Clinical trial NCT03005327
Conditions: WHIM Syndrome
Sponsor: X4 Pharmaceuticals
Start date: 2016-12-01; Completion date: 2022-06-16
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This 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 dose selection of mavorixafor in participants with WHIM syndrome. Participants may continue treatment in an Extension Phase, if regionally applicable, until mavorixafor becomes available via an alternative mechanism (for example, drug is commercially available, an expanded access program, etc.) or until the study is terminated by the Sponsor for any reason.

Detailed description:

Arms: arm 1: Initial Treatment Phase: Participants will initiate treatment with mavorixafor at 50 milligrams (mg) once daily (QD) orally or a higher dose, with potential escalation based on area under the curve for absolute neutrophil count and absolute leukocyte count (AUCANC/ALC) values to a maximum total daily dose of 400 mg. Participants are expected to receive treatment for 24 weeks in the initial Treatment Period or until development of a treatment-limiting toxicity (TLT).

Extension Phase: All participants will receive mavorixafor; the dose will not exceed 400 mg. In the Extension Phase, treatment may continue until mavorixafor becomes available via an alternative mechanism (for example, drug is commercially available, an expanded access program, etc.) or until the study is terminated by the sponsor.
Interventions: intervention 1: X4P-001
Intervention descriptions: intervention 1: Mavorixafor will be provided as either 25 mg or 100 mg capsules.

Protocol documents:
Prot_000.pdf: 
X4 Pharmaceuticals, Inc. 
Protocol X4P-001-MKKA, Version 5.0 (21 December 2020) 
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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) 
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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 
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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 
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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 
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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 
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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 
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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 
 
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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 
 
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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 
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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 
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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 
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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.
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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 
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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. 
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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). 
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- 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. 
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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. 
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• 
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. 
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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. 
 
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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 
 
 
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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. 
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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. 
 
 
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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 
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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. 
 
 
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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. 
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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. 
 
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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 
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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 
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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. 
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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%) 
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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].  
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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.  
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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.  
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• 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:  
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• 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). 
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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 
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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 
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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, 
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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.  
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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 
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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: 
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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 
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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. 
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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. 
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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 
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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 
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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. 
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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 
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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.  
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• 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). 
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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.  
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- 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). 
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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. 
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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. 
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- 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. 
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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). 
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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 
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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: 
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- 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. 
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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 
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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. 
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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 
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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 
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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. 
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- 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. 
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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. 
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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). 
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• 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:  
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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).  
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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. 
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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 
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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 
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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. 
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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. 
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• 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);  
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-
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.
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• 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. 
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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.  
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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. 
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• 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;  
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• 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. 
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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. 
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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.  
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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. 
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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: 
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• 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.  
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• 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.  
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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 
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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. 
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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)
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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. 
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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. 
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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;  
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• 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.  
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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 
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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. 
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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 
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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. 
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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 
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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.  
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15. 
STUDY ADMINISTRATION 
Key personnel, along with relevant contact information, are provided in the Study Manual. 
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16. 
CONFLICT OF INTEREST POLICY 
The conflict of interest policy is addressed in the Clinical Trial Agreement. 
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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. 
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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.  
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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. 
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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 
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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
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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)) 
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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)) 
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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)) 
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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)) 
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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)) 
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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)) 
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18.3. 
LIFE QUALITY INDEX 
Baseline LQI was not collected in this Phase 2 study, therefore LQI will not be followed. 
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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 
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SAP_001.pdf: 
X4 Pharmaceuticals, Inc. 
Statistical Analysis Plan (SAP) X4P-001-MKKA 
Confidential 
Page 1 of 172 
Statistical Analysis Plan 
Study Title: 
A Phase 2, Open-Label, Multi-Center Trial of Mavorixafor 
in Patients with WHIM Syndrome 
Phase: 
2 
Protocol Number: 
X4P-001-MKKA 
Sponsor: 
X4 Pharmaceuticals, Inc. 
61 North Beacon Street, 4th Floor 
Boston, MA 02134 
Protocol Number: 
X4P-001-MKKA (21 December 2020, Version 5.0) 
Document Version: 
Version 3.0, 16th February 2022 
Approvals 
X4 Pharmaceuticals, Inc. 
Signatu
X4 Pharmaceuticals, Inc. 
Signatur
Premier Research 
Signatur
NCT #: NCT03005327


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Document History 
Version
Date
Author
Description
1.0
01Jun 2016
 
Initial Draft: Submitted to FDA (Initial IND 
129092, 10 June 2016
2.0 
21 Feb 2018 
 
Updated based on protocol amendments, 
increase total daily dose to 400mg, specify 
exploratory analyses and other various 
administrative updates 
3.0 
18 Sep 2020 
 
•
Updated based on protocol
amendment 4.6 (added objectives for
the extension phase, added an
updated schedule of events),
Infection rate calculation has been
added in section 6.1.2
•
Added Figure 1 and Box plot
analysis in section 6.1.4
•
Time above threshold analysis added
as section 6.1.5
•
Re-enrollment due to COVID-19
added as section 6.1.6
•
Local lab analysis and Cerba
Research lab corrections added in
section 9.2
•
Added derivations for infection rate
& infection score for 6 month time
intervals in section 6.1.2
3.0 
22 Feb 2021 
 
•
Add ITT population
•
Add handling of partial dates for
infection events
•
Updated based on protocol
amendment 5.0


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3.0 
29 July 2021 
 
• Updated infection rate calculations 
and corresponding TLFs 
• Added in 6 month time interval for 
infection rate 
3.0 
16 February 
2022 
 
• Updated TLF shells 
• Updated section 2.2.3 to note that 
local lab was used to analyze whole 
blood samples due to COVID-19 
• Added in DRC meeting timelines for 
extension phase to sections 3 and 4.3. 
• Updated laboratory baseline 
derivation 
• Updated medical history text to 
reference 12 months prior to study 
start instead of 6 months 
• Updated protocol deviations 
classification to be important/non-
important instead of major/minor 
• Updated per protocol population 
definition to reference important 
protocol violations instead of major 
protocol violations. 
 
 
 
 
 


X4 Pharmaceuticals, Inc.  
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Page 4 of 172 
Table of Contents 
Statistical Analysis Plan .................................................................................................................. 1 
Approvals ........................................................................................................................................ 1 
Document History ........................................................................................................................... 2 
List of Tables ................................................................................................................................ 10 
List of Figures ............................................................................................................................... 10 
Abbreviations ................................................................................................................................ 10 
1. 
Overview ........................................................................................................................... 12 
2. 
Study Objectives and Endpoints ....................................................................................... 12 
2.1. 
Study Objectives ......................................................................................................... 12 
2.1.1. Primary Objectives...................................................................................................... 12 
2.2. 
Study Endpoints .......................................................................................................... 12 
2.2.1. Primary Endpoints ...................................................................................................... 12 
2.2.2. Exploratory Endpoints ................................................................................................ 13 
2.2.3. Pharmacokinetic and Pharmacodynamic (PK/PD) Endpoints .................................... 14 
2.2.4. Biomarker Endpoints .................................................................................................. 15 
3. 
Overall Study Design and Plan ......................................................................................... 15 
3.1. 
Sample Size and Power ............................................................................................... 16 
3.2. 
Study Population ......................................................................................................... 16 
3.3. 
Treatments Administered ............................................................................................ 16 
3.4. 
Method of Assigning Patients to Treatment Groups................................................... 16 
3.5. 
Blinding and Unblinding............................................................................................. 16 
3.6. 
Schedule of Events ...................................................................................................... 17 
4. 
Statistical Analysis and Reporting .................................................................................... 23 
4.1. 
Introduction Of Statistical and Reproting Section ...................................................... 23 
4.2. 
Statistical Hypothesis .................................................................................................. 23 
4.3. 
Interim Analysis and Data Monitoring ....................................................................... 23 
5. 
Analysis Populations ......................................................................................................... 24 
6. 
General Issues for Statistical Analysis .............................................................................. 24 
6.1. 
General Statistical Methodology................................................................................. 24 
6.1.1. Handling of Missing Data ........................................................................................... 24 
6.1.2. Derived Variables ....................................................................................................... 25 
6.1.3. Data Conventions ........................................................................................................ 26 
6.1.4. Calculation of the AUCANC and/or AUCALC ............................................................... 26 
6.1.5. Time above threshold analysis .................................................................................... 27 
6.1.6. Re-enrollment due to COVID-19................................................................................ 28 
7. 
Study Patients and Demographics .................................................................................... 28 
7.1. 
Disposition of Patients and Withdrawals .................................................................... 28 


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7.2. 
Protocol Violations and Deviations ............................................................................ 29 
7.3. 
Demographics and Other Baseline Characteristics ..................................................... 29 
7.4. 
Medical History .......................................................................................................... 29 
8. 
Efficacy Analysis .............................................................................................................. 29 
8.1. 
Primary Efficacy Analysis .......................................................................................... 29 
8.2. 
Exploratory Efficacy Analysis .................................................................................... 29 
8.3. 
Subgroup Analysis ...................................................................................................... 30 
9. 
Safety and Tolerability Analysis ....................................................................................... 30 
9.1. 
Adverse Events ........................................................................................................... 30 
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 31 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 31 
9.1.3. Treatment Limiting Toxicities .................................................................................... 31 
9.2. 
Clinical Laboratory Evaluations ................................................................................. 32 
9.3. 
Vital Signs ................................................................................................................... 34 
9.4. 
Electrocardiograms ..................................................................................................... 34 
9.5. 
Concomitant Medication ............................................................................................. 34 
9.6. 
Exposure and Compliance .......................................................................................... 34 
10. 
Changes from Planned Analysis ....................................................................................... 35 
11. 
Other Planned Analysis..................................................................................................... 35 
11.1. Pharmacokinetic and Pharmacodynamic (PK/PD) Analysis ...................................... 35 
11.2. Biomarker Analysis .................................................................................................... 35 
12. 
References ......................................................................................................................... 36 
13. 
Tables, Listings, and Figures ............................................................................................ 37 
13.1. Planned Table Descriptions ........................................................................................ 37 
13.2. Demographic Data ...................................................................................................... 37 
13.3. Efficacy Data .............................................................................................................. 37 
13.4. Safety Data .................................................................................................................. 38 
13.5. Pharmacokinetic Data ................................................................................................. 39 
13.6. Planned Listing Descriptions ...................................................................................... 39 
13.7. Planned Figure Descriptions ....................................................................................... 40 
14. 
Tables, Listings, and Figure Shells ................................................................................... 42 
14.1. Standard Layout for all Tables, Listings, and Figures ................................................ 42 
14.2. Planned Table Shells ................................................................................................... 42 
Table 14.1.1 Subject Disposition Informed Consent Signed .................................................. 43 
Table 14.1.2 Summary of Protocol Deviations  Safety Population ........................................ 44 
Table 14.1.3 Demographics and Baseline Characteristics Safety Population ........................ 46 
Table 14.1.4 Summary of Study Drug Exposure Safety Population ...................................... 48 
Table 14.1.5 Summary of Medical History Safety Population ............................................... 49 


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Table 14.2.1.1 Summary of AUCs and Mean of AUCs for ANC by Dose Level - 
AUCANC ≥ 600/µL Threshold Safety Population ........................................................ 50 
Table 14.2.1.1.1 Summary of AUCs and Mean of AUCs for ANC by Dose Level - 
AUCANC ≥ 500/µL Threshold Safety Population ........................................................ 52 
Table 14.2.1.2 Summary of AUCs and Mean of AUCs for ALC by Dose Level  Safety 
Population ................................................................................................................... 53 
Table 14.2.2.3 Summary of Highest Grade Infections Safety Population .............................. 57 
Table 14.2.2.4 Summary of Infection Scores Safety Population ............................................ 58 
Table 14.2.3.1 Summary of Non-Genital Warts Safety Population ....................................... 59 
Table 14.2.3.2 Summary of Non-Genital Warts by location Safety Population..................... 61 
Table 14.2.4.1 Summary of Genital Warts Safety Population ................................................ 63 
Table 14.2.5 Summary of Antibody Levels following Revaccination Safety Population ...... 64 
Table 14.2.6 Summary of Rescue Medications Safety Population ......................................... 66 
Table 14.2.7 Summary of Hospitalizations Safety Population ............................................... 67 
Table 14.2.8 Summary of Ig and Specified Antibodies Safety Population ............................ 68 
Table 14.2.9 Time above Threshold (Hours) for ANC by Dose Level  Safety 
Population ................................................................................................................... 70 
Table 14.2.9.1 Time above Threshold (Hours) for ANC by Dose Level – Sensitivity 
Analysis Safety Population ......................................................................................... 70 
Table 14.2.10 Time above Threshold (Hours) for ALC by Dose Level  Safety 
Population ................................................................................................................... 70 
Table 14.2.10.1 Time above Threshold (Hours) for ALC by Dose Level – Sensitivity 
Analysis Safety Population ......................................................................................... 71 
Table 14.2.11 Time above Threshold (Hours) for AMC by Dose Level  Safety 
Population ................................................................................................................... 71 
Table 14.3.1.1 Overall Summary of Treatment-Emergent Adverse Events Safety 
Population ................................................................................................................... 72 
Table 14.3.1.2 Summary of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term Safety Population .............................................................. 74 
Table 14.3.1.3 Summary of Treatment-Emergent Adverse Events Related to Study 
Treatment by System Organ Class and Preferred Term Safety Population ................ 76 
Table 14.3.2.1 Summary of Serious Adverse Events by System Organ Class and 
Preferred Term Safety Population .............................................................................. 78 
Table 14.3.2.2 Summary of Serious Adverse Events Related to Study Treatment by 
System Organ Class and Preferred Term Safety Population ...................................... 80 
Table 14.3.2.3 Summary of Treatment-Limiting Toxicities by System Organ Class and 
Preferred Term Safety Population .............................................................................. 82 
Table 14.3.2.4 Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
System Organ Class and Preferred Term Safety Population ...................................... 83 
Table 14.3.2.5 Rate of Treatment Emergent Adverse Events by System Organ Class 
and Preferred Term Safety Population ........................................................................ 84 


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Table 14.3.2.6.1 Summary of Yearly Infection Rate for Subjects on 300mg and 400mg 
Dose Levels by 6 Month Intervals  Safety Population ............................................... 85 
Table 14.3.2.6.2 Summary of Yearly Infection Score for Subjects on 300mg and 
400mg Dose Levels by 6 Month Intervals  Safety Population ................................... 86 
Table 14.3.2.7.1 Summary of Yearly Infection Rate by Dose Level – Method 1 Safety 
Population ................................................................................................................... 87 
Table 14.3.2.7.2 Summary of Yearly Infection Rate by Dose Level – Method 2 Safety 
Population ................................................................................................................... 88 
Table 14.3.3.1 Listing of Serious Adverse Events Safety Population .................................... 89 
Table 14.3.3.2 Listing of Treatment Emergent Adverse Events Leading to 
Discontinuation Safety Population ............................................................................. 90 
Table 14.3.4.1 Listing of Out of Reference Range Laboratory Values Safety Population ..... 91 
Table 14.3.5.1.1 Summary of Actual and Change from Baseline in Hematology Results  
Safety Population ........................................................................................................ 92 
Table 14.3.5.1.2 Shift from Baseline in Hematology Results Safety Population ................... 94 
Table 14.3.5.2.1 Summary of Actual and Change from Baseline in Serum Chemistry 
Results Safety Population ........................................................................................... 95 
Table 14.3.5.2.2 Shift from Baseline in Serum Chemistry Results Safety Population........... 95 
Table 14.3.5.3.1 Summary of Actual and Change from Baseline in Coagulation Results 
Safety Population ........................................................................................................ 95 
Table 14.3.5.3.2 Shift from Baseline in Coagulation Results Safety Population ................... 95 
Table 14.3.5.4.1 Summary of Actual and Change from Baseline in Cytometry Results 
Safety Population ........................................................................................................ 95 
Table 14.3.6.1.1 Summary of Actual and Change from Baseline in Vital Signs Safety 
Population ................................................................................................................... 95 
Table 14.3.6.2.1 Summary of Actual and Change from Baseline of 12-Lead 
Electrocardiogram (ECG) Parameters Safety Population ........................................... 96 
Table 14.3.6.3.1 Summary of Ophthalmologic Examination Results (Local Reader) 
Safety Populaion ......................................................................................................... 98 
Table 14.3.6.3.2 Summary of Ophthalmologic Examination Results (Central Retinal 
Findings) Safety Populaion ......................................................................................... 99 
Table 14.3.6.4 Summary of Concomitant Medications  Safety Population.......................... 100 
Table 14.3.6.5.1 Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and 
Imiquamod – Concomitant Medications Safety Population ..................................... 101 
Table 14.3.6.5.2 Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and 
Imiquamod – Prior Medications Safety Population .................................................. 101 
Table 14.3.6.6 Summary of Actual and Change from Baseline in SF-36 QOL Scores 
Safety Population ...................................................................................................... 102 
Table 14.3.6.6 Summary of Actual and Change from Baseline in HPV Impact Profile 
(HIP) Questionnaire - Domain Scores Safety Population......................................... 102 


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Table 14.4.1 Summary of Plasma X4P-001 Concentrations by Dose Level  Safety 
Population ................................................................................................................. 103 
Table 14.4.2 Summary of Plasma X4P-001 Pharmacokinetic Parameters by Dose Level  
Safety Population ...................................................................................................... 104 
14.3. Planned Figure Shells ............................................................................................... 105 
Figure 14.4.1.1 WBC over Time by Patient Safety Population ............................................ 105 
Figure 14.4.1.2a ANC over Time by Patient Safety Population ........................................... 105 
Figure 14.4.1.2b ANC over Time by Dose Level Safety Population ................................... 105 
Figure 14.4.1.3a ALC over Time by Patient Safety Population ........................................... 106 
Figure 14.4.1.3b ALC over Time by Dose Level Safety Population .................................... 106 
Figure 14.4.1.4a Monocytes over Time by Patient Safety Population ................................. 106 
Figure 14.4.1.4b Monocytes over Time by Dose Level Safety Population .......................... 108 
Figure 14.4.1.5 Mean (+/– SE) Plasma Concentration - Time Profile of X4P-001 by 
Dose Level Safety Population ................................................................................... 109 
Figure 14.4.1.6 Mean Dose Response of ANC - Time Profile Safety Population ............... 110 
Figure 14.4.1.7 Mean Dose Response of ALC - Time Profile Safety Population ................ 111 
Figure 14.4.1.8 Mean Dose Response of Monocytes - Time Profile Safety Population ...... 111 
Figure 14.4.1.9 Box plots of WBC change from baseline ratio at 300mg and 400mg by 
Dose Level Safety Population ................................................................................... 112 
Figure 14.4.1.10 Box plots of AUC for ANC by Dose Level Safety Population ................. 113 
Figure 14.4.1.11 Scatter Plot of Time above Threshold values for ANC versus AUC for 
ANC Safety Population............................................................................................. 114 
Figure 14.4.1.12 Scatter Plot of Time above Threshold values for ALC versus AUC for 
ALC Safety Population ............................................................................................. 114 
Figure 14.4.1.13.1 Plot of Yearly Infection Rate by Dose Level Safety Population ............ 115 
Figure 14.4.1.13.2 Plot of Yearly Infection Score by Dose Level Safety Population .......... 116 
Figure 14.4.1.14.1 Plot of Yearly Infection Rate for Subjects on 300mg and 400 mg 
Dose Levels by 6 Month Intervals Safety Population .............................................. 117 
Figure 14.4.1.14.2 Plot of Yearly Infection Score for Subjects on 300 mg and 400 mg 
Dose Levels by 6 Month Intervals Safety Population .............................................. 118 
Figure 14.4.2.1 Scatter Plot of Plasma Drug Level and ANC Safety Population ................. 119 
Figure 14.4.2.2 Scatter Plot of Plasma Drug Level and ALC Safety Population ................. 119 
Figure 14.4.3.1 Mean Plasma Concentrations of X4P-001 vs Nominal Time (Dense 
Sampling Visits) by Dose Level - Linear Scale Safety Population .......................... 119 
Figure 14.4.3.2 Mean Plasma Concentrations of X4P-001 vs Nominal Time (Dense 
Sampling Visits) by Dose Level - Semi-Logarithmic Scale Safety Population ....... 119 
Figure 14.4.4.1 Subject Plasma Concentrations of X4P-001 vs Nominal Time (Dense 
Sampling Visits) by Dose Level - Linear Scale Safety Population .......................... 120 
Figure 14.4.4.2 Subject Plasma Concentrations of X4P-001 vs Nominal Time (Dense 
Sampling Visits) by Dose Level - Semi-Logarithmic Scale Safety Population ....... 120 


