 
study procedures. Documentation of the consenting process must be recorded in the patient’s 
source documents. 
For patients who consent to future research, a separate consent form will be signed for the 
collection and storage of additional blood samples. Subjects may also be asked to take part in 
optional pharmacogenetic research. Subjects who decline the pharmacogenetic research are 
eligible for the study if they meet all inclusion criteria and none of the exclusion criteria. The 
objective of the optional pharmacogenetic research is to assess how the genetic makeup of an 
individual affects his/her response to drugs, such as how CYP3A4*22 status may be associated 
with poor metabolism. 
13.3.2. 
Consent Procedures and Documentation 
The Investigator(s) must maintain the original, signed Informed Consent Form. A copy of the 
signed Informed Consent Form must be given to the patient, and this must be documented in the 
patient’s source documents. 
13.4. 
Participant and Data Confidentiality  
In order to maintain patient privacy, all eCRFs, study drug accountability records, study reports, 
and communications will identify the patient by initials (as allowed by local regulations) and the 
assigned patient number. The Investigator will grant monitor(s) and auditor(s) from the Sponsor 
or its designee and regulatory authority(ies) access to the patient’s original medical records for 
verification of data gathered on the eCRFs and to audit the data collection process. The patient’s 
confidentiality will be maintained and will not be made publicly available to the extent permitted 
by the applicable laws and regulations. 
Confidential
Page 1322

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 99 of 115 
14. 
DATA HANDLING AND RECORD KEEPING  
14.1. 
Data Collection and Management Responsibilities 
All study data recorded on source documents are to be transcribed into the eCRFs. Any 
electronic study data are to be entered into a secure, validated data processing system and a 
backup maintained. Any changes to electronic study data will be documented. 
14.2. 
Study Records Retention 
The Investigator will maintain all study records according to ICH GCP and applicable regulatory 
requirement(s). Records will be retained for at least 2 years after the last marketing application 
approval or 2 years after formal discontinuation of the clinical development of the investigational 
product or according to applicable regulatory requirement(s). If the Investigator withdraws from 
the responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility. The Sponsor must be notified immediately by telephone or e-mail and 
the notification confirmed in writing if a custodial change occurs. 
14.3. 
Protocol Deviations  
A protocol deviation is defined as an event in which the Investigator or site personnel did not 
conduct the study according to the Protocol, including compliance requirements and agreements. 
Guidelines for minor procedural variations (e.g., collection time of blood samples) will be agreed 
to and documented by the Investigator and the Sponsor prior to starting the study. Events 
conforming to those guidelines will not be considered deviations.  
For protocol deviations relating to individual patients, the event and relevant circumstances will 
be recorded on source documents and on the appropriate eCRF; reported to the Sponsor in a 
timely manner; and presented in the Clinical Study Report.  
Deviations that are not patient-specific (e.g., unauthorized use of an investigational agent outside 
the protocol, either human administration or laboratory use) will be reported to the Sponsor in 
writing and copies placed in the TMF.  
Deviations that can be anticipated should, if possible, be discussed with the Sponsor before being 
implemented. 
14.4. 
Publication and Data Sharing Policy 
X4 recognizes the importance of communicating the results of scientific studies, including 
clinical studies, and, therefore, encourages their publication in reputable scientific journals and 
presentation at seminars or conferences. X4 also has legitimate corporate and shareholder 
responsibilities, including, but not limited to, protecting confidential information about its 
proprietary products and obtaining patent protection for its intellectual property.  
Therefore, the following procedures apply to any communication (including written, oral, or 
electronic; manuscript, abstract, other publication, or presentation) of results or information 
Confidential
Page 1323

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 100 of 115 
arising from this study (including any ancillary studies involving study patients) to any third 
parties:  
• The proposed communication will be prepared in collaboration with the Sponsor.  
• The final proposed version must be submitted to X4 for review and comment at least 
30 days prior to presentation, submission for publication or other dissemination. 
• In the event X4 reasonably determines that a proposed communication contains 
confidential or patentable material, they may require either of the following:  
- The material be removed from the communication;  
- The communication be delayed for up to 60 additional days to permit filing the 
appropriate intellectual property protection. 
These procedures apply regardless of whether the study is completed as planned or is terminated 
prematurely for any reason.  
Confidential
Page 1324

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 101 of 115 
15. 
STUDY ADMINISTRATION 
Key personnel, along with relevant contact information, are provided in the Study Manual. 
Confidential
Page 1325

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 102 of 115 
16. 
CONFLICT OF INTEREST POLICY 
The conflict of interest policy is addressed in the Clinical Trial Agreement. 
Confidential
Page 1326

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 103 of 115 
17.
LITERATURE REFERENCES
ACTG (DIAIDS) Protocol A5210. Unpublished data. 
Al-Herz W, Bousfiha A, Casanova J-L, et al. Primary immunodeficiency diseases: an update on 
the classification from the International Union of Immunological Societies Expert Committee for 
Primary Immunodeficiency. Frontiers Immunol 2014;5 (article 162):1-33. 
AnorMED Study No. AOM 0050. Cross-reactivity of AMD11070 against natural variants of 
CXCR4. 7 October 2004. 
Aprikyan AG, Liles WC, Park JR, Jonas M, Chi EY, Dale DC. Myelokathexis, a congenital 
disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of 
bcl-x in neutrophil precursors. Blood. 2000;95:320-7. 
Badolato R, Dotta L, Tassone L, et al. Tetralogy of Fallot is an uncommon manifestation of 
Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome. J. Pediatr. 
2012;161(4):763-5. 
Badolato R, Donadieu J, and WHIM Research Group. "How I treat warts, 
hypogammaglobulinemia, infections, and myelokathexis syndrome." Blood, The Journal of the 
American Society of Hematology 130.23 (2017): 2491-2498. 
Beaussant-Cohen S, Fenneteau O, Plouvier E, et al. Description and outcome of a cohort of 8 
patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet 
J Rare Dis. 2012;7:71. 
Bies, JJ, Vece TJ, Winstead M, G. et al. "Successful Allogeneic HCT for W.H.I.M. 
Unexpectedly Complicated By Hypersensitivity Pneumonitis." Biol Blood Marrow Transplant 
2019;25(3, Supplement): S316. 
Bhar S, Yassine K, Martinez C, et al. Allogeneic Stem Cell Transplantation in a Pediatric Patient 
with Whim Syndrome. Blood 2015; 126(23):5528-5528. 
Cao YJ, Flexner CW, Dunaway S, et al. Effect of Low-Dose Ritonavir on the Pharmacokinetics 
of the CXCR4 Antagonist AMD070 in Healthy Volunteers. Antimicrob Agents Chemother. 
2008;52:1630-1634. 
Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0, 28 May 2009. U.S. 
Department of Health and Human Services, National Institutes of Health, National Cancer 
Institute. NIH Publication No. 03 5410. 
Dale DC, Bolyard AA, Kelley ML, et al. The CXCR4 antagonist plerixafor is a potential therapy 
for myelokathexis, WHIM syndrome. Blood 2011;118(18):4963-4966. 
Dale DC, Dick E, Kelley M, Makaryan V, Connelly J, Bolyard AA. Family studies of warts, 
hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome. Curr Opin Hematol 
2020;27(1):11-17. 
Confidential
Page 1327