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14.4. Planned Listing Shells............................................................................................... 121 
Listing 16.2.1 Subject Disposition All Enrolled Patients ..................................................... 122 
Listing 16.2.2.1 Eligibility Criteria Not Met All Enrolled Patients ...................................... 123 
Listing 16.2.2.2 Protocol Deviations Safety Population ....................................................... 124 
Listing 16.2.3 Analysis Populations All Enrolled Patients ................................................... 125 
Listing 16.2.4.1 Demographics and Baseline Characteristics Safety Population ................. 126 
Listing 16.2.4.2 Medical History Safety Population............................................................. 127 
Listing 16.2.4.3.1 History of WHIM Syndrome - Hospitalizations Safety Population ........ 128 
Listing 16.2.4.3.2 History of WHIM Syndrome - Infections Managed as Out-Patient 
Safety Population ...................................................................................................... 129 
Listing 16.2.4.3.3 History of WHIM Syndrome - Prior Treatments for WHIM 
syndrome Safety Population ..................................................................................... 130 
Listing 16.2.4.3.4 WHIM Syndrome Genotyping Safety Population ................................... 131 
Listing 16.2.4.4.1 Study Drug Administration Safety Population ........................................ 132 
Listing 16.2.4.4.2 Study Drug Exposure Safety Population ................................................. 133 
Listing 16.2.4.5 Assessment of Warts Safety Population ..................................................... 134 
Listing 16.2.4.6 Revaccination Safety Population ................................................................ 135 
Listing 16.2.4.7 Bone Marrow Aspirate Safety Population .................................................. 136 
Listing 16.2.5.1 Pharmacokinetic Blood Collection and Concentrations Safety 
Population ................................................................................................................. 137 
Listing 16.2.5.2 Calculated Pharmacokinetic Parameters Safety Population ....................... 138 
Listing 16.2.6.1 ANC/ALC Sample Collection Safety Population ...................................... 139 
Listing 16.2.6.2.1 Threshold Adjusted AUC values for ANC Safety Population ................ 140 
Listing 16.2.6.2.2 Threshold Adjusted AUC values for ALC Safety Population ................. 141 
Listing 16.2.6.2.3 Time Above Threshold by Dose Level - Assessment of 
ANC/ALC/AMC  Safety Population ........................................................................ 142 
Listing 16.2.6.2.4 Time Above Threshold - Assessment of ANC/ALC/AMC with Time 
Crossed Safety Population ........................................................................................ 144 
Listing 16.2.7.1 Treatment Emergent Adverse Events Safety Population ........................... 145 
Listing 16.2.7.2 Adverse Events that occur during Screening and ended before 
Exposure to study Drug Safety Population ............................................................... 146 
Listing 16.2.7.3 Infections Reported as Adverse Events Safety Population ........................ 147 
Listing 16.2.7.4 Deaths All Enrolled Patients....................................................................... 149 
Listing 16.2.7.5 Treatment Limiting Toxicities  Safety Population ..................................... 150 
Listing 16.2.7.6 Infections in Subjects Treated on 300mg or 400 mg Dose by Time 
Period  Safety Population.......................................................................................... 151 
Listing 16.2.7.7 Infections by Dose Level Safety Population .............................................. 152 
Listing 16.2.7.8 Infections by Subject  Safety Population .................................................... 153 
Listing 16.2.8.1 Clinical Laboratory Data: Serum Chemistry Safety Population ................ 155 
Listing 16.2.8.2 Clinical Laboratory Data: Hematology Safety Population ......................... 156 


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Listing 16.2.8.3 Serology and Other Laboratory Test Results Safety Population ................ 156 
Listing 16.2.8.4 Serum Ig and Specific Antibody Laboratory Test Results Safety 
Population ................................................................................................................. 157 
Listing 16.2.8.5 Pregnancy Test Safety Population .............................................................. 158 
Listing 16.2.8.6 Coagulation Laboratory Test Results Safety Population ............................ 159 
Listing 16.2.8.7 Urinalysis Laboratory Test Results Safety Population ............................... 160 
Listing 16.2.8.8 CytometryTest Results Safety Population .................................................. 161 
Listing 16.2.9.1 Prior or Concomitant Medications Safety Population ................................ 162 
Listing 16.2.9.2 Vital Signs Measurements Safety Population ............................................ 163 
Listing 16.2.9.3 12-Lead Electrocardiograms Safety Population ......................................... 164 
Listing 16.2.9.4 Physical Examinations Safety Population .................................................. 165 
Listing 16.2.9.5 Ophthalmologic Examination (Site Assessment) Safety Population ......... 166 
Listing 16.2.9.6 Ophthalmologic Examination (Central Readings) Safety Population ........ 167 
Listing 16.2.9.7 Rescue Medications Safety Population ...................................................... 168 
Listing 16.2.9.8 SF-36 QOL Safety Population .................................................................... 169 
Listing 16.2.9.9.1 HPV Impact Profile (HIP) Questionnaire Safety Population .................. 171 
Listing 16.2.9.9.2 HPV Impact Profile (HIP) Questionnaire - Domain Scores Safety 
Population ................................................................................................................. 172 
 
List of Tables 
Table 1: Schedule of Events – Initial Treatment Period ............................................................... 18 
Table 2: Schedule of Events – Extension Phase ........................................................................... 21 
Table 3: Overview of Conversion Factors .................................................................................... 33 
 
List of Figures 
Figure 1: Calculation of 24-hr AUC for a Hypothetical Set of ALC Data. .................................. 27 
Abbreviations 
ABBREVIATION DEFINITION OR DESCRIPTION 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
AMC 
Absolute monocyte count 
ANC 
Absolute neutrophil count 
ATC 
Anatomical Therapeutic Chemical classification 
AUC 
Area under the plasma concentration curve 
AUCALC 
Area under the plasma concentration curve for absolute lymphocyte 
count 
AUCANC 
Area under the plasma concentration curve for absolute neutrophil count 
BLQ 
Below the limit of quantification 
BMI 
Body mass index 


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BOCF 
Baseline-observation-carried-forward 
Cmax 
Maximum concentration 
CRF 
Case report form 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events  
CXCR4 
Chemokine receptor type 4 
DRC 
Data review committee  
ECG 
Electrocardiogram 
eCRF 
Electronic Case report form 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FACS 
Fluorescence activated cell sorting 
G-CSF 
Granulocyte-colony stimulating factor 
HIP 
HPV Impact Profile 
ICH 
International Council for Harmonisation 
iCSR 
Interim Clinical Study Report 
Ig 
Immunoglobulin 
LOCF 
Last-observation-carried-forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
PBMC 
Peripheral blood mononuclear cells 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
QD 
Once Daily 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration  
WBC 
White blood cell 
WHIM 
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis 
WHO-DD 
World Health Organization Drug Dictionary 


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1.
Overview
This Statistical Analysis Plan (SAP) describes the planned analyses and data presentation for the 
Phase 2 component of the Phase 2 Study X4P-001-MKKA, titled “A Phase 2, Open-Label, 
Multi-Center Trial of Mavorixafor in Patients with WHIM Syndrome”.   
The development of this SAP is based on Protocol Version 5.0, dated 21st December 2020. The 
structure and content of this SAP provides sufficient detail to meet the requirements identified by 
the Food and Drug Administration (FDA), European Medicines Agency (EMA), and 
International Council for Harmonisation (ICH) of Technical Requirements for Registration of 
Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical Trials. All work 
planned and reported in this SAP will follow internationally accepted guidelines, published by 
the American Statistical Association and the Royal Statistical Society, for statistical practice.   
The analyses described in this SAP will be used to support the clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Post-hoc exploratory analyses not identified in 
this SAP may be performed to further examine study data. Any post-hoc analyses will be clearly 
identified as such in the CSR. 
2.
Study Objectives and Endpoints
2.1. 
Study Objectives 
2.1.1. 
Primary Objectives 
The objectives of the initial treatment period are: 
•
To evaluate safety and tolerability of mavorixafor (X4P-001) in patients with WHIM
syndrome.
•
To assess the dose required to achieve a consistent increase in circulating neutrophils and
lymphocytes in patients with WHIM syndrome.
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, cutaneous
warts, vaccine titers, and neutrophil and lymphocyte counts.
2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoints 
The primary endpoints of the study are: 
•
To determine the safety and tolerability of X4P-001; and
•
To evaluate the mean area under the curve (AUC) of the absolute neutrophil count (ANC)
AUCANC and/or AUCALC (absolute lymphocyte count) collected over 24-hour period


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above clinically meaningful thresholds during the initial treatment phase of the study 
(first 6 month). 
2.2.1.1. 
Safety and Tolerability 
Safety and tolerability will be evaluated by the following: 
• Treatment-emergent adverse events (TEAEs) 
• Adverse events (AEs) assessed as related, possibly, or probably related to treatment by 
grade (all grades and grade ≥3) 
• Serious adverse events (SAEs)  
• Deaths 
• Discontinuations due to AEs 
o  
• Vital signs 
• Clinical laboratory test results 
o Hematology 
o Serum chemistry 
o Pregnancy test (as applicable)  
• Physical examination findings 
• 12-lead ECG results 
• Ophthalmology (local and central) 
 
2.2.1.2. 
24-Hour AUCANC and/or AUCALC 
The primary efficacy endpoint is the mean 24-hour AUCANC and/or AUCALC above the clinically 
meaningful thresholds. The clinically meaningful threshold for ANC is ≥600/μL and for ALC is 
≥1000/μL. 
2.2.2. 
Exploratory Endpoints 
• 
Time above threshold values for ANC, AMC, and ALC, as applicable, will be 
calculated using the ANC and ALC assessments collected during the 24-hour collection 
times and analyzed as percentage of time (from initial to final value obtained during each 
of these visits) above the clinically meaningful thresholds of 500/μL and 1000/μL Time 
(hours)>ANC Threshold500, Time (hours)>ALC Threshold1000), respectively. These 
parameters will be compared between dose levels to determine if there is a dose-
dependent change in the respective Time (hours)>Time Above Thresholds.  
• Frequency and severity of infections (severity assessed as Grade 1 to 5 (protocol only 
mention Grade 1 to 4) using National Cancer Institute [NCI] Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.03 or higher).  
• Number of Cutaneous 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, and comparing 
number of lesions, size of largest lesion, and patient-reported morbidity at baseline to end 
of Treatment Period. 


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• 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 
12 weeks of treatment. 
• Frequency of events requiring rescue therapy (granulocyte-colony stimulating factor 
[G- CSF] and/or intravenous immunoglobulins [Ig]).   
• Rate of hospitalization events will be evaluated based on the information collected in 
the 12 months prior to start of participation in Study X4P-001-MKKA through end of 
Phase 2 Treatment Period and end of the study or data cutoff for the interim and final 
Clinical Study Report (CSR). 
• Circulating white blood cells (WBCs) - Absolute and fold change from baseline in 
total WBC counts, and in absolute numbers of lymphocytes, neutrophils, monocytes, and 
lymphocyte subpopulations cells.  
o Correlation of ANC and ALC levels with plasma drug levels 
• Ig and specific antibodies 
o Changes from baseline in levels of total IgG, IgG subclasses, IgA, IgD, IgE and 
IgM. 
• Bone marrow aspirates – Optional (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 SF-36 short form survey, Life Quality Index (LQI) and 
Human papillomavirus (HPV) Impact Profile (HIP). 
2.2.3. 
Pharmacokinetic and Pharmacodynamic (PK/PD) Endpoints 
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 (-15 min), 30, 60, 90 min (each ±5 min) and 2, 3, 4, 8, 12, 16, 24 hr (each ±15 
min). 
Additional time point 0 samples (trough) will be collected at Day 1 and Weeks 9, 17 and 25. 
Blood samples for plasma levels of X4P-001 will be analyzed for X4P-001 concentration using 
reversed-phase high performance liquid chromatography with tandem mass spectrometry 
detection. The PK parameters include AUC, maximum concentration (Cmax) and time to 
maximum concentration (Tmax). X4P-001 concentration and PK parameters will be analyzed by 
treated patients and dosage regimen over the preceding week. 
 
The in-residence stay will be rescheduled in the event of recent infection, administration of 
antibiotics, or of rescue therapy with G-CSF or intravenous Ig. Whole blood samples could be 
analyzed in local laboratories instead of a central laboratory due to COVID-19 restrictions, ANC 
and ALC were determined by standard methods. ANC and/or ALC will be calculated over time 
by patient and by dose. A full PK analysis plan will be developed separately from this document. 


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2.2.4. 
Biomarker Endpoints 
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 naïve T cells, memory T cells, B cells, transitional B cells, 
NK cells, and monocytes.  
3. 
Overall Study Design and Plan 
Patients will be scheduled for several 24-hour visits to permit collection of serial samples over 
24 hours for determination of ANC/ALC and plasma drug levels. This will be calculated as the 
mean AUC over the 24-week Treatment Phase and Extension Phase, as data are available. 
During the initial Treatment Phase, all available safety data will be reviewed approximately 
every 12 weeks by a Phase 2 Data Review Committee (DRC). 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. 
During the scheduled 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. Patients may 
receive standard of care antibiotics in the event of infection, but may not receive routine G-CSF 
or immunoglobulin therapy as a prophylactic treatment. 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 therapy if applicable (see Section 7.4.4.2 of the 
Protocol). 
Participation in the initial Treatment Phase of the study is considered complete after 24 weeks of 
treatment with X4P-001 or until development of a TLT. For the definition of a treatment limiting 
toxicity, please see Section 5.7 of the Protocol. Thereafter, patients may continue participation in 
an open-label Phase 2 Extension Phase of the protocol where dose escalation and/or additional 
in-residence stays may be permitted.   
Phase 2 Extension Phase 
With the agreement of the Investigator, patients may 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, patients may have their dose escalated and have additional 
in-residence or dense-sampling visits conducted during the Extension Phase.  
Patients from the Phase 2 study receiving less than the selected Phase 3 dose may choose to 
receive the recommended Phase 3 dose once determined. The patient’s participation in the 
Extension Phase will be complete when study treatment is discontinued, and all Extension Phase 
visits are complete. The procedures during the extension phase are described in Section 7.3.1 of 
the Protocol in detail. 


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3.1. 
Sample Size and Power 
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. 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. 
3.2. 
Study Population 
The target patient population is adult patients with a confirmed diagnosis of WHIM syndrome to 
be eligible for the study. 
3.3. 
Treatments Administered 
The investigational drug is X4P-001, which is administered orally once daily not to exceed 
400 mg daily dose. Patients either received a 25 mg capsule strength or a 100 mg capsule 
strength. Patients who received lower doses (50 mg to 200 mg QD) received 25 mg capsules 
until it was determined that higher doses would be necessary (i.e., total daily dose not to exceed 
400 mg). Therefore, after September 2017 patients either switched to or started initial dosing at a 
larger capsule strength (100 mg) when it was determined by the Investigator and Sponsor that 
higher daily doses (300 mg and 400 mg) would be appropriate. 
3.4. 
Method of Assigning Patients to Treatment Groups 
All patients will be treated with X4P-001 open-label. 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 of the protocol). 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. 
3.5. 
Blinding and Unblinding 
Not applicable. 


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3.6. 
Schedule of Events 
For a detailed schedule of events, please see Table 1. 


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Table 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 
 
 


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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. 
2Screening 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 patient’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 


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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. 
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 of the Protocol 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 of the Protocol for details. 
11 Women of childbearing potential only. 
12 Women of childbearing potential (see Section 7.4.1.1 of the Protocol 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 of the Protocol 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 of the Protocol. 
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 of the Protocol 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 of the Protocol). 
19 Daily diary for study drug administration, temperature, activities of daily living, antibiotic usage, and unscheduled healthcare visits for infection. 


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Table 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 of the Protocol) 
X 
X 
X 
Pregnancy test (WOCBP only) 
X 
X 
X 
Ophthalmological examination (Section 7.1.1.8 of the Protocol) 
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 of the Protocol) 
X 
PK dense sampling (optional) (Section 7.1.2 of the Protocol) 
X 
Assessments of warts 
X 
Serum Ig and specific antibodies 
X 
Revaccination (optional) (Section 7.1.1.4 of the Protocol) 
X 
Biomarker Time 0 sample (Section 7.1.3 of the Protocol) 
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 


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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 count; WOCBP=Woman of childbearing potential. 
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 of the Protocol.


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4.
Statistical Analysis and Reporting
After at least 4 patients have completed treatment during the Phase 2 treatment period, the DRC 
will review all available data and make a recommendation regarding the recommended Phase 3 
dose (RP3D). At that point, the iCSR was generated summarizing all planned analyses identified 
in the protocol and in this SAP for the Phase 2 treatment and extension portion of the study.   
A final clinical study report (CSR) summarizing all planned analyses identified in the study 
protocol and in this analysis plan will be generated after the last patient has completed his/her 
last visit and the database has been locked. Any post-hoc analysis not identified in this SAP but 
completed will be documented and reported in the CSR.  
4.1. 
Introduction Of Statistical and Reproting Section 
Descriptive statistics will be provided for all safety, exploratory and PK endpoints. The analyses 
results will be presented by dose levels. 
For continuous variables, the number of patients (n) with non-missing values, the mean, standard 
deviation, median, and ranges will be provided. The minimum and maximum will be reported 
with the same degree of precision (i.e., the same number of decimal places) as the observed data. 
Measures of location (mean and median) will be reported to 1 degree of precision more than the 
observed data and measures of spread (standard deviation [SD]) will be reported to 2 degrees of 
precision more than the observed data. 
For categorical variables, summaries will include the frequency and percentage of patients who 
are in the particular category. In general, the denominator for the percentage calculation will be 
based upon the total number of patients in the study population, unless otherwise specified. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
4.2. 
Statistical Hypothesis 
Statistical hypothesis testing will be performed in order to evaluate the Phase 2 primary and 
exploratory objectives. All statistical analyses will be descriptive. Statistical evaluation for the 
primary endpoint of increase in ALC and/or ANC will be based on demonstration of a significant 
increase in these parameters as threshold-corrected AUC relative to clinically meaningful values, 
as described in protocol Section 10.4.2. The null hypothesis test is defined as an AUC ≤0, with 
an alternative that the respective parameter (ALC or ANC) is >0.  
4.3. 
Interim Analysis and Data Monitoring 
No formal interim analyses are planned for this study; however, safety data will be reviewed by a 
Phase 2 DRC that includes all 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 initial Treatment Phase, all available safety data 
will be reviewed approximately every 12 weeks by a Phase 2 DRC. During the Extension Phase, 
the DRC will review data approximately every 6 months. Detailed information regarding the 
DRC is described in the DRC Charter.  


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After at least 4 patients have completed 12 weeks of treatment, the DRC will review all available 
safety data and make recommendations regarding the course of the study. The expected 
outcomes of the DRC review include: 
•
Continuation of the Phase 2 component with further observation.
In addition, based on the experience in Phase 2 with both safety and efficacy data, a 
recommended dose regimen for Phase 3 will be selected by the Sponsor with input from the 
DRC. A subset of analyses will be performed for meetings with the scientific community (e.g., 
American Society for Hematology).  
Once the recommended Phase 3 dose has been determined, an iCSR will be generated to 
summarize the open label, Phase 2 findings prior to proceeding to the Phase 3 portion of the 
study. 
5.
Analysis Populations
The analysis populations for this study are as follows: 
•
Intent to Treat (ITT): The ITT Population includes all patients who received at least
one dose of the study medication(mavorixafor).
•
Safety Population (SP): The Safety Population includes all patients who received at
least one dose of the study medication (mavorixafor). Safety and ITT populations are
identical.
•
Per Protocol (PP) Population: All patients in the ITT population without any important
protocol violations (as defined in the SAP) and at least one efficacy evaluation. Active
infections during efficacy evaluation and/or missing samples may be excluded.
6.
General Issues for Statistical Analysis
6.1. 
General Statistical Methodology
All data will be presented in data listings. Descriptive summaries will be provided where 
appropriate for each of the safety and exploratory endpoints. Baseline characteristics and safety 
data will be summarized using the safety population unless otherwise specified.  
Data processing, statistical analyses and graphical representations will be performed primarily 
using SAS® (version 9.4 or higher). All PK parameter estimations will be performed using 
Phoenix WinNonlin® software (Version 6.4 or higher; Pharsight, Cary, NC).  
Unless otherwise indicated, all statistical tests will be 2-sided and tested at a significance level of 
p-value=0.05. All tests performed for secondary or for exploratory endpoints (specified in 
Section 8.1) will be exploratory in nature.
6.1.1. 
Handling of Missing Data 
For the mean of AUCANC and/or AUCALC during 24-hour sampling, last-observation-carried-
forward (LOCF) method will be used to impute missing AUC values. Each AUC will be 


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calculated based on 11 samples collected over a 24-hour period. There will be no imputation for 
intermediate missing values within any AUC calculations during 24-hour sampling. If the last 
sample (the sample for 24-hour) is missing, the baseline-observation-carried-forward (BOCF) 
method will be used to impute the missing value. For patients who are missing all AUC 
assessments, the mean AUC value will be set to missing. 
A sensitivity analysis will be performed in which there are no modifications made for missing 
data. For the Phase 2 analysis, comparisons of the results with and without imputations will be 
reviewed and analyzed in order to determine appropriate data handling methods to be used in a 
future Phase 3 trial. 
The following rules will be applied to the programming logic to handle missing or partial 
concomitant medication dates. 
 
For prior infection events with partial dates (day and/or month missing), the following rules will 
be applied to identify events occurring approximately a year before first study treatment 
administration and to include them as occurring 12 months prior to treatment initiation in 
infection reporting outputs: 
• If infection onset year is the same as year of first study treatment administration, or 
• If infection onset year is one less than year of first study treatment administration and 
initial treatment was administered in January, or 
• If infection onset year is one less than year of first study treatment administration and 
infection onset month is on or after the month of initial treatment administration. 
If the prior infection onset date is complete, then the event will be classed as taking place 12 
months prior to first study treatment administration if it falls within 365 days prior to first study 
treatment dose. 
6.1.2. 
Derived Variables 
• Day 1 is defined as the day that first study dose is administered.  
• If the assessment is prior to Day 1, then Study day = Assessment date - date of Day 1; 
otherwise Study Day = Assessment date – date of Day 1 + 1. 
• Baseline = Last non-missing observation immediately prior to the first dose of study 
medication. For the laboratory data, if an infection event occurred ± 1 day of the baseline 
observation or the baseline value is 2x higher than the inclusion criteria value then the 
screening value will be assigned as the baseline value. If a patient had a Splenectomy 
prior to screening then the values can be 2x higher than the inclusion criteria. 
• 
Change from Baseline = post baseline value – value at Baseline. 
• 
Fold-change = Value ÷ Baseline. 
• 
Infection Rate = Number of infection events ÷ duration of treatment exposure (in years). 
• 
Summary of dose level infection rate: 1. total number of infection events for all patients 
within each dose level ÷ total duration of exposure (in years) for all patient within each 
dose level; 2. For each patient calculate the infection rate for each dose level, then 
calculate the average for all patients for each dose level. 
• Infection Score = (Number of infection events × severity) ÷ exposure (in years). 


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• 
Summary of dose level infection score: For each patient calculate the infection score for 
each dose level, then calculate the average for all patients for each dose level. 
• For each 6 month time interval: 
o Infection Rate of 6 month time interval = Number of infection events occurred in 
6 month time interval ÷ 0.5. 
o Infection Score 6 month time interval = (Number of infection events occurred in 6 
month time interval × severity) ÷ 0.5. 
6.1.3. 
Data Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or figures but will be included in listings. Adverse events will be 
coded using the Medical Dictionary for Regulatory Activities (MedDRA) (Version 19.0 or higher). 
A treatment related AE is any AE with a relationship to the study drug (i.e., possibly, probably or 
related). 
• Missing severity of an AE will be imputed to the maximum severity (In case the severity 
is graded and the maximum grade corresponds to death, the grade immediately below the 
maximum grade should be used). 
• Missing relationship to study drug of an AE will be imputed to the strongest possible 
relationship.  
• Any TEAE will be summarized under the dose level of onset. 
• If the start date and the dose of onset is missing, the TEAE will be summarized in the 
lowest possible dose level the patient received. 
 
6.1.4. 
Calculation of the AUCANC and/or AUCALC 
The ANC and ALC sampling will be performed during the in-residence stays. The area under 
curve (AUC) for each parameter ANC and ALC will be calculated and analyzed relative to 
pre-specified clinically meaningful thresholds of AUCANC ≥ 600/µL and AUCALC ≥ 1000/µL, 
respectively. A separate table for AUC for ANC by dose level will be presented where the 
threshold of AUCANC ≥ 500/µL. 
 
Patients are scheduled for 24-hour measurements of ANC and ALC via blood samples collected 
as follows:  
 
• Time 0 (-15 min), 30, 60, 90 min (each ± 5 min) and 2, 3, 4, 8, 12, 16, 24 hr (each 
±15 min) 
 
Additional visits may occur at the discretion of the Sponsor and with the agreement of the 
Investigator both during the 24-week treatment period and/or the Extension Phase. 
For patients receiving study drug, time 0 represents time of oral dosing that morning (typically 
between 7 and 8 am) and the sample will be drawn pre-dose. The 24-hour AUC will be 
calculated using the trapezoidal rule with area above threshold being positive, and area below 
threshold, negative. The results are referred to as threshold-adjusted AUC.  


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Patients with AUCANC <2000 cell•hr/µL or AUCALC <5000 cell•hr/µL after an in-residence stay 
will have X4P-001 daily dose increased in 100 mg increments up to a maximum daily dose of 
400 mg QD.  
Figure 1: 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 1 
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. 
Box-plots of AUC for ANC at doses up to 400 mg doses will be generated. 
The mean ANC, ALC and absolute monocyte count (AMC) values will be plotted from 0-24 
hours at all the dose levels. 
6.1.5. 
Time above threshold analysis 
Patients are scheduled for 24-hour measurements of ANC and ALC via blood samples collected 
at the following scheduled timepoints: Time 0 (-15 min), 30, 60, 90 min (each ± 5 min) and 2, 3, 
...J 
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4, 8, 12, 16, 24 hr (each ±15 min). During these time points, the time above thereshold is the 
total time a patients ANC and ALC values were above a pre-defined threshold. The threshold is 
defined as 500/uL for ANC and as 1000/uL for ALC. For example, if a patients ANC value is 
600 at 30 mins and 700 at 60 mins, then the patients ANC values was above the threshold for 30 
mins (60 mins – 30 mins). If the ANC value was 800 at 4 hours and 400 at 8 hours then the 
patients ANC value was above the threshold from 4 hours until the time between 4 and 8 hours 
when the ANC value went below the pre-defined threshold of 500. This time is estimated using 
linear interpolation.  
The time above threshold will be calculated for AMC based on the age and gender specific 
threshold as described in the following table: 
 
Age (year) 
Gender 
Threshold (/uL) 
>=18 
F 
250 
 
M 
290 
 
A scatter plot showing the correlation of time above threshold for ANC, ALC vs AUC for ANC 
and ALC will be generated.  
The dense samples collected on 9th to 10th October 2017 (Extension visit 1, 300mg dose) for 
patient 
, the dense samples collected on 12th to 13th February 2018 (Extension visit 3, 
400mg dose) for patient 
, and the dense samples collected on 21st February 2018 (Week 
21, 400mg dose) for patient 
 occurred during an infection event. These values will be 
excluded from the summary tables of absolute WBC, ANC, ALC, AMC; and TAT and AUC of 
ANC, ALC, and AMC. Dense sample data for subject 
 will be excluded from the TAT 
summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at 
screening. 
As a sensitivity analysis, separate summary tables of TAT will be presented including the dense 
sample data for 
. 
6.1.6. 
Re-enrollment due to COVID-19 
The re-enrollment visit for the two patients (
, 
) who dropped out the study due to 
study fatigue for about 6 months (400mg dose), and were re-enrolled on the study due to the fear 
of infection during the covid pandemic, will be mapped as Extension Visit 6 (re-enroll). All data 
will be presented in the listings. Data within the drop-out period will be excluded from the 
summary tables for infection, warts and other safety data analyses. 
7. 
Study Patients and Demographics  
7.1. 
Disposition of Patients and Withdrawals 
The patient disposition table will include the number and percentage of patients who completed 
the initiation phase of the study, the number and percentage of patients entered into the extension 
phase, the number and percentage of patients who discontinue from the study along with the 
reasons for discontinuation, and number and percentage of patients analysis population The 
percentage in this table will be based on all patients enrolled in the Phase 2 study. 


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7.2. 
Protocol Violations and Deviations 
Protocol deviations will be identified and classified as non-important or important and if 
COVID-19-related, and reviewed when preparing the Phase 2 analysis prior to the final database 
lock. Protocol deviations will be summarized by catogory using the Safety population. 
7.3. 
Demographics and Other Baseline Characteristics 
Descriptive summaries of demographics and other baseline conditions will include age, gender, 
race, ethnicity, height, weight, body mass index (BMI) and will be presented by dose levels and 
capsule strength received.  
7.4. 
Medical History 
The number and percent of patients reporting medical histories, grouped by MedDRA system 
organ class (SOC) and preferred term (PT) (coded using MedDRA Version 19.0 or higher), will 
be presented by dose level and a listing will be provided. Similarly, the history of WHIM 
syndrome manifestations (i.e., date of diagnosis, mutational status, and the following history in 
the 12 months prior to study entry: hospitalizations for infection, number and type of infections 
managed as an out-patient, any prior medical treatments for WHIM disease) will be summarized 
and presented by dose level and a listing will be provided. The Safety population will be used to 
perform these analyses. 
8.
Efficacy Analysis
8.1. 
Primary Efficacy Analysis
The AUCANC and/or AUCALC will be analyzed by week using descriptive statistics and presented 
by dose level.  A patient listing of the AUC values will be provided.  
The primary efficacy analysis will be performed with the missing data handling method 
described in Section 6.1.1 and without imputations.  
8.2. 
Exploratory Efficacy Analysis 
The following exploratory analyses will be performed: 
•
Time above threshold values for ANC, AMC, and ALC, as applicable, will be
calculated using the ANC, AMC, and ALC assessments collected during the 24-hour
collection times and analyzed as percentage of time (from initial to final value obtained
during each of these visits) above the clinically meaningful thresholds of 500/μL and
1000/μL (Time (hours) >ANC Threshold500, Time (hours) >ALC Threshold1000, and age
and gender specific AMC thresholds), respectively. These parameters will be compared
between dose levels to determine if there is a dose-dependent change in the respective
Time (hours)>Thresholds.
•
Frequency and severity of infections (severity assessed as Grade 1 to 5 using NCI
CTCAE Version 4.03 or higher).


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• Number of warts – applicable only to patients with cutaneous warts at baseline and 
comparing number of warts to that at end of Treatment Period.  
• Severity of genital warts – applicable only to patients with genital warts, and comparing 
number of lesions, size of largest lesion, and patient-reported morbidity. 
• Improvement in 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 12 weeks of treatment. 
• Frequency of events requiring rescue therapy (granulocyte-colony stimulating factor 
[G-CSF] and/or intravenous immunoglobulins [Ig]).   
• Rate of hospitalization events for the X4P-001 treated patients will be evaluated based 
on the information collected in the 12 months prior to start of participation in Study X4P-
001-MKKA through end of Phase 2 Treatment Period or data cutoff for the iCSR. 
• Circulating white blood cells (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 ANC and ALC levels with plasma drug 
levels 
• Ig and specific antibodies 
o Changes from baseline in levels of total IgG, IgG subclasses, IgA, IgD, IgE and 
IgM. 
• 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 SF-36, LQI and HIP. 
 
The Safety population will be used to perform all the exploratory analyses. 
8.3. 
Subgroup Analysis 
There are no planned subgroup analyses for the Phase 2 study.  
9. 
Safety and Tolerability Analysis 
Safety variables will include TEAEs, SAEs, deaths, discontinuations due to AEs, vital signs, 
physical examinations, ophthalmology, laboratory tests, 12-Lead electrocardiograms (ECG), , 
concomitant medications and study drug exposure. The safety population will be used to perform 
these analyses. 
9.1. 
Adverse Events 
Adverse events will be coded using MedDRA Version 19.0 or higher. The severity of an AE will 
be graded according to the NCI CTCAE, Version 4.03 or higher. 
The causal relationship of an AE to the study drug is determined by the investigator as 
Unrelated, Unlikely Related, Possibly Related, Probably Related, and Definitely Related. These 
will be mapped to Unrelated (Unrelated and Unlikely Related) and Related (Possibly Related, 
Probably Related, and Definitely Related). A summary table will be presented for the following: 


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•
All TEAEs
•
TEAEs all grades and grade 3 or higher
•
TEAEs by relationship to study drug all grades and grade 3 or higher
•
TEAEs leading to discontinuation of study drug
•
SAEs regardless of causality and treatment related
•
AEs leading to death
•
AEs of special interest
•
TLTs
TEAEs are defined as any AEs that begin or worsen on or after the start of study drug through 10 
days after the last dose of study drug.  
The incidence of TEAEs will be summarized by SOC and PT. TEAEs will also be summarized 
using Investigator assessment of the relationship to study drug (related or not related) and by 
maximum severity. TEAEs leading to study drug discontinuation and those resulting in 
premature withdrawal from study will be tabulated and listed.  
If a patient experiences multiple AEs under the same PT within a SOC, then the patient will be 
counted only once for that PT within that SOC. If a patient experiences the same AE more than 
once with different intensity or grade, then the event with the highest grade will be tabulated in 
“by grade” tables. 
9.1.1. 
Adverse Events Leading to Withdrawal 
Summary tables of TEAEs leading to the discontinuation of the study drug and AEs leading to 
premature withdrawal from the study will be provided. Data listings will be provided as well.  
9.1.2. 
Deaths and Serious Adverse Events 
A summary of serious adverse events will be provided by SOC and PT and presented by dose 
level. The SAEs will also be listed. In addition, any deaths that occur during the study will be 
listed. 
9.1.3. 
Treatment Limiting Toxicities  
A TLT event for X4P-001 is defined as an AE that meets both of the following criteria: 
1. Is assessed by the Investigator as possibly or probably related, or related to X4P-001 (see
Section 8.2.3 of the study Protocol).
2. Represents one of the following events (grading as defined by the NCI CTCAE, v4.03 or
higher) (see Section 8.2.1 of the study Protocol):
•
Is a Grade 3 or Grade 4 clinical event, except 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 with the following exceptions:
o
Grade 3 electrolyte abnormalities that persist <72 hrs and do not require
hospitalization.


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o 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: 
o AST/ALT increased >3x ULN (Grade 2) with total bilirubin increased >2x ULN 
in the absence of cholestasis. 
o Retinopathy – confirmed treatment-emergent retinopathy. 
o Platelets <50,000/mm3 (Grade 3) with bleeding or <25,000/mm3 (Grade 4). 
 
A summary of TLTs will be provided by SOC and PT and presented by dose level.  
9.2. 
Clinical Laboratory Evaluations 
Laboratory safety tests will be performed by central (CRL and Cerba Research) and local lab 
facilities. Descriptive summaries of actual (absolute) values and changes from baseline values 
will be provided for hematology and chemistry by dose level and visit.  
For tests with categorical results, the number and percentage of patients in each category will be 
provided by dose level. In the event of repeat test results, the last non-missing value per study 
day/time will be used.  
 
A shift table presenting the number and percentage of patients with clinical laboratory values 
classified as below, within, or above the normal range at post baseline visit and in relation to 
baseline will be provided for each clinical laboratory analyte (i.e., hematology and chemistry). 
A listing for the laboratory test results will be provided and all values that are outside the normal 
range will be flagged. 
 
As central labs changed from CRL to Cerba Research during the study a correction factor needs 
to be applied to the test results from Cerba Research as specified in the table below to 
standardise the results and align them with the original central lab data. The correction will not 
need to be applied to the normal ranges.  
For the local lab values, no conversion will be performed. 
 
 


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Table 3: Overview of Conversion Factors 
Test 
USA patients 
AUS patients 
Testing lab 
at CRL 
Testing lab at 
Cerba Research 
Correction factor 
Testing lab 
at CRL 
Testing lab at Cerba 
Research 
Correction factor 
Rubella 
IgG 
LabCorp 
Cerba (France) Paris 
N A 
Sydpath 
Cerba (France) Paris 
N A 
Rubeola 
IgG 
CRL USA 
Cerba (France) Paris 
N A 
Sydpath 
Cerba (France) Paris 
N A 
IgG1 
LabCorp 
Cerba (France) Paris 
LabCorp (g/L) = 1.310804 
+ 0.791798 * CerbaCR FRA 
(g/L) 
Sydpath 
Cerba (France) Paris 
Sydpath (g/L) = 1.411672+ 
1.037855 * CerbaCR FRA 
(g/L) 
IgG2 
LabCorp 
Cerba (France) Paris 
LabCorp (g/L) = 0.746442 
+ 0.817308 * CerbaCR FRA 
(g/L) 
Sydpath 
Cerba (France) Paris 
N A 
IgG3 
LabCorp 
Cerba (France) Paris 
LabCorp (g/L) = 0.08375 + 
0.875 * CerbaCR FRA (g/L) 
Sydpath 
Cerba (France) Paris 
Sydpath (g/L) = 0.0304221 + 
0.466234 * CerbaCR FRA 
(g/L) 
IgG4 
LabCorp 
Cerba (France) Paris 
LabCorp (g/L) = 0.0590315 + 
0.788288 * CR FRA (g/L) 
Sydpath 
Cerba (France) Paris 
Sydpath (g/L) = 0.0226538 + 
1.230769 * CR FRA (g/L) 
IgG 
LabCorp 
NWHL 
LabCorp (mg/dL) = 17.410089 
+ 1.074362 * CR USA (mg/dL) 
Sydpath 
SDS 
Laverty 
N A 
IgA 
LabCorp 
NWHL 
LabCorp (mg/dL) = -8.2 + 
1.085714 * CR USA (mg/dL) 
Sydpath 
SDS 
Laverty 
N A 
IgE 
CRL USA 
NWHL 
CRL USA (IU/mL) =-0.858757 
+ 0.817047 * CR USA (IU/mL) 
Sydpath 
SDS 
Laverty 
Sydpath (IU/mL) = 
11.903864 + 1.005829 * CR 
AUS (IU/mL) 
IgM 
CRL USA 
NWHL 
N A 
Sydpath 
SDS 
Laverty 
N A 
 
 


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9.3. 
Vital Signs 
Descriptive summaries of actual (absolute) values and changes from baseline values will be 
provided for vital signs including weight (kg), heart rate (bpm), systolic blood pressure (mmHg), 
diastolic blood pressure (mmHg), and temperature (oC) by dose level. 
A listing of the vital sign measurements will also be provided. Results outside the normal range 
will be flagged.  
9.4. 
Electrocardiograms 
The following ECG parameters will be recorded: HR, RR, PR interval, QRS, QT, QTc interval 
(the correction method QTcF will be calculated). 
 