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 104 of 115 
Dale D, Firkin F, Bolyard AA, et al. Results of a Phase 2 Trial of an Oral CXCR4 Antagonist 
Mavorixafor for Treatment of WHIM Syndrome. Blood 2020. 
Dominiak-Felden G, Cohet C, Atrux-Tallau S, Gilet H, Tristram A, Fiander A. Impact of human 
papillomavirus-related genital diseases on quality of life and psychosocial wellbeing: results of 
an observational, health-related quality of life study in the UK. BMC Public Health 
2013;13:1065. 
Dotta L, Notarandleo LD, Moratto D, et al. Long-term outcome of WHIM syndrome in 18 
patients: high risk of lung disease and HPV-related malignancies. J Allergy Clin Immunol 
Pract2019;7(5):1568-1577. 
Galli J, Pinelli L, Micheletti S, et al. Cerebellar involvement in warts Hypogammaglobulinemia 
immunodeficiency myelokathexis patients: neuroimaging and clinical findings. Orphanet J Rare 
Diseases 2019;14(1):61. 
Gulino AV, Moratto D, Sozzani S, et al. Altered leukocyte response to CXCL12 in patients with 
Warts Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome. Blood 
2004;104(2):444-452. 
Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 
are associated with WHIM syndrome, a combined immunodeficiency disease. Nature Genetics 
2003;34(1):70-74. 
Heusinkveld LE, Majumdar S, Gao J, et al. WHIM Syndrome: from Pathogenesis Towards 
Personalized Medicine and Cure. J Clin Immunol 2019;39:532–556. 
Heusinkveld LE, Yim E, Yang A, et al. Pathogenesis, diagnosis and therapeutic strategies in 
WHIM syndrome immunodeficiency. Expert Opin Orphan Drugs 2017;5(10):813-825. 
Johnson VA, Cramer YS, Rosenkranz SL, et al. Antiretroviral Activity of AMD11070 (An 
Orally Administered CXCR4 Entry Inhibitor): Results of NIH/NIAID AIDS Clinical Trials 
Group Protocol A5210. AIDS Res. Hum. Retroviruses. 2019;35(8):691–697. 
Kallikourdis K, Trovato AE, Anselmi F, et al. The CXCR4 mutations in WHIM syndrome 
impair the stability of the T-cell immunologic synapse. Blood 2013;122:666-673. 
Kriván G, Erdos M, Kállay K, et al. Successful umbilical cord blood stem cell transplantation in 
a child with WHIM syndrome. Eur J Haematol 2020;84(3):274-275. 
McDermott DH, Pastrana DV, Calvo KR, et al. Plerixafor for the Treatment of WHIM Syndrome. N 
Engl J Med 2019;380(16):e25. 
McDermott DH, De Ravin SS, Jun HS, et al. Severe congenital neutropenia resulting from 
G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis. Blood 
2010;116:2793-2802. 
McDermott DH, Liu Q, Ulrick J, et al. The CXCR4 antagonist plerixafor corrects panleukopenia 
in patients with WHIM syndrome. Blood. 2011;118(18):4957-62.  
Confidential
Page 1328

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 105 of 115 
McDermott DH, Liu Q, Velez D, et al. A phase 1 clinical trial of long-term, low-dose treatment 
of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood. 2014;123(15):2308-16. 
Moiseeva A, Rodina Y, Kuzmenko N, et al. Clinical features and immunological defects in a 
group of Russian patients with WHIM syndrome. 2019 European Society of Immunodeficiencies 
(ESID) meeting. 
Moyle G, DeJesus E, Marta Boffito M, et al. Proof of Activity with AMD11070, an Orally 
Bioavailable Inhibitor of CXCR4-Tropic HIV Type 1. Clin Infect Dis 2009;48:798–805 
NCI CTCAE v4.03, 14 June 2010 available at (accessed 6 April 2015): 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf 
Neupogen® (filgrastim) prescribing information. Amgen, Inc., 2015. 
Nyunt MM, Becker S, MacFarland RT, et al. Pharmacokinetic Effect of AMD070, an Oral 
CXCR4 Antagonist, on CYP3A4 and CYP2D6 Substrates Midazolam and Dextromethorphan in 
Healthy Volunteers. J Acquir Immune Defic Syndr 2008;47:559-565. 
Stone ND, Dunaway SB, Flexner C, et al. Multiple-Dose Escalation Study of the Safety, 
Pharmacokinetics, and Biologic Activity of Oral AMD070, a Selective CXCR4 Receptor 
Inhibitor, in Human Subjects. Antimicrob Agents Chemother 2007;51(7):2351–2358. 
Suzuki S, Toyabe S, Moroda T, et al. Circadian rhythm of leucocytes and lymphocyte subsets 
and its possible correlation with the function of the autonomic nervous system. Clin Exp 
Immunol 1997;110:500-508. 
Tassone L, Notarangelo LD, Bonomi V, et al. Clinical and genetic diagnosis of Warts, 
Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome in 10 patients. J 
Allergy Clin Immunol 2009;123(5):1170-3. 
Total WBC data provided by personal communication from Dr. David Dale, 8 Feb 2016. 
WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human 
Subjects, Available at (accessed 6 April 2015) 
http://www.wma.net/en/30publications/10policies/b3/ 
Zuelzer WW. "Myelokathexis"–A New Form of Chronic Granulocytopenia. Report of a case. N 
Engl J Med 1964;270:699-704. 
Confidential
Page 1329