Descriptive summaries of actual values and changes from baseline to each visit will be presented 
for ECG measures of HR (bpm), RR interval (ms), PR interval (ms), QRS (ms), QT (ms), and 
QTc interval (ms). These summaries will be presented by treatment group as appropriate. 
 
Shift tables comparing baseline ECG investigator interpretation (normal, abnormal, not clinically 
significant or abnormal, clinically significant) to each study visit will be summarized by dose 
level.   
9.5. 
Concomitant Medication 
Prior medications as well as prior WHIM treatment, and concomitant medications will be 
summarized descriptively using counts and percentages of patients taking each medication, 
classified using World Health Organization Drug Dictionary (WHO-DD) Anatomical 
Therapeutic Chemical (ATC) classes and PT. Prior WHIM medications, prior medications and 
concomitant medications will be presented separately. The use of antibiotics, G-CSF, 
Immunoglobulins, and imiquamod will be tabulated separately.  
• A prior medication is any medication that is started or ended prior to the first dose of 
the study medication. 
• A concomitant medication is any medication taken or ongoing on or after the first 
dose of the study medication. 
• A medication is both prior and concomitant if it started prior to and is ongoing on or 
after the first dose of the study medication.  
9.6. 
Exposure and Compliance 
The study drug will be dispensed in bottles and using a web-based treatment diary, each patient 
will record the number of capsules taken. The bottles will be examined visually at each clinic 
visit for the purpose of assessing study drug compliance. Percent compliance will be calculated as 
follows: [1 – (Total number of capsules returned/Total number of capsules dispensed)] × 100. 
Patient compliance with study drug will be summarized by patient, treatment duration overall, 
dose, treatment duration by dose and capsule strength. All study drug administration data will be 
displayed in a listing. 
 


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10. 
Changes from Planned Analysis 
The following analyses were not described in the protocol but will be presented in the TLFs:  
- 
A separate table for AUC for ANC by dose level will be presented where the threshold of 
AUCANC ≥ 500/µL. 
- 
As a sensitivity analysis, separate summary tables of TAT will be presented including the 
dense sample data for 
. 
11. 
Other Planned Analysis 
11.1. Pharmacokinetic and Pharmacodynamic (PK/PD) Analysis 
Pharmacokinetic Analysis 
The PK parameters (AUC, Tmax and Cmax), will be determined for each patient following each 
specified visit, using a non-compartmental analysis based on the plasma concentration versus 
time dataset. Additional parameters may be estimated if warranted and if data permit. 
 
Plasma X4P-001 concentration and PK parameters (AUC, Cmax, Tmax) will be summarized at 
each timepoint using descriptive statistics, including number of patients, arithmetic mean, 
geometric mean, SD, median, maximum, minimum, and coefficient of variation (%CV). These 
summaries will be presented by dose level. All figures will be presented using both linear and 
semi-logarithmic scales. All plasma concentration data and PK parameters will be displayed in 
data listings. 
 
Plasma concentration of X4P-001 below the limit of quantification (BLQ) occurring before Tmax 
will be set to 0. BLQ plasma concentrations occurring after Tmax will be set to missing. If 
sufficient data are missing for a given patient, that patient may be considered non-evaluable for 
PK analysis. All plasma concentration data and PK parameters will be displayed in data listings. 
The above descriptive summary will be performed using the PK population. 
 
Pharmacodynamic Analysis 
AUC of ANC and ALC will be determined for each patient and each dose level. Individual 
ANC/ALC values vs time will be plotted. Mean ANC/ALC values vs time will be plotted by 
dose level. X4P-001 concentration vs ANC/ALC by timepoint will be presented in scatter plots 
by dose.  
   
The PK and PD data collected in this study may be combined with data from other studies in a 
population pharmacokinetic (pop PK) analysis to assess covariate effects on the PK of X4P-001 
and the PKPD correlation between exposure and ANC/ALC to support dose selection. A separate 
PK analysis plan will be developed. 
11.2. Biomarker Analysis 
Biomarker data will be summarized descriptively, including actual value and change from 
baseline. Summaries will be presented overall. All biomarker data will be displayed in data 
listings with the cell subset name such as naïve T cells, memory T cells, B cells, transitional B 
cells, NK cells, and monocytes mentioned in the protocol. The above descriptive summary will 
be performed using the safety population 


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12. 
References 
1. Study protocol X4P-001-MKKA version 5.0 dated 21 December 2020 
 
2. Study eCRF version 12.0 dated 17 February 2021 
 
3. ASA. (1999) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, August 7, 1999. http://www.amstat.org/about/ethicalguidelines.cfm 
 
4. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998. 
 
5.  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. 
 
 
 


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13. 
Tables, Listings, and Figures 
13.1. Planned Table Descriptions 
The following are planned summary tables for protocol X4P-001-MKKA. Tables will be 
numbered according to the nomenclature used to support the CSR when the Premier Research 
CSR template is used. However, the table numbering structure can be modified per the sponsor’s 
request to meet compatibility with the sponsor’s CSR template. 
13.2. Demographic Data  
Table 1: Demographic Data Summary Tables  
Table 
Number 
Population 
Table Title/Summary 
14.1 Displays of Demographics and Disposition Data 
14.1.1 
Informed Consent 
Signed 
Subject Disposition 
14.1.2 
Safety Population Summary of Protocol Deviations 
14.1.3 
Safety Population Demographics and Baseline Characteristics 
14.1.4 
Safety Population Summary of Study Drug Exposure 
14.1.5 
Safety Population Summary of Medical History 
13.3. Efficacy Data  
Table 2: Efficacy Data Summary Tables 
Table 
Number 
Population 
Table Title/Summary 
14.2 Displays of Exploratory Summaries 
14.2.1.1 
Safety Population Summary of AUCs and Mean of AUCs for ANC by Dose Level - 
AUCANC ≥ 600/µL Threshold 
14.2.1.1.1 Safety Population Summary of AUCs and Mean of AUCs for ANC by Dose Level - 
AUCANC ≥ 500/µL Threshold 
14.2.1.2 
Safety Population Summary of AUCs and Mean of AUCs for ALC by Dose Level 
14.2.2.1 
Safety Population Summary of Infection Rates 
14.2.2.2 
Safety Population Summary of Infections by Severity 
14.2.2.3 
Safety Population Summary of Highest Grade Infections 
14.2.2.4 
Safety Population Summary of Infection Scores 
14.2.3.1 
Safety Population Summary of Non-Genital Warts 
14.2.3.2 
Safety Population Summary of Non-Genital Warts by location 
14.2.4.1 
Safety Population Summary of Genital Warts  
14.2.5 
Safety Population Summary of Antibody levels Following Revaccination 
14.2.6 
Safety Population Summary of Rescue Medications 
14.2.7 
Safety Population Summary of Hospitalizations 
14.2.8 
Safety Population Summary of Ig and Specified Antibodies  
14.2.9 
Safety Population Time above Threshold for ANC by Dose Level 
14.2.9.1 
Safety Population Time above Threshold for ANC by Dose Level – Sensitivity 
Analysis 
14.2.10 
Safety Population Time above Threshold for ALC by Dose Level 
14.2.10.1 
Safety Population Time above Threshold for ALC by Dose Level – Sensitivity 
Analysis 
14.2.11 
Safety Population Time above Threshold for Monocytes by Dose Level 


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14.2.11.1 
Safety Population Time above Threshold for Monocytes by Dose Level – Sensitivity 
Analysis 
13.4. Safety Data 
Table 3: Safety Data Summary Tables 
Table 
Number 
Population 
Table Title/Summary 
14.3.1 Summary of Treatment Emergent Adverse Events 
14.3.1.1 
Safety Population Overall Summary of Treatment-Emergent Adverse Events 
14.3.1.2 
Safety Population Summary of Treatment-Emergent Adverse Events by System 
Organ Class and Preferred Term 
14.3.1.3 
Safety Population Summary of Treatment-Emergent Adverse Events Related to 
Study Treatment by System Organ Class and Preferred Term  
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events 
14.3.2.1 
Safety Population Summary of Serious Adverse Events by System Organ Class and 
Preferred Term  
14.3.2.2 
Safety Population Summary of Serious Adverse Events Related to Study Treatment 
by System Organ Class and Preferred Term  
14.3.2.3 
Safety Population Summary of treatment-limiting toxicities by System Organ Class 
and Preferred Term  
14.3.2.4 
Safety Population Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by System Organ Class and Preferred Term  
14.3.2.5 
Safety Population Rate of Treatment Emergent Adverse Events by System Organ 
Class and Preferred Term 
14.3.2.6.1 Safety Population Summary of Yearly Infection Rate for Subjects on 300mg and 
400mg Dose Levels by 6 Month Intervals 
14.3.2.6.2 Safety Population Summary of Yearly Infection Score for Subjects on 300mg and 
400mg Dose Levels by 6 Month Intervals 
14.3.2.7.1 Safety Population Summary of Yearly Infection Rate by Dose Level – Method 1 
14.3.2.7.2 Safety Population Summary of Yearly Infection Rate by Dose Level – Method 2 
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events 
14.3.3.1 
Safety Population Listing of Serious Adverse Events  
14.3.3.2 
Safety Population Listing of Treatment Emergent Adverse Events Leading to 
Discontinuation  
14.3.4 Abnormal Laboratory Value  
14.3.4.1 
Safety Population Listing of Out of Reference Range Laboratory Values  
14.3.5 Laboratory Data Summary Tables 
14.3.5.1.1 Safety Population Summary of actual and Change from Baseline in Hematology 
Results  
14.3.5.1.2 Safety Population Shift from Baseline in Hematology Results  
14.3.5.2.1 Safety Population Summary of actual and Change from Baseline in Serum 
Chemistry Results 
14.3.5.2.2 Safety Population Shift from Baseline in Serum Chemistry Results  
14.3.5.3.1 Safety Population Summary of actual and Change from Baseline in Coagulation 
Results 
14.3.5.3.2 Safety Population Shift from Baseline in Coagulation Results  
14.3.5.4.1 Safety Population Summary of actual and Change from Baseline in Cytometry 
Results 
14.3.6 Other Safety Data Summary Tables 
14.3.6.1.1 Safety Population Summary of actual and Change from Baseline in Vital Signs  
14.3.6.2.1 Safety Population Summary of actual and Change from Baseline of 12-Lead 
Electrocardiogram (ECG) Parameters 


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14.3.6.3.1 Safety Population Summary of Ophthalmologic Examination Results (Local Reader) 
14.3.6.3.2 Safety Population Summary of Ophthalmologic Examination Results (Central 
Retinal Findings) 
14.3.6.4 
Safety Population Summary of Concomitant Medications  
14.3.6.5.1 Safety Population Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and 
imiquamod – Concomitant Medications 
14.3.6.5.2 Safety Population Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and 
imiquamod – Prior Medications 
14.3.6.6 
Safety Population Summary of SF-36 QOL 
14.3.6.7 
Safety Population Summary of HPV Impact Profile (HIP) Questionnaire 
13.5. Pharmacokinetic Data 
Table 4: Pharmacokinetic Data Summary Tables 
Table Number 
Population 
Table Title/Summary 
14.4 Pharmacokinetic Data Summary Tables 
14.4.1 
Safety Population 
Summary of Plasma X4P-001 Concentrations by Dose Level 
14.4.2 
Safety Population 
Summary of Plasma X4P-001 Pharmacokinetic Parameters 
by Dose Level 
 
13.6. 
Planned Listing Descriptions 
The following are planned patient data listings for protocol X4P-001-MKKA.  Data listings will 
be numbered according to the nomenclature used to support the CSR when the Premier Research 
CSR template is used. However, the listing numbering structure can be modified per the 
sponsor’s request to meet compatibility with the sponsor’s CSR template. 
 
Table 5: Planned Listings 
Data Listing 
Number 
Population 
Data Listing Title / Summary 
16.2.1 Patient Discontinuations/Completions 
16.2.1 
All Enrolled Patients Subject Disposition 
16.2.2 Protocol Deviations 
16.2.2.1 
All Enrolled Patients Eligibility Criteria Not Met 
16.2.2.2 
Safety Population 
Protocol Deviations 
16.2.3 Analyses Populations 
16.2.3 
All Enrolled Patients Analysis Populations 
16.2.4 Demographic Data and Other Baseline Characteristics 
16.2.4.1 
Safety Population 
Demographics and Baseline Characteristics 
16.2.4.2 
Safety Population 
Medical History 
16.2.4.3.1 
Safety Population 
History of WHIM Syndrome - Hospitalizations 
16.2.4.3.2 
Safety Population 
History of WHIM Syndrome - Infections Managed as Out-
Patient 
16.2.4.3.3 
Safety Population 
History of WHIM Syndrome - Prior Treatments of WHIM 
Syndrome 
16.2.4.3.4 
Safety Population 
WHIM Syndrome Genotyping 
16.2.4.4.1 
Safety Population 
Study Drug Administration 
16.2.4.4.2 
Safety Population 
Study Drug Exposure 
16.2.4.5 
Safety Population 
Assessment of Warts 
16.2.4.6 
Safety Population 
Revaccination 
16.2.4.7 
Safety Population 
Bone Marrow Aspirate 


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16.2.5 Drug Concentration Data 
16.2.5.1 
Safety Population 
Pharmacokinetic Blood Collection and Concentrations 
16.2.5.2 
Safety Population 
Calculated Pharmacokinetic Parameters 
16.2.5.3 
Safety Population 
PK Sample Collection  
16.2.6 Individual Efficacy Response Data 
16.2.6.1 
Safety Population 
ANC/ALC Sample Collection 
16.2.6.2.1 
Safety Population 
Threshold Adjusted AUC values for ANC 
16.2.6.2.2 
Safety Population 
Threshold Adjusted AUC values for ALC 
16.2.6.2.3 
Safety Population 
Time Above Threshold by Dose Level - Assessment of 
ANC/ALC/AMC  
16.2.6.2.4 
Safety Population 
Time Above Threshold - Pharmacodynamic Assessment of 
ANC/ALC/AMC with Time Crossed 
16.2.7 Adverse Event Listings (by Patient) 
16.2.7.1 
Safety Population 
Treatment Emergent Adverse Events 
16.2.7.2 
Safety Population 
Adverse Events that occur during Screening and ended 
before Exposure to study Drug 
16.2.7.3 
Safety Population 
Infections Reported as Adverse Events 
16.2.7.4 
Safety Population 
Deaths 
16.2.7.5 
Safety Population 
Treatment Limiting Toxicities 
16.2.7.6 
Safety Population 
Infections in Subjects Treated on 300mg or 400mg Dose by 
Time Period 
16.2.7.7 
Safety Population 
Infections by Dose Level 
16.2.7.8 
Safety Population 
Infections by Subject 
16.2.8 Laboratory Values by Patient 
16.2.8.1 
Safety Population  
Clinical Laboratory Data: Serum Chemistry 
16.2.8.2 
Safety Population 
Clinical Laboratory Data: Hematology 
16.2.8.3 
Safety Population 
Serology and Other Laboratory Test Results 
16.2.8.4 
Safety Population 
Serum Ig and Specific Antibody Laboratory Test Results 
16.2.8.5 
Safety Population 
Pregnancy Test Results 
16.2.8.6 
Safety Population 
Coagulation Laboratory Test Results 
16.2.8.7 
Safety Population 
Urinalysis Laboratory Test Results 
16.2.8.8 
Safety Population 
Cytometry Test Results  
16.2.9 Other Clinical Observations and Measurements (by Patient) 
16.2.9.1 
Safety Population 
Prior or Concomitant Medications 
16.2.9.2 
Safety Population 
Vital Signs Measurements 
16.2.9.3 
Safety Population 
12-Lead Electrocardiograms  
16.2.9.4 
Safety Population 
Physical Examinations 
16.2.9.5 
Safety Population 
Ophthalmologic Examination (Site Assessment) 
16.2.9.6 
Safety Population 
Ophthalmologic Examination (Central Readings) 
16.2.9.7 
Safety Population 
Rescue Medications 
16.2.9.8 
Safety Population 
SF-36 QOL 
16.2.9.9.1 
Safety Population 
HPV Impact Profile (HIP) Questionnaire 
16.2.9.9.1 
Safety Population 
HPV Impact Profile (HIP) Questionnaire - Domain Scores 
 
13.7. 
Planned Figure Descriptions 
The following are planned summary figures for protocol X4P-001-MKKA. They will be 
numbered according to the nomenclature used to support the CSR when the Premier Research 
CSR template is used. However, the figure numbering structure can be modified per the 
sponsor’s request to meet compatibility with the sponsor’s CSR template. 
 
Table 6: Planned Figures 


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Figure Number 
Population 
Figure Title/Summary 
Figure 14.4.1.1 
Safety Population WBC Over Time by Patient 
Figure 14.4.1.2a 
Safety Population ANC Over Time by Patient 
Figure 14.4.1.2b 
Safety Population ANC Over Time by Dose Level 
Figure 14.4.1.3a 
Safety Population ALC Over Time by Patient 
Figure 14.4.1.3b 
Safety Population ALC Over Time by Dose Level 
Figure 14.4.1.4a 
Safety Population Monocytes Over Time by Patient 
Figure 14.4.1.4b 
Safety Population Monocytes Over Time by Dose Level 
Figure 14.4.1.5 
Safety Population Mean (+/– SE) Plasma Concentration - Time Profile of 
X4P-001 by Dose Level 
Figure 14.4.1.6 
Safety Population Mean Dose Response of ANC-Time Profile 
Figure 14.4.1.7 
Safety Population Mean Dose Response of ALC-Time Profile 
Figure 14.4.1.8 
Safety Population Mean Dose Response of Monocytes-Time Profile 
Figure 14.4.1.9 
Safety Population Box plots of WBC change from baseline ratio at 300mg 
and 400mg by Dose Level 
Figure 14.4.1.10 
Safety Population Box plots of AUC for ANC by Dose Level 
Figure 14.4.1.11 
Safety Population Scatter Plot of Time above Threshold values for ANC 
versus AUC for ANC 
Figure 14.4.1.12 
Safety Population Scatter Plot of Time above Threshold values for ALC 
versus AUC for ALC 
Figure 14.4.1.13.1 
Safety Population Plot of Yearly Infection Rate by Dose Level 
Figure 14.4.1.13.2 
Safety Population Plot of Yearly Infection Score by Dose Level 
Figure 14.4.1.14.1 
Safety Population Plot of Yearly Infection Rate for Subjects on 300mg and 
400mg Dose Levels by 6 Month Intervals 
Figure 14.4.1.14.2 
Safety Population Plot of Yearly Infection Score for Subjects on 300mg 
and 400mg Dose Levels by 6 Month Intervals 
Figure 14.4.2.1 
Safety Population Scatter Plot of Plasma Drug Level and ANC  
Figure 14.4.2.2 
Safety Population Scatter Plot of Plasma Drug Level and ALC  
Figure 14.4.3.1 
Safety Population Mean Plasma Concentrations of X4P-001 vs Nominal 
Time (Dense Sampling Visits) by Dose Level - Linear 
Scale 
Figure 14.4.3.2 
Safety Population Mean Plasma Concentrations of X4P-001 vs Nominal 
Time (Dense Sampling Visits) by Dose Level - 
Semi-logarithmic Scale 
Figure 14.4.4.1 
Safety Population Subject Plasma Concentrations of X4P-001 vs Nominal 
Time (Dense Sampling Visits) by Dose Level - Linear 
Scale 
Figure 14.4.4.2 
Safety Population Subject Plasma Concentrations of X4P-001 vs Nominal 
Time (Dense Sampling Visits) by Dose Level - 
Semi-logarithmic Scale 


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14. 
Tables, Listings, and Figure Shells 
14.1. 
Standard Layout for all Tables, Listings, and Figures 
The following standard layout will be applied to all Tables, Listings, and Figures in support of this study. Note that programming 
notes may be added if appropriate after each TLF shell.  
14.2. 
Planned Table Shells 
 
 


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Table 14.1.1 
Subject Disposition 
Informed Consent Signed 
Disposition
Overall
(N=XX)
Study Populations [1] 
 All Enrolled Patients 
X (XX.X%) 
 ITT Population 
X (XX.X%) 
 Safety Population 
X (XX.X%) 
 Per Protocol Population 
X (XX.X%) 
Completion Status [2] 
 Completed Initial Treatment Period 
X (XX.X%) 
 Prematurely Discontinued from Study 
X (XX.X%) 
 <<Ongoing>> 
X (XX.X%) 
 In the Extension Phase 
X (XX.X%) 
Reasons for discontinuation 
 Lost to Follow-up 
X (XX.X%) 
 Protocol Violation 
X (XX.X%) 
 Adverse Event 
X (XX.X%) 
 Death 
X (XX.X%) 
 Patient Withdrew Consent 
X (XX.X%) 
 Principal Investigator Decision 
X (XX.X%) 
 Study Terminated by Sponsor 
X (XX.X%) 
 Treatment Limiting Toxicity (TLT) Event 
X (XX.X%) 
 Pregnancy 
X (XX.X%) 
 Other 
X (XX.X%) 
Reason for discontinuation from Extension Phase 
 Reason1 
X (XX.X%) 
 Reason2 
X (XX.X%) 
[1] Percentages are based on the number of all patients who signed the Informed Consent form.
[2] Percentages are based on the number of patients in the Safety Population.
SOURCE: Listing 16.2.1
Programming note: only present ‘Ongoing’ in Completion Status section if patient is still in active treatment phase.