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 106 of 115 
18. 
APPENDICES 
18.1. 
Revision History and Sponsor Signature 
The revision history is summarized in Table 19. Significant revisions made in each protocol 
version are provided in a separate Summary of Changes document. 
Table 19: 
Protocol Revision History 
Ver. No. 
Date 
Comment 
1.0 
01 June 2016 
Initial submission to FDA 
2.0 
05 July 2016 
Response to FDA review of IND submission; technical correction 
of Study Weeks in Schedules of Events and associated text 
3.0 
13 January 2017 
Multiple changes for clarification, reduction in some laboratory 
assessments, removal of several assessments from Phase 3 
Observation Period B1. 
4.0: Never activated 
20 March 2017 
Response to VHP Grounds for Non-Acceptance submitted as a 
final draft. Never activated/signed-off. 
4.1: US & Australia 
only 
16 May 2017 
Local changes for US & Australia (impacting the Phase 2 portion), 
including the Phase 2 dosing regimen and the addition of an 
extension phase. 
4.2: Europe only 
28 June 2017 
Change in the primary endpoint, allowed use of 
immunoglobulin therapy and additional risk/benefit language. 
4.3: US only 
01 August 2017 
Local changes for US allowing for additional dose escalation and 
“dense sampling” visits for Phase 2 patients and allowed use of 
immunoglobulin therapy. 
4.4: Australia only 
(Never activated) 
20 October 2017 
Local changes for Australia to align the country specific protocol 
with protocol version 4.3 and allowing for additional dose 
escalation and “dense sampling” visits for Phase 2 patients and 
allowed use of immunoglobulin therapy. 
4.5: US & Australia 
only 
15 December 2017 Change to the dosing regimen, including a maximum daily dose of 
400 mg QD 
4.6: US & Australia 
only 
02 April 2019 
Removed Phase 3 component; add assessments to the Extension 
visits (ophthalmologic; ANC, ALC, and PK sampling; assessment 
of warts; Ig and antibodies; revaccination; biomarkers); added 
overall study schema, Schedule of Events for the Extension Phase, 
and table for estimated blood volumes in the Extension Phase; 
updated statistical methods to align with the SAP and eliminate 
redundancy; administrative changes; minor editorial changes 
(abbreviations, punctuation, grammar); administrative changes 
5.0: US & Australia 
only 
21 December 2020 Added TAT measurements for ANC, ALC, and AMC as an 
exploratory endpoint, updated interview language, reduced patient 
burden by decreasing Extension Phase office visit frequency, 
addition of home health visit language, additional consent proposed 
Confidential
Page 1330

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 107 of 115 
for collection of genetic samples for future PGX analysis, and 
removal of 25 mg capsule details.  
Abbreviations: ALC=absolute lymphocyte count; AMC=absolute monocyte count; ANC=absolute neutrophil count; 
FDA=Food and Drug Administration; IND=Investigational New Drug Application; PGX=pharmacogenomics; 
PK=pharmacokinetics; QD=once daily; SAP=statistical analysis plan; TAT=time above threshold; US=United 
States; VHP=voluntary harmonization procedure. 
This protocol Version 5.0 has been prepared and approved by the Sponsor.  
 
 
 
X4 Pharmaceuticals, Inc. 
 
 
 
Signature 
Date 
 
07-Jan-2021
Confidential
Page 1331

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 108 of 115 
18.2. 
Quality of Life Assessment (SF-36)  
 
 
Your Health and Well-Being 
 
 
This survey asks for your views about your health.  This information will 
help keep track of how you feel and how well you are able to do your usual 
activities. Thank you for completing this survey! 
 
For each of the following questions, please mark an 
 in the one box that best 
describes your answer. 
1. 
In general, would you say your health is: 
Excellent 
Very good 
Good 
Fair 
Poor 
 
 
 
 
 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
2. 
Compared to one year ago, how would you rate your health in general 
now? 
Much better 
now than one 
year ago 
Somewhat 
better  
now than one 
year ago 
About the 
same as  
one year ago 
Somewhat 
worse  
now than one 
year ago 
Much worse 
now than one 
year ago 
 
 
 
 
 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 
 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust.  
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1332

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 109 of 115 
3. 
The following questions are about activities you might do during a 
typical day.  Does your health now limit you in these activities?  If so, 
how much? 
 
 
 
 
 
Yes,  
limited  
a lot 
Yes, 
limited  
a little 
No, not 
limited  
at all 
 
   
a Vigorous activities, such as running, lifting  
heavy objects, participating in strenuous sports ...................... 
 1 ............. 
 2 ............. 
 3 
b Moderate activities, such as moving a table, pushing  
a vacuum cleaner, bowling, or playing golf............................. 
 1 ............. 
 2 ............. 
 3 
c Lifting or carrying groceries .................................................... 
 1 ............. 
 2 ............. 
 3 
d Climbing several flights of stairs ............................................. 
 1 ............. 
 2 ............. 
 3 
e Climbing one flight of stairs .................................................... 
 1 ............. 
 2 ............. 
 3 
f Bending, kneeling, or stooping ................................................ 
 1 ............. 
 2 ............. 
 3 
g Walking more than a mile ........................................................ 
 1 ............. 
 2 ............. 
 3 
h Walking several hundred yards ............................................... 
 1 ............. 
 2 ............. 
 3 
i Walking one hundred yards ..................................................... 
 1 ............. 
 2 ............. 
 3 
j Bathing or dressing yourself .................................................... 
 1 ............. 
 2 ............. 
 3 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1333

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 110 of 115 
4. 
During the past 4 weeks, how much of the time have you had any of the 
following problems with your work or other regular daily activities as a 
result of your physical health? 
All of  
the time 
Most of  
the time 
Some of  
the time 
A little of 
the time 
None of  
the time 
     
a Cut down on the amount of  
time you spent on work or  
other activities .................................. 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
b Accomplished less than you  
would like ........................................ 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
c Were limited in the kind of  
work or other activities .................... 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
d Had difficulty performing the  
work or other activities (for  
example, it took extra effort) ........... 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
5. 
During the past 4 weeks, how much of the time have you had any of the 
following problems with your work or other regular daily activities as a 
result of any emotional problems (such as feeling depressed or anxious)? 
All of  
the time 
Most of  
the time 
Some of  
the time 
A little of 
the time 
None of  
the time 
     
a Cut down on the amount of  
time you spent on work or  
other activities .................................. 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
b Accomplished less than you  
would like ........................................ 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
c Did work or other activities  
less carefully than usual ................... 
 1 ..............
 2 .............. 
 3 .............. 
 4 ............. 
 5 
 
 
 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1334

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 111 of 115 
6. 
During the past 4 weeks, to what extent has your physical health or 
emotional problems interfered with your normal social activities with 
family, friends, neighbors, or groups? 
Not at all 
Slightly 
Moderately 
Quite a bit 
Extremely 
 
 
 
 
 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 
 
7. 
How much bodily pain have you had during the past 4 weeks? 
None 
Very mild 
Mild 
Moderate 
Severe 
Very severe 
      
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
  
 6 
 
 
8. 
During the past 4 weeks, how much did pain interfere with your normal 
work (including both work outside the home and housework)? 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
 
 
 
 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 
 
 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1335

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 112 of 115 
9. 
These questions are about how you feel and how things have been with 
you during the past 4 weeks.  For each question, please give the one 
answer that comes closest to the way you have been feeling.  How much 
of the time during the past 4 weeks… 
 
10. 
During the past 4 weeks, how much of the time has your physical health 
or emotional problems interfered with your social activities (like visiting 
with friends, relatives, etc.)? 
All of  
the time 
Most of  
the time 
Some of  
the time 
A little of  
the time 
None of  
the time 
 
 
 
 
 
  
 1 
  
 2 
  
 3 
  
 4 
  
 5 
 
All of  
the time 
Most of  
the time 
Some of  
the time 
A little of the 
time 
None of  
the time 
     
a Did you feel full of life? ..................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
b Have you been very nervous? ..........
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
c Have you felt so down in the  
dumps that nothing could  
cheer you up? ...................................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
d Have you felt calm and   
peaceful? ..........................................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
e Did you have a lot of energy? ..........
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
f Have you felt downhearted  
and depressed? .................................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
g Did you feel worn out? ....................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
h Have you been happy? .....................
 1 .............. 
 2 ..............
 3 ..............
 4 ..............
 5 
i Did you feel tired? ...........................
 1 ..............
 2 ..............
 3 ..............
 4 ..............
 5 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1336