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Table 14.1.2 
Summary of Protocol Deviations  
Safety Population 
 
Violation Level 
  COVID-19 Relatedness 
    Deviation Category 
Overall 
(N=X) [1] 
Number of Protocol Deviations 
n (%)  
 
 
 
Total number of protocol deviations reported 
<<Leave blank>> 
XXX (100.0%) 
 
 
 
Important [2] 
XXX 
XX (XX.X%) 
  Non COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Study Drug Compliance 
     X 
XX (XX.X%) 
    <<List all relevant Major categories>>…. 
     X 
XX (XX.X%) 
 
 
 
Important (CS) 
XXX 
XX (XX.X%) 
  Non COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Study Drug Compliance 
     X 
XX (XX.X%) 
    Procedure/Assessment Not Done/Done Incorrectly 
     X 
XX (XX.X%) 
    <<List all relevant Major CS categories>>…. 
     X 
XX (XX.X%) 
 
 
 
  COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Study Drug Compliance 
     X 
XX (XX.X%) 
    Visit Window 
     X 
XX (XX.X%) 
    Procedure/Assessment Not Done/Done Incorrectly 
     X 
XX (XX.X%) 
    <<List all relevant Major CS categories>>…. 
     X 
XX (XX.X%) 
 
 
 
Important (NCS) 
XXX 
XX (XX.X%) 
  Non COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Informed consent 
     X 
XX (XX.X%) 
    Procedure/Assessment Not Done/Done Incorrectly 
     X 
XX (XX.X%) 
    <<List all relevant Major NCS categories>>…. 
     X 
XX (XX.X%) 
 
 
 
  COVID-19 Deviation 
  XX 
XX (XX.X%) 
    Study Drug Compliance 
     X 
XX (XX.X%) 
    Visit Window 
     X 
XX (XX.X%) 
    Procedure/Assessment Not Done/Done Incorrectly 
     X 
XX (XX.X%) 
    <<List all relevant Major NCS categories>>…. 
     X 
XX (XX.X%) 
 
 
 
Non-Important 
XXX 
XX (XX.X%) 
  Non COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Informed consent 
     X 
XX (XX.X%) 
    Procedure/Assessment Not Done/Done Incorrectly 
     X 
XX (XX.X%) 
    <<List all relevant Minor categories>>…. 
     X 
XX (XX.X%) 
 
 
 
  COVID-19 Deviations 
  XX 
XX (XX.X%) 
    Study Drug Compliance 
     X 
XX (XX.X%) 
    Visit Window 
     X 
XX (XX.X%) 
    <<List all relevant Minor categories>>…. 
     X 
XX (XX.X%) 
 
 
 


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Abbreviations: CS = Clinically significant, NCS = Not clinically significant. 
Note: Percentage are based on the total number of protocol deviations (n) reported in the Safety Population.  
Note: N is the number of patient in the Safety Population. 
[1] Each patient is counted once per Violation Level and once per COVID-19 Relatedness, with patient being counted once within the Deviation Category, e.g., if patient had a procedure 
done incorrectly due to COVID-19 and also had a compliance issue due to COVID-19 both of which were classed as Important (CS) events, then the patient would have the following 
records: 1=Important (CS); 1=COVID-19 Deviations; 1=Study Drug Compliance and 1=Procedure… as patient’s entries. 
[2] Protocol deviation was not classified as CS or NCS at the time of the datacut. 
SOURCE: Listing 16.2.2.2 
 
Programming note: <<Leave blank>> cell in the shells should not be populated. Total number of ‘Deviation Categories’ present for one subject will not add up to the ‘COVID-19 
Relatedness’, it should be higher as accounts for each individual PD category while relatedness counts the patient once irrespective of now many individual PDs have occurred. 
If category is not present in the data, skip outputting to the table (mostly will refer to Important [2] once data is corrected). 
Identify COVID deviations using COVID19 variable. 
Present in descending count order of PDs, if ties present, sort alphabetically. 
 
 


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Table 14.1.3 
Demographics and Baseline Characteristics 
Safety Population 
Variable 
   Statistic or Category 
Overall 
(N=XX) 
 
 
Age (years) 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Gender 
 
   Male 
X (XX.X%) 
   Female 
X (XX.X%) 
 
 
Ethnicity 
 
   Hispanic or Latino 
X (XX.X%) 
   Not Hispanic or Latino 
X (XX.X%) 
 
 
Race 
 
   American-Indian or Alaska Native 
X (XX.X%) 
   Asian 
X (XX.X%) 
   Black or African-American 
X (XX.X%) 
   Native Hawaiian or Other Pacific Islander 
X (XX.X%) 
   White 
X (XX.X%) 
   Other 
X (XX.X%) 
 
 
Height (cm) 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Weight (kg) 
 
   n 
XX 
   Mean (SD) 
XX.X(XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Abbreviations: BMI = Body mass index; SD= Standard deviation. 
Note: Percentage are based on the number of patients in the Safety Population 
SOURCE: Listing 16.2.4.1


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Table 14.1.3 
Demographics and Baseline Characteristics 
Safety Population 
Variable 
   Statistic or Category 
Overall 
(N=XX) 
 
 
BMI (kg/m2) 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Capsule Strength Received 
 
   25 mg 
X (XX.X%) 
   100 mg 
X (XX.X%) 
 
 
Abbreviations: BMI = Body mass index; SD= Standard deviation. 
Note: Percentage are based on the number of patients in the Safety Population. 
SOURCE: Listing 16.2.4.1 
 


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Table 14.1.4 
Summary of Study Drug Exposure 
Safety Population 
Drug Exposure 
Overall 
(N=XX) 
Number of Doses Taken 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Treatment Duration (Days) [1] 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Total Study Drug Administerd (mg) 
 
   n 
XX 
   Mean (SD) 
XX.X (XX.XX) 
   Median 
XX.X 
   Min, Max 
XX, XX 
 
 
Intra Dose Escalation 
 
   50 mg to 100 mg 
X (XX.X%) 
   100 mg to 150 mg 
X (XX.X%) 
   150 mg to 200 mg 
X (XX.X%) 
   200 mg to 300 mg 
X (XX.X%) 
   300 mg to 400 mg 
X (XX.X%) 
 
 
Note: The data cut off date is used if study medication is ongoing (i.e., missing study medication end date in CRFs). A cut off date of XXMMMYYYY is used to calculate dose duration. 
[1] Duration = Date of last dose administered – Date of first dose administered + 1. 
SOURCE: Listing 16.2.4.4.1 
 
 


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Table 14.1.5 
Summary of Medical History 
Safety Population 
 
System Organ Class 
Preferred Term 
Overall 
(N=XX) 
 
 
 
Patients with at least one Medical History 
X (XX.X%) 
 
 
System Organ Class 1 
 
   Preferred Term 1 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
 
X (XX.X%) 
System Organ Class 2 
 
   Preferred Term 1 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
 
 
Note: Percentages are based on the number of patients in the Safety Population.  
Medications coded using WHO-DD B2E version March 2017.  
Medications are displayed by descending frequency of System Organ Class (SOC), by Preferred Term (PT) within SOC and then alphabetically. Patients were counted only once for 
each SOC and PT. 
SOURCE: Listing 16.2.4.2 
 
 
 


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Page 50 of 172 
Table 14.2.1.1 
Summary of AUCs and Mean of AUCs for ANC by Dose Level - AUCANC ≥ 600/µL Threshold 
Safety Population 
Visit/ 
  Statistics
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
300/400 mg 
(N=XX) 
   Week 5 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
      Median 
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
      Min, Max 
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
P-value
X.XXX
95% CI
[XX.X; XX.X] 
   Week 13 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
      Median 
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
      Min, Max 
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
P-value
X.XXX
95% CI
[XX.X; XX.X] 
   Week 21 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
      Median 
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
      Min, Max 
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
XX.X, XX.X
P-value
X.XXX
95% CI
[XX.X; XX.X] 
Abbreviations: AUC = Area under the plasma concentration; CI = Confidence interval; NE = Not estimable; SD = Standard deviation.  
Note: AUC is calculated using the trapezoidal rule with area above the threshold being positive and the area below the threshold being negative. The threshold is defined as 600 /ul 
for ANC. P-value is obtained from two-sided one sample t-test. 
[*] The summary is based on the mean of AUCs that is, the per-patient average of the AUCANC where patient was treated with at least 300/400mg dose. Missing AUCs are not imputed. 
For a given patient, if all 3 AUCs are missing then per-patient average is missing.  
[#] Extension Visits occur every 6 months from the EOS until the drug becomes commercially available. 
SOURCE: Listing 16.2.6.1 
Programming Note: P-value and 95% CI are computed only for 300/400mg dose, NOT for each dose level. 
For dose 300/400mg : "Mean AUC (cell.hr/uL) for ALC (cell/uL) - Weeks 5, 13, 21 - Dose 300 or 400" and "Mean AUC (cell.hr/uL) for ALC (cell/uL) - Extension Visits - Dose 300 or 
400". The first parameter will then be used for "All Visits" section and the 2nd parameter will be used for "Extension Visits" section. 


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Page 51 of 172 
Table 14.2.1.1 
Summary of AUCs and Mean of AUCs for ANC by Dose Level  
Safety Population 
Visit/ 
  Statistics 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
300/400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
All Visits[*] 
 
 
 
 
 
 
 
      n 
 
 
 
 
 
 
XX 
      Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
      Median 
 
 
 
 
 
 
XX.X 
      Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
      P-value 
 
 
 
 
 
 
X.XXX 
      95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
Extension Visits 
[#] 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
     P-value 
 
 
 
 
 
 
X.XXX 
     95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
Abbreviations: AUC = Area under the plasma concentration; CI = Confidence interval; NE = Not estimable; SD = Standard deviation.  
Note: AUC is calculated using the trapezoidal rule with area above the threshold being positive and the area below the threshold being negative. The threshold is defined as 500 /ul 
for ANC. P-value is obtained from two-sided one sample t-test. 
[*] The summary is based on the mean of AUCs that is, the per-patient average of the AUCANC where patient was treated with at least 300/400mg dose. Missing AUCs are not 
imputed. For a given patient, if all 3 AUCs are missing then per-patient average is missing.  
[#] Extension Visits occur every 6 months from the EOS until the drug becomes commercially available. 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. 
Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
SOURCE: Listing 16.2.6.1 
 
Programming Note: P-value and 95% CI are computed only for 300/400mg dose, NOT for each dose level. 
 
 


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Page 52 of 172 
Table 14.2.1.1.1 
Summary of AUCs and Mean of AUCs for ANC by Dose Level - AUCANC ≥ 500/µL Threshold 
Safety Population 
 
 
(Same shell as Table 14.2.1.1. Update footnote to: The threshold is defined as 600 /ul for ANC.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Page 53 of 172 
Table 14.2.1.2 
Summary of AUCs and Mean of AUCs for ALC by Dose Level  
Safety Population 
Visit/ 
  Statistics 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
300/400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
   Week 5 
 
 
 
 
 
 
 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
      Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
      Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
      P-value 
 
 
 
 
 
 
X.XXX 
      95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
   Week 13 
 
 
 
 
 
 
 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
      Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
      Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
      P-value 
 
 
 
 
 
 
X.XXX 
      95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
   Week 21 
 
 
 
 
 
 
 
      n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
      Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
      Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
      Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
      P-value 
 
 
 
 
 
 
X.XXX 
      95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
Abbreviations: AUC = Area under the plasma concentration; CI = Confidence interval; NE = Not estimable; SD = Standard deviation.  
Note: AUC is calculated using the trapezoidal rule with area above the threshold being positive and the area below the threshold being negative. The threshold is defined as 1000 /ul 
for ALC. P-value is obtained from two-sided one sample t-test. 
[*] The summary is based on the mean of AUCs that is, the per-patient average of the AUCALC where patient was treated with at least 300/400mg dose. Missing AUCs are not 
imputed. For a given patient, if all 3 AUCs are missing then per-patient average is missing.  
[#] Extension Visits occur every 6 months from the EOS until the drug becomes commercially available. 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. 
Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
SOURCE: Listing 16.2.6.1 
 
Programming Note: P-value and 95% CI are computed only for 300/400mg dose, NOT for each dose level. 
 
 


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Page 54 of 172 
Table 14.2.1.2 
Summary of AUCs and Mean of AUCs for ALC by Dose Level  
Safety Population 
Visit/ 
  Statistics 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
300/400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
All Visits[*] 
 
 
 
 
 
 
 
      n 
 
 
 
 
 
 
XX 
      Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
      Median 
 
 
 
 
 
 
XX.X 
      Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
      P-value 
 
 
 
 
 
 
X.XXX 
      95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
Extension Visits 
[#] 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
     P-value 
 
 
 
 
 
 
X.XXX 
     95% CI 
 
 
 
 
 
 
[XX.X; XX.X] 
 
 
 
 
 
 
 
 
Abbreviations: AUC = Area under the plasma concentration; CI = Confidence interval; SD = Standard deviation. 
Note: AUC is calculated using the trapezoidal rule with area above the threshold being positive and the area below the threshold being negative. The threshold is defined as 1000 /ul 
for ALC. P-value is obtained from two-sided one sample t-test. 
[*] The summary is based on the mean of AUCs that is, the per-patient average of the AUCALC where patient was treated with at least 300/400mg dose. Missing AUCs are not 
imputed. For a given patient, if all 3 AUCs are missing then per-patient average is missing.  
[#] Extension Visits occur every 6 months from the EOS until the drug becomes commercially available. 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. 
Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
SOURCE: Listing 16.2.6.1 
 
Programming Note: P-value and 95% CI are computed only for 300/400mg dose, NOT for each dose level. 
 
 


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Page 55 of 172 
 
Table 14.2.2.1 
Summary of Infection Rates 
Safety Population 
Note: XX (X.XX) [X.XX; X.XX] syntax refers to the number of infections – XX, followed by the infection rate (X.XX) and 95% CI [X.XX; X.XX]. 
Note: Percentages are based on number of patients in the Safety Population. Two-sided 95% CI is computed using the Normal approximation of the Negative Binomial Distribution. 
[1] Rate of infection, per year, is defined as the total number of infections divided by the total number of person-years. 
SOURCE: Listing 16.2.7.3 
 
 
Dose Levels 
 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Rate of Infection by type [1] 
 
 
 
 
 
 
 
    Number of events (Rate of  
Infection) by type 1 / [95% CI] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
    Number of events (Rate of Infection) 
type 2 / [95% CI] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
    ….. 
 
 
 
 
 
 
 
    Number of events (Rate of Infection) 
by type k / [95% CI] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
 
 
 
 
 
 
 
 
Number of events (Rate of All types of 
Infections) / [95% CI] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
XX (X.XX) 
[X.XX; X.XX] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Page 56 of 172 
Table 14.2.2.2 
Summary of Infections by Severity 
Safety Population 
Note: XX (X.XX) syntax refers to the number of infections – XX, followed by the infection rate (X.XX). 
Note: Percentages are based on number of patients in the Safety Population. Two-sided 95% CI is computed using the Normal approximation of the Negative Binomial Distribution. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
SOURCE: Listing 16.2.7.3 
 
Infections/ 
   Grade [1] 
Dose Levels 
 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least one Infection 
 
 
 
 
 
 
 
   Grade 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 4 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 5 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Infection 1 
 
 
 
 
 
 
 
   Grade 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 4 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 5 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Infection 2 
 
 
 
 
 
 
 
   Grade 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 4 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Grade 5 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Page 57 of 172 
Table 14.2.2.3 
Summary of Highest Grade Infections 
Safety Population 
Note: Percentages are based on number of patients in the Safety Population. 
Note: This table summarizes only infections which meet the highest severity grade criteria at the given dose level for each patient. An infection is considered to have met the criteria 
if the severity of infection is same as the maximum severity grade experienced by the patient at the given dose level. [1] The severity is assessed using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). 
SOURCE: Listing 16.2.7.3 
 
 
 
 
Infections/ 
Grade [1] 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
Patients with at least one Infection 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Infection 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Infection 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.2.4 
Summary of Infection Scores 
Safety Population 
Statistics 
X4P-001 
50/100/150 mg 
(N=XX) 
X4P-001 
200 mg 
(N=XX) 
X4P-001 
300 mg 
(N=XX) 
X4P-001 
400 mg 
(N=XX) 
X4P-001 
300/400 mg 
(N=XX) 
Overall Infection Score [1] 
   Number of Infection Events 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
   Standard Error 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
   Median 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
   Min, Max 
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
   95% CI 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
Note: Percentages are based on number of patients in the Safety Population. Two-sided 95% CI is computed using the Normal Distribution. 
Note: n is the number of patients who had an infection whilst on the reported dose of the study drug. 
[1] Infection Score = (# of infection events × severity) / duration of exposure in years.
SOURCE: Listings 16.2.7.1 and 16.2.7.3
Programming note: use OINFSC from ADIR dataset. 
n is the number of patients who had an event while on IMP dose at the time. 


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Page 59 of 172 
Table 14.2.3.1 
Summary of Non-Genital Warts 
Safety Population 
 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
Note: An out of schedule assessment of warts was done at end of study visit for subject 
. 
SOURCE: Listing 16.2.4.5. 
Study Week/ 
   Statistic 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
Confidential 
 
 
 
 
 
Page 60 of 172 
Table 14.2.3.1 
Summary of Non-Genital Warts 
Safety Population 
 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
Note: An out of schedule assessment of warts was done at end of study visit for subject 
. 
SOURCE: Listing 16.2.4.5 
 
 
Study Week/ 
   Statistic 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension visits 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Page 61 of 172 
Table 14.2.3.2 
Summary of Non-Genital Warts by location 
Safety Population 
Location: XXXXXX 
 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
Note: An out of schedule assessment of warts was done at end of study visit for subject 
. 
SOURCE: Listing 16.2.4.5. 
Study Week/ 
Statistic 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Confidential 
 
 
 
 
 
Page 62 of 172 
Table 14.2.3.2 
Summary of Non-Genital Warts by location 
Safety Population 
Location: XXXXXX 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
Note: An out of schedule assessment of warts was done at end of study visit for subject 
. 
SOURCE: Listing 16.2.4.5 
 
 
Study Week/ 
   Statistic 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension visits 
 
 
 
 
 
 
 
     n 
 
 
 
 
 
 
XX 
     Mean (SD) 
 
 
 
 
 
 
XX.X (XX.XX) 
     Median 
 
 
 
 
 
 
XX.X 
     Min, Max 
 
 
 
 
 
 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Confidential 
 
 
 
 
 
Page 63 of 172 
Table 14.2.4.1 
Summary of Genital Warts 
Safety Population 
 
(Same shell as Table 14.2.3: SOURCE: Listing 16.2.4.5) 
 


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Page 64 of 172 
Table 14.2.5 
Summary of Antibody Levels following Revaccination 
Safety Population 
Antibodies: Haemophilus Influenzae B Polysaccharide (mg/L) 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded on or before treatment start date. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.4.6. 
 
Study Week / 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 9 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 9 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 17 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 17 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Page 65 of 172 
Table 14.2.5 
Summary of Antibody Levels following Revaccination 
Safety Population 
Antibodies: <<parameter>> 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded on or before treatment start date. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.4.6 
 
Study Week /  
   Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
CFB to Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Page 66 of 172 
Table 14.2.6 
Summary of Rescue Medications 
Safety Population 
 
ATC Class Level 4 
Preferred Term (ATC Class Level 5) 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least one Rescue  
Medication 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
ATC Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
ATC Class 2 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Note: Percentages are based on the number of patients in the Safety Population.  
Medications coded using WHO-DD B2E version March 2017.  
Medications are displayed by descending frequency of Anatomic Therapeutic Chemical (ATC) Level 4 classification, by Preferred Term (PT) within ATC and then alphabetically. 
Patients were counted only once for each ATC and PT. 
SOURCE: Listing 16.2.9.1 
 


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Page 67 of 172 
Table 14.2.7 
Summary of Hospitalizations 
Safety Population 
 
 
Hospitalization 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Hospitalized 
 
 
 
 
 
 
 
   Yes 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   No 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Hospitalized WHIM Related  
 
 
 
 
 
 
 
  Yes 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   No 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Hospitalized AE Related 
 
 
 
 
 
 
 
  Yes 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  No 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Total Number of hospitalizations 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Duration of hospitalization (in Days) 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; NE = Not estimable; SD = Standard deviation. 
Note: Percentages are based on the number of patients in the Safety Population.  
SOURCE: Listing 16.2.7.1, 16.2.7.3 
 
 


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Page 68 of 172 
Table 14.2.8 
Summary of Ig and Specified Antibodies 
Safety Population 
Antibody: XXXXXXX   
Abbreviations: CFB Change from Baseline; NE = Not estimable; SD = Standard deviation. 
Note: Change is calculated as post baseline - baseline. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.8.4 
Study Week/ 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 2 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 3 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 3 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Table 14.2.8 
Summary of Ig and Specified Antibodies 
Safety Population  
 
Antibody: XXXXXXX  
 
Abbreviations: CFB Change from Baseline; NE = Not estimable; SD = Standard deviation. 
Note: Change is calculated as post baseline - baseline. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.8.4 
 
 
Study Week/ 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
CFB to Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 


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Table 14.2.9 
Time above Threshold (Hours) for ANC by Dose Level 
Safety Population 
Statistics 
X4P-001 
50/100/150 mg 
(N=XX) 
X4P-001 
200 mg 
(N=XX) 
X4P-001 
300 mg 
(N=XX) 
X4P-001 
400 mg 
(N=XX) 
X4P-001 
300/400 mg 
(N=XX) 
Number of Subjects 
XX 
XX 
XX 
XX 
XX 
Mean (SD) 
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
XX.XX (XX.XXX)
Standard Error 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Median 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Min, Max 
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
Abbreviation: SD = Standard deviation. 
Note: Time above threshold is defined as total time a subjects ANC result was above 500/uL. If time above threshold was >24 hours, it was rounded off to 24. Baseline observation 
carried forward (BOCF) imputation was used if a subjects 24 hour assessment was missing. Imputation is not used for intermediate missing assessments.  
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. 
Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
Dense sample data for subject 
 will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening. 
SOURCE: Listing 16.2.6.2.3 
Table 14.2.9.1 
Time above Threshold (Hours) for ANC by Dose Level – Sensitivity Analysis 
Safety Population 
(Same shell as Table 14.2.9: SOURCE: Listing 16.2.6.2.3. Do not display the footnote ‘Dense sample data for subject 
will be excluded from the TAT summary tables and 
figures since the WBC, ANC, ALC, and AMC levels were normal at screening.’) 
  Table 14.2.10 
Time above Threshold (Hours) for ALC by Dose Level 
Safety Population 
(Same shell as Table 14.2.9: SOURCE: Listing 16.2.6.2.3) 
Programming Note: Use ALC instead of ANC in the footnote and use threshold as 1000/uL. 


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  Table 14.2.10.1 
Time above Threshold (Hours) for ALC by Dose Level – Sensitivity Analysis 
Safety Population 
 
(Same shell as Table 14.2.9: SOURCE: Listing 16.2.6.2.3 Do not display the footnote. ‘Dense sample data for subject 
 will be excluded from the TAT summary tables and 
figures since the WBC, ANC, ALC, and AMC levels were normal at screening.’) 
 
 
 
 
 
 
Table 14.2.11 
Time above Threshold (Hours) for AMC by Dose Level  
Safety Population 
 
(Same shell as Table 14.2.9: SOURCE: Listing 16.2.6.2.3) 
 
Programming Note: Use AMC instead of ANC in the footnote and use threshold and categorize by age ranges; 12-18yrs and >=18yrs, and gender; Male and Female as follows:  
Age (year) 
Gender 
Threshold (/uL) 
12-18 
F 
190 
 
M 
180 
>=18 
F 
250 
 
M 
290 
 
Add footnote: 
Note: Time above threshold is defined as total time a subject's AMC result was above 190/uL for females aged 12 to 18, above 180/uL for males aged 
12 to 18, above 250/uL for females aged>=18 and above 290/uL for males aged >=18. If time above threshold was >24 hours, it was rounded off to 24. Baseline observation carried fo
rward (BOCF) imputation was used if a subject's 24 hour assessment was missing. Imputation is not used for intermediate missing assessments. 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. 
Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
Dense sample data for subject 
 will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening. 
SOURCE: Listing 16.2.6.2.3 
 
 
Table 14.2.11.1 
Time above Threshold (Hours) for AMC by Dose Level – Sensitivity Analysis 
Safety Population 
 
(Same shell as Table 14.2.11: SOURCE: Listing 16.2.6.2.3. Do not display the footnote ‘Dense sample data for subject 
 will be excluded from the TAT summary tables 
and figures since the WBC, ANC, ALC, and AMC levels were normal at screening.’) 
 
 
 
 
 
 


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Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Population 
 
 
Treatment-Emergent Adverse 
Events 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least one TEAE  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%)  
X (XX.X%)  
X (XX.X%)  
 
 
 
 
 
 
 
 
 
Total Number of Events 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
TEAE by Relationship [2] 
 
 
 
 
 
 
 
 
      Unrelated 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
      Related 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
AE leading to Discontinuation from  
study 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
AE leading to Death 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; SAE = Serious AE; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). “All Grades” includes all TEAEs with CTCAE 
Grade 1 to 5, “≥ Grade 3” is a subset of “All Grades” reported. 
[2] Unrelated TEAEs are those marked as not related on the case report form (CRF); Related TEAEs are those marked as possibly related or related on the CRF. 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Population 
 
 
Treatment-Emergent Adverse Events 
Dose Levels 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
Overall 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least one TEAE  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Total Number of Events 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
TEAE by Relationship [2] 
 
 
 
 
 
 
      Unrelated 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
      Related 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
AE leading to Discontinuation from study 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
AE leading to Death 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; SAE = Serious AE; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). “All Grades” includes all TEAEs with CTCAE 
Grade 1 to 5, “≥ Grade 3” is a subset of “All Grades” reported. 
[2] Unrelated TEAEs are those marked as not related on the case report form (CRF); Related TEAEs are those marked as possibly related or related on the CRF. 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.1.2 
Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
 
System Organ Class 
   Preferred Term 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.1.2 
Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
 
System Organ Class 
   Preferred Term 
Dose Levels 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
Overall 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug though 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
SOURCE: Listing 16.2.7.1 


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Table 14.3.1.3 
Summary of Treatment-Emergent Adverse Events Related to Study Treatment by System Organ Class and Preferred Term 
Safety Population 
 
TEAEs Related to Study Drug** 
System Organ Class 
   Preferred Term 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
** A related TEAE is one that is marked as possibly related, probably related, or definitely related as assessed by the Investigator. 
SOURCE: Listing 16.2.7.1 


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Table 14.3.1.3 
Summary of Treatment-Emergent Adverse Events Related to Study Treatment by System Organ Class and Preferred Term 
Safety Population 
 
TEAEs Related to Study Drug**  
System Organ Class 
   Preferred Term 
Dose Levels 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
Overall 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One TEAE Related to 
Study Drug 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug though 10 days after the last dose of the study drug. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
** A related TEAE is one that is marked as possibly related, probably related, or definitely related as assessed by the Investigator. 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.2.1 
Summary of Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Abbreviations: SAE = Serious adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. SAEs were coded using MedDRA version 23.1.  
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
SOURCE: Listing 16.2.7.1 
 
 
 
System Organ Class 
   Preferred Term 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 


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Page 79 of 172 
Table 14.3.2.1 
Summary of Serious Adverse Events by System Organ Class and Preferred Term  
Safety Population 
 
System Organ Class 
   Preferred Term 
Dose Levels 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
Overall 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Abbreviations: SAE = Serious adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. SAEs were coded using MedDRA version 23.1.  
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
SOURCE: Listing 16.2.7.1 


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Table 14.3.2.2 
Summary of Serious Adverse Events Related to Study Treatment by System Organ Class and Preferred Term 
Safety Population 
 
SAEs Related to Study Drug** 
System Organ Class 
   Preferred Term 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
 
 
 
 
 
 
 
 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
 
 
 
 
 
 
 
 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: SAE = Serious adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. SAEs were coded using MedDRA version 23.1. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). 
** A related SAE is one that is possibly related, probably related, or definitely related as assessed by the Investigator. 
SOURCE: Listing 16.2.7.1 
 
 


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Page 81 of 172 
Table 14.3.2.2 
Summary of Serious Adverse Events Related to Study Treatment  
by System Organ Class and Preferred Term 
Safety Population 
 
SAEs Related to Study Drug** 
System Organ Class 
   Preferred Term 
Dose Levels 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
Overall 
(N=XX) 
 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
All Grades[1] 
≥ Grade 3[1] 
Patients with at least One SAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
Abbreviation: SAE = Serious adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. 
SAEs were coded using MedDRA version 23.1. 
[1] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). 
** A related SAE is one that is possibly related, probably related, or definitely related as assessed by the Investigator. 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.2.3 
Summary of Treatment-Limiting Toxicities by System Organ Class and Preferred Term 
Safety Population 
 
 
System Organ Class 
   Preferred Term 
Dose Levels 
 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least One TLT TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Abbreviations: TLT = Treatment-limiting toxicity; TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population.TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of the study drug. 
SOURCE: Listing 16.2.7.5 
 
 


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Table 14.3.2.4 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
   Preferred Term 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least One Grade 3 or 
Higher TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: TEAE = Treatment emergent adverse event. 
Note: Percentages are based on the number of patients in the Safety Population. N under each dose level represents patients who got drug at that dose level. TEAEs were coded 
using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of study drug. 
SOURCE: Listing 16.2.7.1 


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Page 84 of 172 
Table 14.3.2.5 
Rate of Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
   Preferred Term 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least One TEAE 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
System Organ Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
   Preferred Term 2 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
   Preferred Term 3 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
 
 
 
 
 
 
 
 
System Organ Class 2 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
   Preferred Term 1 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
   Preferred Term 2 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
   Preferred Term 3 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
X (XX.X) 
[X.XX, X.XX] 
 
 
 
 
 
 
 
 
Abbreviation: AE = Adverse event; CI = Confidence interval; TEAE = Treatment emergent adverse event. 
Note: XX (X.XX) [X.XX; X.XX] syntax refers to the number of TEAEs – XX, followed by the TEAE rate (X.XX) and 95% CI [X.XX; X.XX]. 
Percentages are based on the number of patients in the Safety Population. TEAEs were coded using MedDRA version 23.1.  
A TEAE is defined as any AE that begins or worsens in severity or frequency on or after the start of study drug through 10 days after the last dose of study drug. 
TEAE rate is the total number of TEAEs at that dose, divided by the total time (in years) all patients were treated at that dose. Two-sided 95% CI is computed using the Negative 
Binomial Distribution. 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.2.6.1 
Summary of Yearly Infection Rate for Subjects on 300mg and 400mg Dose Levels by 6 Month Intervals 
Safety Population 
Period 
   Rate Statistics 
X4P-001 
300/400 mg 
(N=XX) 
Pre-Study (12 months prior to first dose) 
   Number of Infection Events 
XX 
   Mean (SD) 
XX.XX (XX.XXX)
   Standard Error 
XX.XX
   Median 
XX.XX
   Min, Max 
XX.X, XX.X
   95% CI 
(XX.XX, XX.XX) 
0-6 Months
Number of Infection Events
XX 
Mean (SD)
XX.XX (XX.XXX)
Standard Error
XX.XX
Median
XX.XX
Min, Max
XX.X, XX.X
95% CI
(XX.XX, XX.XX) 
… 
Abbreviation: CI = Confidence interval; NE = Not estimable; SD = Standard deviation. 
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”. The reporting period starts on the 300 mg dose date. Rate is defined as number of 
infection events in a given period/duration of period in years. 95% CI is based on normal approximation. Only events with start date occurring within start and end dates of 300/400 mg 
dose for each subject are included. Time period assignment is based on the start date of the event.  
SOURCE: Listing 16.2.7.6 
Programming Note: Complete table until maximum duration in 6 month intervals 
For Pre-study infection rate use ADIR.PARAMCD=PINFRATE 
For 0-6 months, ADIR.PARAMCD=OINFRTBP and DOSEA in (300,400) and ETINFG1=0 – 6 Months. 
For 6-12 months, ADIR.PARAMCD=OINFRTBP and DOSEA in (300,400) and ETINFG1=6 – 12 Months 
Continue for all available data…. 
For 0-6 months, for Number of infection events- ADIR.NOINFBP and DOSEA in (300,400) and ETINFG1=0 – 6 Months. 
For 6-12 months, for Number of infection events- ADIR.NOINFBP and DOSEA in (300,400) and ETINFG1=6 – 12 Months 
Continue for all available data ….


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Page 86 of 172 
Table 14.3.2.6.2 
Summary of Yearly Infection Score for Subjects on 300mg and 400mg Dose Levels by 6 Month Intervals 
Safety Population 
Period 
   Infection Score Statistics [1] 
X4P-001 
300/400 mg 
(N=XX) 
0-6 Months
Number of Infection Events
XX 
Mean (SD)
XX.XX (XX.XXX)
Standard Error
XX.XX
Median
XX.XX
Min, Max
XX.X, XX.X
…95% CI 
(XX.XX, XX.XX) 
6-12 Months
Number of Infection Events
XX 
Mean (SD)
XX.XX (XX.XXX)
Standard Error
XX.XX
Median
XX.XX
Min, Max
XX.X, XX.X
…95% CI 
(XX.XX, XX.XX) 
… 
Abbreviation: CI = Confidence interval; NE = Not estimable; SD = Standard deviation. 
Notes: Infections are identified as follows: On study infections are identified as all events with a MedDRA System Organ Class of “Infections and infestations”. The reporting period 
starts on the 300 mg dose date. Only events with start date occurring within start and end dates of 300/400 mg dose for each patient are included. Time period assignment is based on 
the start date of the event.  
[1] Infection Score = (# of infection events × severity) / duration of period in years.
SOURCE: Listing 16.2.7.6
Programming Note: Exposure in years is constant in this table, at 6 month intervals, so exposure is always 0.5. 
For number of infection events, use PARAMCD=NOINFBP 
Complete table until maximum duration in 6 month intervals up to last available interval 
For 0-6 months Infection Score, ADIR.PARAMCD=OINFSCBP and DOSEA in (300,400) and ETINFG1=0–6 Months. 
For 6-12 months Infection Score, ADIR.PARAMCD= OINFSCBP and DOSEA in (300,400) and ETINFG1=6–12 Months 
Continue for all available data …. 


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Table 14.3.2.7.1 
Summary of Yearly Infection Rate by Dose Level – Method 1 
Safety Population 
Rate 
Statistics 
12 Months 
Prior to 
First Dose 
(N=XX) 
X4P-001 
50 mg 
(N=XX) 
X4P-001 
100 mg 
(N=XX) 
X4P-001 
150 mg 
(N=XX) 
X4P-001 
50/100/150 mg 
(N=XX) 
X4P-001 
200 mg 
(N=XX) 
X4P-001 
300 mg 
(N=XX) 
X4P-001 
400 mg 
(N=XX) 
X4P-001 
300/400 mg 
(N=XX) 
 Number of 
Infection 
Events 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 Mean (SD) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
 Standard 
Error 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
 Median 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
 Min, Max 
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
 95% CI 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
Abbreviations: CI = Confidence interval; NE = Not estimable; SD = Standard deviation. 
Notes: On study infections are identified as all events with a MedDRA System Organ Class of “Infections and infestations”. Infection rate is calculated as the total number of infection 
events for all patients within each dose level ÷ total duration of exposure (in years) for all patient within each dose level.  95% CI and Standard Error are based on Poisson 
approximation for each dose level. Events at dose level are assigned based on the start date of the event occurring within start and end dates of that dose for each subject. 
SOURCE: Listing 16.2.7.7 
Programming Note: For Rate use ADIR.PARAMCD=OINFRAT1. 


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Page 88 of 172 
Table 14.3.2.7.2 
Summary of Yearly Infection Rate by Dose Level – Method 2 
Safety Population 
Rate 
Statistics 
12 Months 
Prior to 
First Dose 
(N=XX) 
X4P-001 
50 mg 
(N=XX) 
X4P-001 
100 mg 
(N=XX) 
X4P-001 
150 mg 
(N=XX) 
X4P-001 
50/100/150 mg 
(N=XX) 
X4P-001 
200 mg 
(N=XX) 
X4P-001 
300 mg 
(N=XX) 
X4P-001 
400 mg 
(N=XX) 
X4P-001 
300/400 mg 
(N=XX) 
 Number of 
Infection 
Events 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 Mean (SD) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
XX.XX
(XX.XXX) 
 Standard 
Error 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
 Median 
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
 Min, Max 
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
XX.X,XX.X
 95% CI 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
(XX.XX,XX.XX) 
Abbreviations: CI = Confidence interval; NE = Not estimable; SD = Standard deviation. 
Notes: On study infections are identified as all events with a MedDRA System Organ Class of “Infections and infestations”. Infection rate is calculated as: for each patient calculate the 
infection rate for each dose level, then calculate the average for all patients for each dose level. 95% CI is based on normal approximation. Events at dose level are assigned based on 
the start date of the event occurring within start and end dates of that dose for each subject. 
SOURCE: Listing 16.2.7.7 
Programming Note: For Rate use ADIR.PARAMCD=OINFRAT2. 