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 113 of 115 
11. 
How TRUE or FALSE is each of the following statements for you? 
Definitely 
true 
Mostly  
true 
Don’t  
know 
Mostly  
false 
Definitely 
false 




a I seem to get sick a little 
easier than other people .................. 
 1 ..............
 2 ............. 
 3............... 
 4 .............. 
 5 
b I am as healthy as  
anybody I know .............................. 
 1 ..............
 2 ............. 
 3............... 
 4 .............. 
 5 
c I expect my health to  
get worse ......................................... 
 1 ..............
 2 ............. 
 3............... 
 4 .............. 
 5 
d My health is excellent ..................... 
 1 ..............
 2 ............. 
 3............... 
 4 .............. 
 5 
 
 
 
Thank you for completing these questions! 
 
 
SF-36v2® Health Survey  1992, 1996, 2000 Medical Outcomes Trust and QualityMetric Incorporated.  All rights reserved. 
SF-36® is a registered trademark of Medical Outcomes Trust. 
(SF-36v2® Health Survey Standard, United States (English)) 
Confidential
Page 1337

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 114 of 115 
18.3. 
LIFE QUALITY INDEX 
Baseline LQI was not collected in this Phase 2 study, therefore LQI will not be followed. 
Confidential
Page 1338

X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
Confidential 
Page 115 of 115 
18.4. 
Potential P-gp and CYP-Related Drug-Drug Interactions 
Strong CYP3A 
inhibitor1 
Strong 
CYP3A 
inducer1 
Moderate 
CYP3A 
inhibitor2 
Moderate 
CYP3A 
inducer2 
CYP3A Substrates 
with Narrow 
Therapeutic Index 
CYP2D6 sensitive 
substrate1 
CYP2D6 
moderate 
sensitive 
substrate2 
P-gp inhibitors1 
boceprevir, 
clarithromycin, 
cobicistat, conivaptan, 
danoprevir and 
ritonavir, diltiazem, 
elvitegravir and 
ritonavir, grapefruit 
juice, idelalisib, 
indinavir, itraconazole, 
ketoconazole, lopinavir 
and ritonavir, 
mibefradil, nefazodone, 
nelfinavir, paritaprevir 
and ritonavir, 
ombitasvir and/or 
dasabuvir, 
posaconazole, 
saquinavir, telaprevir, 
telithromycin, 
tipranavir and ritonavir, 
troleandomycin, 
voriconazole  
carbamazepine, 
enzalutamide, 
mitotane, 
phenytoin, 
rifampin 
(rifampicin), 
St. John’s wort 
amprenavir, 
aprepitant, 
atazanavir, 
cimetidine, 
ciprofloxacin, 
clotrimazole, 
crizotinib, 
cyclosporine 
(ciclosporin), 
darunavir and 
ritonavir, 
dronedarone, 
erythromycin, 
fluconazole, 
fluvoxamine, 
fosamprenavir, 
imatinib, 
tofisopam, 
verapamil 
bosentan, 
efavirenz, 
etravirine, 
modafinil, 
nafcillin 
alfentanil, 
cyclosporine, 
dihydroergotamine, 
ergotamine, 
everolimus, 
fentanyl, pimozide, 
quinidine, 
sirolimus, 
tacrolimus 
atomoxetine, 
desipramine, 
dextromethorphan, 
eliglustat, nebivolol, 
nortriptyline, 
perphenazine, 
pimozide, 
thioridazine, 
tolterodine, 
venlafaxine  
amitriptyline, 
encainide, 
imipramine, 
metoprolol, 
propafenone, 
propranolol, 
tramadol, 
trimipramine 
amiodarone, 
azithromycin, 
captopril, carvedilol, 
clarithromycin, 
conivaptan, 
cyclosporine, 
diltiazem, dronedarone, 
erythromycin, 
felodipine, 
itraconazole, 
ketoconazole, lopinavir 
and ritonavir, 
quercetin, quinidine, 
ranolazine, ticagrelor, 
verapamil. 
1 Prohibited. 
2 Use with Medical Monitor approval only. 
Note: This list of drugs may not be a complete list, consultation with the medical monitor is requested for any concerns about concomitant medication use. 
Sources:  
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm 
http://labeling.pfizer.com/ShowLabeling.aspx?id=759 
http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/landing/epar_search.jsp&mid=WC0b01ac058001d124 
Confidential
Page 1339