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Page 89 of 172 
Table 14.3.3.1 
Listing of Serious Adverse Events 
Safety Population 
 
Subject 
Number 
Dose 
Level 
(mg) 
Gender 
Age 
System Organ Class/ 
 Preferred Term/ 
  Verbatim Term 
Start Date/Time (Day)/ 
End Date/Time (Day)[1] 
Severity/ 
Causality [2] 
Outcome/ 
Action Taken 
200  
Male 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 4/ 
Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
400  
Female 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 3/ 
Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
200  
Female 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 2/ 
Not Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
 
Note: Adverse events were coded using MedDRA version 23.1. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). 
SOURCE: Listing 16.2.7.1 
 


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Table 14.3.3.2 
Listing of Treatment Emergent Adverse Events Leading to Discontinuation 
Safety Population 
 
Subject 
Number 
Dose 
Level (mg) 
Gender 
Age 
System Organ Class/ 
 Preferred Term/  
  Verbatim Term 
Start Date/Time (Day)/ 
End Date/Time (Day) [1] 
Severity/  
Causality [2] 
Outcome/ 
Action Taken 
200  
Male 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 4/ 
Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
400  
Female 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 3/ 
Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
200  
Female 
xx 
xxxx/ xxxx/ xxxx 
DDMMMYYYY/HH:MM (XX)/ 
DDMMMYYYY/HH:MM (XX) 
Grade 2/ 
Not Related 
XXX/ 
XXX 
 
 
 
 
 
 
 
 
Note: Adverse events were coded using MedDRA version 23.1.  
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03). 
SOURCE: 16.2.7.1 
 
 


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Table 14.3.4.1 
Listing of Out of Reference Range Laboratory Values 
Safety Population 
 
Subject 
Number 
Age 
Gender 
Lab Parameter 
Reference 
Range 
Dose Level  
(mg) 
 
Visit 
Date/Time of Collection 
(Day) [1] 
Parameter 
Value 
Test Result 
Assessment 
 
Male 
Hemoglobin 
XX-XX 
200  
xxxx 
DDMMMYYYY:HH:MM (XX) 
XX 
LOW 
 
 
 
 
 
 
 
 
 
 
Female 
Hemoglobin 
XX-XX 
400  
xxxx 
DDMMMYYYY:HH:MM (XX) 
XX 
HIGH 
 
 
 
 
 
 
 
 
 
 
Female 
Haematocrit 
XX-XX 
200  
xxxx 
DDMMMYYYY:HH:MM (XX) 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug.  
SOURCE: Listings 16.2.8.1, 16.2.8.2, 16.2.8.3, 16.2.8.6, 16.2.8.7 
 
 


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Table 14.3.5.1.1 
Summary of Actual and Change from Baseline in Hematology Results  
Safety Population 
Parameter: XXXXXXX   
Abbreviation: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
 
SOURCE: Listing 16.2.8.2 
Study Week/ 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 2 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 3 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 3 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Page 93 of 172 
 
Table 14.3.5.1.1 
Summary of Actual and Change from Baseline in Hematology Results  
Safety Population 
Parameter: XXXXXXX   
 
Abbreviation: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.8.2 
Programming Note: Repeat for ALL hematology parameters 
 
 
Study Week/ 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
CFB to Week 25 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 


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Table 14.3.5.1.2 
Shift from Baseline in Hematology Results 
Safety Population 
 
Parameter: XXXXXX; Dose level: XXX mg 
Note: Data are presented by parameter and dose. 
SOURCE: Listing 16.2.8.2 
Programming Note: Repeat table for ALL hematology parameters. 
Repeat table for 100 mg, 150 mg, 200 mg, 300 mg, 400 mg and Overall. 
 
 
Study Week/   
    Categories 
Baseline 
Total 
Low 
Normal 
High 
Missing 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
     Low 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Normal  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     High 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Total 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
Week 3 
 
 
 
 
 
     Low 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Normal  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     High 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Total 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
… 
 
 
 
 
 
Week 25 
 
 
 
 
 
     Low 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Normal  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     High 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Total 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
     Low 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Normal  
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     High 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
     Total 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 


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Table 14.3.5.2.1 
Summary of Actual and Change from Baseline in Serum Chemistry Results 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.8.1) 
 
 
 
 
Table 14.3.5.2.2 
Shift from Baseline in Serum Chemistry Results 
Safety Population 
 
(Same shell as Table 14.3.5.1.2: SOURCE: Listing 16.2.8.1) 
 
 
 
 
Table 14.3.5.3.1 
Summary of Actual and Change from Baseline in Coagulation Results 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.8.6) 
 
 
 
 
Table 14.3.5.3.2 
Shift from Baseline in Coagulation Results 
Safety Population 
 
(Same shell as Table 14.3.5.1.2: SOURCE: Listing 16.2.8.6) 
 
 
Table 14.3.5.4.1 
Summary of Actual and Change from Baseline in Cytometry Results 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.8.8, add footnote: Note: Each sample was run 3 times producing triplicate results A, B, C  for each laboratory test. 
 
 
 
Table 14.3.6.1.1 
Summary of Actual and Change from Baseline in Vital Signs 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.9.2) 
 
 
 


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Page 96 of 172 
Table 14.3.6.2.1 
Summary of Actual and Change from Baseline of 12-Lead Electrocardiogram (ECG) Parameters 
Safety Population 
ECG Parameter: XXXXX 
Abbreviations: CFB = Change from Baseline; NE = Not estimable; SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
 
 
 
Study Week /  
    Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 5 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Week 13 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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SOURCE: Listing 16.2.9.3. 
 
Table 14.3.6.2.1 
Summary of actual and Change from Baseline of 12-Lead Electrocardiogram (ECG) Parameters 
Safety Population 
ECG Parameter: XXXXX 
Abbreviations: CFB = Change from Baseline; NE = Not estimable, SD = Standard deviation. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
 
SOURCE: Listing 16.2.9.3. 
 
Study Week / 
Statistics 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
CFB to Week 21 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
CFB to Extension Visits 
 
 
 
 
 
 
 
     n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
     Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
     Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
     Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 


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Table 14.3.6.3.1 
Summary of Ophthalmologic Examination Results (Local Reader) 
Safety Populaion 
Abbreviations: CS = Clinically significant; NCS = Not clinically significant. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
 
SOURCE: Listing 16.2.9.5 
 
 
Study Week  
  Category 
Dose Levels 
Overall 
(N=X) 
50 mg 
(N=X) 
100 mg 
(N=X) 
150 mg 
(N=X) 
200 mg 
(N=X) 
300 mg 
(N=X) 
400 mg 
(N=X) 
 
 
 
 
 
 
 
 
Baseline [1] 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  Normal 
 
 
 
 
 
 
 
  Abnormal - CS 
 
 
 
 
 
 
 
  Abnormal - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
  Normal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  Abnormal - CS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  Abnormal - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Week 25 EOT 
 
 
 
 
 
 
 
  Normal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  Abnormal - CS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
  Abnormal - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.6.3.2 
Summary of Ophthalmologic Examination Results (Central Retinal Findings) 
Safety Populaion 
Abbreviations: CS = Clinically significant; NCS = Not clinically significant. 
[1] Baseline is the last non-missing observation recorded before the first dose on Day 1. Baseline visit is displayed for all dose levels irrespective of whether they were receiving that 
dose level at baseline. 
SOURCE: Listing 16.2.9.6 
Programming Note: Repeat for other body systems  
 
 
Study Week/ 
   Categories 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
 
   Normal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - CS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Central Retinal Exam Review Not Performed 
Due to Inadequacy of Retinal Photographs 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
   Normal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - Unchanged from Baseline 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - CS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Central Retinal Exam Review Not Performed 
Due to Inadequacy of Retinal Photographs 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
Week 25 EOT 
 
 
 
 
 
 
 
   Normal 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - Unchanged from Baseline 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - NCS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Abnormal - New Finding - CS 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Central Retinal Exam Review Not Performed 
Due to Inadequacy of Retinal Photographs 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.6.4 
Summary of Concomitant Medications  
Safety Population 
 
ATC Class Level 4 
   Preferred Term (ATC Class Level 5) 
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least one Prior 
Medication 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
ATC Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
ATC Class 2 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentages are based on the number of patients in the Safety Population.  
Medications coded using WHO-DD B3 version September 2020.  
Concomitant medications are medications taken or ongoing after the date of the first dose of study drug.  
Medications are displayed by descending frequency of Anatomic Therapeutic Chemical (ATC) Level 4 classification, by Preferred Term (PT) within ATC and then alphabetically. 
Patients were counted only once for each ATC and PT, 
SOURCE: Listing 16.2.9.1 
 
 


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Table 14.3.6.5.1 
Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and Imiquamod – Concomitant Medications 
Safety Population 
 
ATC Class Level 4 
   Preferred Term  
Dose Levels 
Overall 
(N=XX) 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
 
Patients with at least one Infection Medication 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
ATC Class 1 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
ATC Class 2 
 
 
 
 
 
 
 
   Preferred Term 1 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 2 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
   Preferred Term 3 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
X (XX.X%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Percentages are based on the number of patients in the Safety Population.  
Medications coded using WHO-DD B3 version September 2020.  
Concomitant medications are medications taken or ongoing after the date of the first dose of study drug.  
Medications are displayed by descending frequency of Anatomic Therapeutic Chemical (ATC) Level 4 classification, by Preferred Term (PT) within ATC and then alphabetically. 
Patients were counted only once for each ATC and PT. 
SOURCE: Listing 16.2.9.1 
 
 
 
 
Table 14.3.6.5.2 
Summary of Use of Antibiotics, G-CSF, Immunoglobulins, and Imiquamod – Prior Medications 
Safety Population 
 
(Same shell as Table 14.3.6.5.1: SOURCE: Listing 16.2.9.1. Update footnote to reference prior medications instead of concomitant medications: Prior medication is any 
medication that is started or ended prior to the first dose of the study medication) 
  
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.6.6 
Summary of Actual and Change from Baseline in SF-36 QOL Scores 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.9.8) 
 
 
Table 14.3.6.6 
Summary of Actual and Change from Baseline in HPV Impact Profile (HIP) Questionnaire - Domain Scores 
Safety Population 
 
(Same shell as Table 14.3.5.1.1: SOURCE: Listing 16.2.9.9.2) 
 
 


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Page 103 of 172 
Table 14.4.1 
Summary of Plasma X4P-001 Concentrations by Dose Level  
Safety Population 
 
 
Time Point 
   Statistic 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
Predose 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
30 mins post dose 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
24 hrs post dose 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
Abbreviations: CV = Coefficient of variation; NE = Not estimable; SD = Standard deviation. 
Note: measurements were made predose and at 30, 60, 90 mins and 2, 3, 4, 8, 12, 16 and 24 hrs post-dose. Unit of plasma X4P-001 concentrations is ng/mL. 
SOURCE: Listing 16.2.5.1 
Programming Note: Repeat table for all relevant visits. 
 
 


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Page 104 of 172 
Table 14.4.2 
Summary of Plasma X4P-001 Pharmacokinetic Parameters by Dose Level  
Safety Population 
  
Study Week: Week 5 
 
Parameter 
   Statistic 
Dose Levels 
50 mg 
(N=XX) 
100 mg 
(N=XX) 
150 mg 
(N=XX) 
200 mg 
(N=XX) 
300 mg 
(N=XX) 
400 mg 
(N=XX) 
 
 
 
 
 
 
 
AUC Over Dosing Interval (h*ng/mL) 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean [95%CI] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
CMax (ng/mL) 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean [95%CI] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
Time of CMax (h) 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Geometric Mean [95%CI] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
XX.X  
[XX.X; XX.X] 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min, Max 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  %CV 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
Note: As some subjects provided multiple values for the same dose level, median values were taken at the same dose level for each subject, the median values were then used in the 
analysis. 
Abbreviations: AUC = Area under the plasma concentration; CV = Coefficient of variation; NE = Not estimable; SD = Standard deviayion. 
SOURCE: Listings 16.2.5.1, 16.2.5.2 
 
Programming Note: Repeat table for all applicable visits. 
 


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Page 105 of 172 
14.3. 
Planned Figure Shells 
Figure 14.4.1.1 
WBC over Time by Patient 
Safety Population 
 
 
Y-axis: Leukocytes (10^9/L) 
X-axis: Weeks Since First Study Treatment 
*Value obtained during infection and considered to be confounded. 
SOURCE: Listing 16.2.8.2 
 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
 
Figure 14.4.1.2a 
ANC over Time by Patient 
Safety Population 
 
Header: Patient ID = XXX-XXX 
Y-axis: ANC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of baseline observation carried forward (BOCF) is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of 
the clinic resulting in the site not getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before 
were replaced with these samples. Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the 
assessment on 20FEB2018 at 9:25 was used as time 0.  
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. 
Dense sample data for subject 
 will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to 
splenectomy. 
 
*Value obtained during infection and considered to be confounded. 
SOURCE: Listing 16.2.6.1 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
 
Figure 14.4.1.2b 
ANC over Time by Dose Level 
Safety Population 
 
Header: Treatment Level (mg) = XXX 
Y-axis: ANC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of baseline observation carried forward (BOCF) is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of 
the clinic resulting in the site not getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before 
were replaced with these samples. Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the 
assessment on 20FEB2018 at 9:25 was used as time 0.  


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Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy. 
SOURCE: Listing 16.2.6.1 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
Figure 14.4.1.3a 
ALC over Time by Patient 
Safety Population 
 
Header: Patient ID = XXX-XXX 
Y-axis: ALC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of BOCF is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not 
getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before were replaced with these samples. 
Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was 
used as time 0. Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were 
excluded from the analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 
will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy. 
*Value obtained during infection and considered to be confounded. 
SOURCE: Listing 16.2.6.1 
 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
 
 
 
Figure 14.4.1.3b 
ALC over Time by Dose Level 
Safety Population 
 
Header: Treatment Level (mg) = XXX 
Y-axis: ALC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of BOCF is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not 
getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before were replaced with these samples. 
Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was 
used as time 0. Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were 
excluded from the analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 
will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy. 
SOURCE: Listing 16.2.6.1 
 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
 
Figure 14.4.1.4a 
Monocytes over Time by Patient 
Safety Population 


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Header: Patient ID = XXX-XXX 
Y-axis: AMC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of BOCF is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not 
getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before were replaced with these samples. 
Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was 
used as time 0.  Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were 
excluded from the analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 
will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy. 
*Value obtained during infection and considered to be confounded. 
SOURCE: Listing 16.2.6.2.4 
Programming Note: If a patient has multiple values at a particular time point, use mean.  


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Figure 14.4.1.4b 
Monocytes over Time by Dose Level 
Safety Population 
 
Header: Treatment Level (mg) = XXX 
Y-axis: AMC Value (10^9/L) 
X-axis: Hours Since Study Treatment 
Footnote:  
Note: The imputation of BOCF is used for missing 24 hour assessment. Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not 
getting dense PK samples for the first few hours. Therefore, samples were taken the next day and the timepoints that were missed the day before were replaced with these samples. 
Patient 
, assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was 
used as time 0. Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were 
excluded from the analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 
will be excluded from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy. 
SOURCE: Listing 16.2.6.2.4 
 
Programming Note: If a patient has multiple values at a particular time point, use mean. 
 
  
 


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Figure 14.4.1.5 
Mean (+/– SE) Plasma Concentration - Time Profile of X4P-001 by Dose Level 
Safety Population 
 
 
 
Header: Treatment Level (mg) = XXX 
Y-axis: Mean X4P-001 plasma concentrations (ng/mL) 
X-axis: Time Point (hours postdose) 
SOURCE: Table 14.4.1 
 
Programming Note:All visits will be presented on the same figure. If a patient has multiple values at a particular time point, use median. 
 
 
Dose ~e .. r e l 
5 ® rng 
i 
iU!IO OO 
-=-
11 ®® rng 
···D··· 115 ® rng 
2 1Jll1Jll rng 
0 
'+:I 
----
3 ®® rng 
1000 
.......... 4 1Jll1Jll rng 
... 
0 ... 
1 0 0 
00 
<'II 
i5. 
1 0 
... .e 
<'II 
>< 
·;:: 
0 
-
0 
0 
4 
s 
112 
2 4 
1 in11 e aifle ir d,o se ( Imo l!J irs} 


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Figure 14.4.1.6 
Mean Dose Response of ANC - Time Profile 
Safety Population  
 
 
 
 
 
Y-axis: Mean Neutrophils (10^9/L) 
X-axis: Time Point (hours postdose) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
The ANC threshold (500 neutrophils per microliter) is indicated by the blue line. 
SOURCE: Listing 16.2.8.2 
 
Programming Note: All visits will be presented on the same figure. If a patient has multiple values at a particular time point, use mean. No reference line required. All relevant visits 
should be used for derivation, and not limited to Weeks 5, 13 and 21. 
 
 
j 
ti) 
Q) u 
1.0 
0 0.5 
-
u z 
<t 
C 
IQ 
Q) 
:ii: 
• 
• 
8 -----
0 -1-----------.----.----.---, 
0 
4 
8 
12 
16 
20 
24 
Time after dose (hours) 


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Figure 14.4.1.7 
Mean Dose Response of ALC - Time Profile 
Safety Population 
 
(Same shell as Table 14.4.1.6) 
 
Y-axis: Mean Lymphocytes (10^9/L) 
X-axis: Time Point (hours postdose) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
The ALC threshold (1000 cells per microliter) is indicated by the blue line. 
SOURCE: Listing 16.2.8.2 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use mean. Reference line at y=1 required. All relevant 
visits should be used for derivation, and not limited to Weeks 5, 13 and 21 
 
 
 
 
Figure 14.4.1.8 
Mean Dose Response of Monocytes - Time Profile 
Safety Population 
 
(Same shell as Table 14.4.1.6) 
 
 
Y-axis: Mean Monocytes (10^9/L) 
X-axis: Time Point (hours postdose) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Listing 16.2.8.2 
 
Programming Note: All visits will be presented on the same figure. If a patient has multiple values at a particular time point, use mean. No reference line required. All relevant visits 
should be used for derivation, and not limited to Weeks 5, 13 and 21 
 
 
 
 


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Figure 14.4.1.9 
Box plots of WBC change from baseline ratio at 300mg and 400mg by Dose Level 
Safety Population 
 
 
 
 
Y-axis: WBC Change from baseline (ratio) 
X-axis: X4P-001 dose (mg QD) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Listing 16.2.8.2 
 
Programming Note: All visits will be presented on the same figure. Use mean value across visits. 
The ratio is to be calculated as visit value / baseline value, same as fold-change. 
 
-
0 
'.;.. !. 
(ll 
C 
11 
1i 
(It 
J 
E: e 
.... 
II) 
C'l 
C: 
l1' 
.c 
(..) 
u 
co 
1 
I 
I 
-- --
I 
mg 
N=6 
Mavorixafor dose (mg QD) 
mg 
N=3 


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Figure 14.4.1.10 
Box plots of AUC for ANC by Dose Level 
Safety Population 
 
 
 
 
 
Y-axis: AUCANC (10^9/L) 
X-axis: X4P-001 dose (mg QD) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Table 14.2.6.2.1 
 
Programming Note: All visits will be presented on the same figure. If a patient has multiple values at a particular time point, use mean. 
 
 
--··, 
20000 
...J 10000 
:::,. I 
0 
" 
u -10000 
::, 
<X 
_[ o D 
-20000~------------------
50 mg 100 mg 150 mg 200 mg 300 mg 400 mg 
N=2 
N=4 
N=2 
N=3 
N=6 
N=3 
Mavorixafor dose (mg QD) 
Dose level 
50 mg 
100 mg 
D 
150 mg 
200 mg 
D 
300 mg 
D 
400 mg 


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Figure 14.4.1.11 
Scatter Plot of Time above Threshold values for ANC versus AUC for ANC 
Safety Population 
 
 
 
Y-axis: Time Above Threshold for ANC (hours) 
X-axis: X4P-001 AUC (ng*hr/mL) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
 
SOURCE: Table 14.2.9, Listing 16.2.6.2.3 
 
Programming Note: display Pearson correlation coefficient (r) in the plot 
 
 
Figure 14.4.1.12 
Scatter Plot of Time above Threshold values for ALC versus AUC for ALC 
Safety Population 
 
(Same shell as Table 14.4.1.11) 
 
Y-axis: Time Above Threshold for ALC (hours) 
X-axis: X4P-001 AUC (ng*hr/mL) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Table 14.2.10, Listing 16.2.6.2.3 
 
Programming Note: display Pearson correlation coefficient (r) in the plot 
 
i(I 
.. 
5000 
r= 0.54 
20000 
IMav,orixa.for Al.JC na1•filo11r/mlL) 


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Figure 14.4.1.13.1 
Plot of Yearly Infection Rate by Dose Level 
Safety Population  
 
 
 
Y-axis: Annualized Infection Rate (95% CI) 
X-axis: X4P-001 dose (mg QD) 
SOURCE: Table 14.3.2.7.1 
 
Programming Note: For Rate use ADIR.PARAMCD=OINFRATE. For number of infection events use NOINF along with appropriate DOSEA.  
Table 14.3.2.7 doesn’t have a pre-study column.  
 
Add footnote:  
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”.  Rate is defined as number of infection events in a given dose level /duration of exposure 
on a dose level in years. 95% CI is based on normal approximation. Events at dose level are assigned based on the start date of the event occurring within start and end dates of that 
dose for each patient. Confidence limits below 0 are not shown. 
mo~-~-~----~-~----~-~----~-~--
:1 
la: 
C < 
Pre-s1udy 
N=.8 
50-151) mg 
Nl=4 
300mg 
IN=7 
Mavmixafo:r dose ,(mg QDI 
400mg 
N=3 


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Figure 14.4.1.13.2 
Plot of Yearly Infection Score by Dose Level 
Safety Population 
 
Y-axis: Infection Score (95% CI) 
X-axis: X4P-001 dose (mg QD) 
SOURCE: Table 14.2.2.3 
 
Programming Note: For Rate use ADIR.PARAMCD=OINFSC along with appropriate DOSEA. Pre-study infection score is not calculated. 
Table 14.3.2.7 doesn’t have a pre-study column. 
Add footnote:  
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”. Infection Score is defined as number of infection events in a given dose level divided by 
duration of exposure on a dose level, in years. 95% CI is based on normal approximation. Events at dose level are assigned based on the start date of the event occurring within start 
and end dates of that dose for each patient. 
 


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Figure 14.4.1.14.1 
Plot of Yearly Infection Rate for Subjects on 300mg and 400 mg Dose Levels by 6 Month Intervals 
Safety Population  
 
 
 
Y-axis: Annualized Infection Rate (95% CI) 
X-axis: Time on Study 
SOURCE: Table 14.3.2.6.1 
Programming Note:  
For Pre-study infection rate use ADIR.PARAMCD=PINFRATE 
For 0-6 months, ADIR.PARAMCD=OINFRTBP and DOSEA in (300,400) and ETINFG1=0 – 6 Months.  
For 6-12 months, ADIR.PARAMCD=OINFRTBP and DOSEA in (300,400) and ETINFG1=6 – 12 Months.  
And so on… 
For 0-6 months, for Number of infection events- ADIR.NOINFBP and DOSEA in (300,400) and ETINFG1=0 – 6 Months. 
 
For 6-12 months, for Number of infection events- ADIR.NOINFBP and DOSEA in (300,400) and ETINFG1=6 – 12 Months. 
And so on… 
 
Add footnote: 
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”. The reporting period starts on the 300 mg dose date. Rate is defined as number of 
infection events in a given period /duration of period in years. 95% CI is based on normal approximation. Only events with start date occurring within start and end dates of 300/400 mg 
dose for each patient are included. Time period assignment is based on the start date of the event. Confidence limits below 0 are not shown. 
 
 
Pre-study 
IN=7 
0-6 1mon1!lils, 
N=7 
6-12 monttls 
N=5 
Time· on stu dly 
>12 1mo1111!lils, 
N=5 


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Figure 14.4.1.14.2 
Plot of Yearly Infection Score for Subjects on 300 mg and 400 mg Dose Levels by 6 Month Intervals 
Safety Population  
Y-axis: Infection Score (95% CI) 
X-axis: Time on Study 
SOURCE: Table 14.3.2.6.2 
Programming Note:  
For Pre-study infection rate use ADIR.PARAMCD=NPINF and DOSEA in (300,400). 
For 0-6 months, ADIR.PARAMCD=OINFSCBP and DOSEA in (300,400) and ETINFG1=0-6 Months.  
For 6-12 months, ADIR.PARAMCD=OINFSCBP and DOSEA in (300,400) and ETINFG1=6-12 Months. 
… 
For 0-6 months, for Number of infection events- ADIR.OINFSCBP and DOSEA in (300,400) and ETINFG1=0-6 Months. 
For 6-12 months, for Number of infection events- ADIR.OINFSCBP and DOSEA in (300,400) and ETINFG1=6-12 Months.  
… 
Pre-study infection score is not calculated. 
 
Add footnote: 
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”. The reporting period starts on the 300 mg dose date. Rate is defined as number of 
infection events in a given period /duration of period in years. 95% CI is based on normal approximation. Only events with start date occurring within start and end dates of 300/400 mg 
dose for each patient are included. Time period assignment is based on the start date of the event. 
 
 


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Figure 14.4.2.1 
Scatter Plot of Plasma Drug Level and ANC 
Safety Population 
 
 
Y-axis: Neutrophils (10^9/L) 
X-axis: X4P-001 plasma concentration (ng/mL) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Table 14.4.1, Listing 16.2.6.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use mean. 
 
Figure 14.4.2.2 
Scatter Plot of Plasma Drug Level and ALC 
Safety Population 
 
 
Y-axis: Lymphocytes (10^9/L) 
X-axis: X4P-001 plasma concentration (ng/mL) 
Patient 
, Extension Phase - Residence Visit 1 Post EOS and Extension Phase – Residence Visit 3 occurred during episodes of infection. These values were excluded from the 
analysis. Patient 
, Week 21 occurred during an episode of infection. These values were excluded from the analysis. Dense sample data for subject 
 will be excluded 
from the TAT summary tables and figures since the WBC, ANC, ALC, and AMC levels were normal at screening due to splenectomy.  
SOURCE: Table 14.4.1, Listing 16.2.6.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use mean. 
 
Figure 14.4.3.1 
Mean Plasma Concentrations of X4P-001 vs Nominal Time (Dense Sampling Visits) by Dose Level - Linear Scale 
Safety Population 
 
Header: Treatment Level (mg) = XXX 
Y-axis: Mean X4P-001 plasma concentration (ng/mL) 
X-axis: Time Point (hours postdose) 
SOURCE: Table 14.4.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use median. 
 
Figure 14.4.3.2 
Mean Plasma Concentrations of X4P-001 vs Nominal Time (Dense Sampling Visits) by Dose Level - Semi-Logarithmic Scale 
Safety Population 
 
Header: Treatment Level (mg) = XXX 
Y-axis: Mean X4P-001 plasma concentration (ng/mL) 
X-axis: Time Point (hours postdose) 
SOURCE: Table 14.4.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use median. 


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Figure 14.4.4.1 
Subject Plasma Concentrations of X4P-001 vs Nominal Time (Dense Sampling Visits) by Dose Level - Linear Scale 
Safety Population 
 
Header: Patient ID = XXX, Treatment Level (mg) = XXX 
Y-axis: X4P-001 plasma concentration (ng/mL) 
X-axis: Time Point (hours postdose) 
SOURCE: Listing 16.2.5.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use median. 
 
 
Figure 14.4.4.2 
Subject Plasma Concentrations of X4P-001 vs Nominal Time (Dense Sampling Visits) by Dose Level - Semi-Logarithmic Scale 
Safety Population 
 
Header: Patient ID = XXX, Treatment Level (mg) = XXX 
Y-axis: X4P-001 plasma concentration (ng/mL) 
X-axis: Time Point (hours postdose) 
SOURCE: Listing 16.2.5.1 
 
Programming Note: All visits will be presented on the same figure, If a patient has multiple values at a particular time point, use median. 
 
 
 


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14.4. 
Planned Listing Shells 
Global programming note: for all listings, sort by subject number. Further sorting instructions will be provided if needed. 
 
 


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Listing 16.2.1 
Subject Disposition 
All Enrolled Patients 
Subject 
Number 
Gender 
Date of Last Dose 
(Day) [1] 
Phase II Treatment Period 
 
Extension 
Phase 
 
End of Study 
Status 
Date of Completion/ 
Discontinuation 
(Day) [1] 
Reason for Discontinuation 
 
Status 
 
Date Extension Phase 
Discontinued 
Reason for 
Discontinuatio
n 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
Male 
DDMMMYYYY (X) 
Off 
DDMMMYYYY (XX) 
 
 
Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
Female 
DDMMMYYYY (X) 
Off 
DDMMMYYYY (XX) 
 
 
N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
 
DDMMMYYYY (X) 
Off 
DDMMMYYYY (XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
 
DDMMMYYYY (X) 
Off 
DDMMMYYYY (X) 
XXXXXXXXXX: XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
 
DDMMMYYYY (X) 
Off 
DDMMMYYYY (XX) 
XXXXXXXXXXXXXXXXXXXX
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. If patient is still taking study drug, then data extraction date is used. 
A subject that is no longer in the Phase II Treatment Period has a status of ‘Off’. 
 
Programming Note: If reason for early termination is other, concatenate the specify text as follows: “Other: XXXXXXXXX”. 
If reason for early termination is lost to follow-up, concatenate with date of last contact as follows: “Lost to follow-up; date of last contact: DDMMMYYYY”. 
If reason for discontinuation is a PI decision, concatenate PI decision reason as follows: “PI Decision: XXXXXXXXXXX”. 
 
 


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Listing 16.2.2.1 
Eligibility Criteria Not Met 
All Enrolled Patients 
 
 
Date 
 
 
Subject Number 
Gender 
Screening (Day)[1] 
Informed Consent (Day)[1] 
All Inclusion 
Criteria Met? 
Any Exclusion 
Criteria Met? 
 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
Yes 
No 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
No: 02, 09 
No 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
No: 06 
No 
 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
Yes 
Yes: 06 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
Yes 
No 
 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (-X) 
DDMMMYYYY (-X) 
Yes 
No 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
Programming note: If more than 1 inclusion or exclusion criterion number exists, concatenate with a comma. Decode any relevant criteria in the footnotes. 
 
 


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Page 124 of 172 
Listing 16.2.2.2 
Protocol Deviations 
Safety Population 
 
 
Subject 
Number 
Gender 
Deviation Date Deviation Category 
Violation 
Level 
Description 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY 
XXXXXXXXXXX 
Important (NCS) 
XXXXXXX 
 
XXXXXXXXXXXXXX 
Non-Important 
XXXXXXXXXXXXXXX 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY 
XXXXXXXXXXXX 
Non-Important 
XXXXXXXXXXXXXXXXXXX 
 
XXXXXXXXXXXXXXXX 
Non-Important 
XXXXXXXXXXX 
 
 
 
 
XXXXXX 
XXXXXX 
DDMMMYYYY 
XXXXXXXXXXXX 
Important (CS) 
XXXXXXXXXXXXXXXXXXXX 
 
 
 
 
Abbreviations: CS = Clinically significant; NCS = Not clinically significant. 
 
 


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Page 125 of 172 
Listing 16.2.3 
Analysis Populations 
All Enrolled Patients 
 
Subject Number 
Gender 
SP 
[1] 
ITT 
[2] 
 
 
 
 
XXXXXX 
XXXXXX 
Yes 
No 
 
 
 
 
XXXXXX 
XXXXXX 
Yes 
Yes 
 
 
 
 
XXXXXX 
XXXXXX 
No 
No 
 
 
 
 
Abbreviations: ITT = Intent to Treat Population; SP= Safety Population. 
[1] The Safety Population includes all patients who receive any amount of study medication. 
[2] The ITT Population is the same as the Safety Population and includes all patients who receive any amount of study medication. 
 
 


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Page 126 of 172 
Listing 16.2.4.1 
Demographics and Baseline Characteristics 
Safety Population 
 
 
 
Age 
 
 
Weight 
Height 
BMI 
Subject Number 
Gender 
(years) 
Ethnicity 
Race 
(kg) 
(cm) 
(kg/m2) 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
XX 
Not Hispanic or 
Latino 
XXXXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
XX 
Hispanic or Latino 
XXXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
XX 
 
XXXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XX 
 
XXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
XXXXXX 
XXXXXX 
XX 
 
XXXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
XXXXXX 
XXX 
XX 
 
XXXXXX 
XX.X 
XX.X 
XX.XX 
 
 
 
 
 
 
 
 
Abbreviation: BMI = Body mass index  
         
 
 
 
Programming Note: If race is other, concatenate “Other:” with specify text. If patient has multiple races, concatenate them  
 


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Page 127 of 172 
Listing 16.2.4.2 
Medical History 
Safety Population 
 
Subject 
Number 
System Organ Class / 
  Preferred Term / 
    Verbatim Term 
Start date(Day) / 
  End Date(Day)[1] 
Currently Active? 
XXXX/ 
  XXX/ 
    XXX  
DDMMMYYYY(XX) /  
  DDMMMYYYY(XX) 
 
 
 
 
XXXX/ 
  XXX/ 
    XXX 
DDMMMYYYY(XX) / 
  DDMMMYYYY(XX) 
 
 
 
 
XXXX/ 
  XXX/ 
    XXX 
DDMMMYYYY(XX) / 
  DDMMMYYYY(XX) 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) if prior to the administration of first study drug. 
 
 


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Page 128 of 172 
Listing 16.2.4.3.1 
History of WHIM Syndrome - Hospitalizations 
Safety Population 
Subject Number 
Prior Hospitalization for 
Infection? 
Start Date (Day) /  
End Date (Day) [1] 
Reason for Hospitalization 
Duration [2] 
Yes 
DDMMMYYYY (XX) / 
DDMMMYYYY (XX) 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) if prior to the administration of first study drug. 
[2] Duration = End Date – Start Date + 1 
 
  
 


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Page 129 of 172 
Listing 16.2.4.3.2 
History of WHIM Syndrome - Infections Managed as Out-Patient 
Safety Population 
 
Subject 
Number 
Any Prior Infections Managed 
as Out-Patient? 
Start Date (Day)/ 
End Date (Day) [1] 
Antibiotic Used? 
Type of Infection 
Duration [2] 
Yes 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
Yes 
 
 
 
 
 
 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] Duration = End Date – Start Date + 1 
 
 
 
 
  
 


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Page 130 of 172 
Listing 16.2.4.3.3 
History of WHIM Syndrome - Prior Treatments for WHIM syndrome 
Safety Population 
 
Subject Number 
Any Prior 
Treatments of 
WHIM? 
Agent 
Start Date (Day)/ 
End Date (Day) [1] 
 
Route 
AE Related to 
Treatment 
Best 
Clinical 
Response 
(Specify) 
Reason for discontinuation 
(Specify) 
 
 
DDMMMYYYY(XX)/ 
DDMMMYYYY(XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) if prior to the administration of first study drug. 
 
  
 


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Page 131 of 172 
Listing 16.2.4.3.4 
WHIM Syndrome Genotyping 
Safety Population 
 
Subject Number 
Was Genotyping 
Sample Collected? 
Date Collected (Day) [1] 
CXCR4 Genotyping Variant 
WHIM Diagnosis  
Date 
Yes 
DDMMMYYYY(XX) 
Other: XXXXXX 
DDMMMYYYY 
 
 
 
 
 
DDMMMYYYY (XX) 
 
 
 
 
 
 
 
DDMMMYYYY (XX) 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
 
 


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Page 132 of 172 
Listing 16.2.4.4.1 
Study Drug Administration 
Safety Population 
 
Subject 
Number 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Did Subject 
Receive 
Treatment? 
Start Date (Day)/ 
Stop Date (Day) [1] 
Number of 
Days on Dose 
Level [2] 
Ongoing? 
Route 
Frequency 
Any Doses 
Not 
Taken? 
Reason 
Not 
Taken 
Number Of Doses 
Not Taken  
25  
100  
Yes 
DDMMMYYYY (XX)/ 
DDMMMYYYY (XX) 
 
Yes 
Oral 
QD 
 
 
 
25  
100  
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
100  
100  
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
400  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] Number of days on Dose Level = Last Date on Dose Level - Start Date on Dose Level + 1. 
  
 


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Page 133 of 172 
Listing 16.2.4.4.2 
Study Drug Exposure 
Safety Population 
 
Subject 
Number 
Capsule 
Strength 
(mg) 
Dose Level 
(mg) 
Total number 
of Capsules 
Dispensed 
Date Dispensed (Day) 
[1] 
Total number of 
Capsules 
Returned 
Date Returned (Day) 
[1] 
Percent 
compliance 
Treatment 
Duration 
Number of 
Doses 
Missed or 
skipped 
25  
100  
 
DDMMMYYYY (XX) 
 
DDMMMYYYY (XX) 
 
 
 
25  
100  
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
100  
100  
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percent compliance = [1-(Total number of capsules returned/Total number of capsules dispensed)] x 100.  
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
 
 


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Page 134 of 172 
Listing 16.2.4.5 
Assessment of Warts 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Was 
Assessment 
of Warts Done? 
Date Performed 
(Day) [1] 
Area of 
Assessment 
Were any warts in  
area of assessment? 
Number of 
warts in the 
area of 
assessment 
Change from 
baseline in 
the number of 
warts 
 
 
Screening 
 
 
Yes 
DDMMMYYYY (X) 
BOTTOM LEFT FOOT 
No 
 
 
 
 
 
 
 
 
BOTTOM LEFT HAND 
No 
 
 
 
 
 
 
 
 
BOTTOM RIGHT FOOT 
Yes 
2 
 
 
 
 
 
 
 
BOTTOM RIGHT HAND 
No 
 
 
 
 
 
 
 
 
TOP LEFT FOOT 
No 
 
 
 
 
 
 
 
 
TOP LEFT HAND 
No 
 
 
 
 
 
 
 
 
TOP RIGHT FOOT 
No 
 
 
 
 
 
 
 
 
TOP RIGHT HAND 
No 
 
 
 
 
 
 
 
 
TOTAL NUMBER OF WARTS ACROSS 
ALL AREAS OF ASSESSMENT 
<<If any of above=Yes 
then populate cell to 
the right>> 
XX 
 
 
Day 1 
25 
50 
Yes 
DDMMMYYYY (X) 
BOTTOM LEFT FOOT 
No 
 
 
 
 
 
 
 
 
BOTTOM LEFT HAND 
No 
 
 
 
 
 
 
 
 
BOTTOM RIGHT FOOT 
Yes 
XX 
 
 
 
 
 
 
 
BOTTOM RIGHT HAND 
No 
 
 
 
 
 
 
 
 
TOP LEFT FOOT 
No 
 
 
 
 
 
 
 
 
TOP LEFT HAND 
No 
 
 
 
 
 
 
 
 
TOP RIGHT FOOT 
No 
 
 
 
 
 
 
 
 
TOP RIGHT HAND 
No 
 
 
 
 
 
 
 
 
TOTAL NUMBER OF WARTS ACROSS 
ALL AREAS OF ASSESSMENT 
<<If any of above=Yes 
then populate cell to 
the right>> 
XX 
 
 
Week 5 
25 
50 
Yes 
DDMMMYYYY (X) 
BOTTOM LEFT FOOT 
No 
 
 
 
 
 
 
 
 
BOTTOM LEFT HAND 
No 
 
 
 
 
 
 
 
 
BOTTOM RIGHT FOOT 
Yes 
XX 
XX 
 
 
 
 
 
 
… 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
Note: Baseline is the number of warts at Day 1. 
An out of schedule assessment of warts was done at end of study visit for subject 
. 
Patient 
was re-enrolled into the study on DDMMMYYYY. 
Patient 
was re-enrolled into the study on DDMMMYYYY. 
 
 
Programming Note: present all data including data after re-enrollment for the 2 re-enrolled patients  
 


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Page 135 of 172 
Listing 16.2.4.6 
Revaccination 
Safety Population 
 
Subject 
Number 
Date of Dose 
(Day) [1] 
Capsule 
strength 
(mg) 
Dose  
Level  
(mg) 
Was Patient Revaccinated?     
Type Of Revaccination 
Date Of Revaccination (Day) [1] 
DDMMMYYYY (XX) 
25 
100  
Yes 
Tetanus toxoid 
DDMMMYYYY (XX) 
DDMMMYYYY (XX) 
 
100  
 
 
 
DDMMMYYYY (XX) 
 
200  
 
 
 
DDMMMYYYY (XX) 
 
300  
 
 
 
 
 
 
 
 
 
DDMMMYYYY (XX) 
 
100  
 
 
 
DDMMMYYYY (XX) 
 
100  
 
 
 
DDMMMYYYY (XX) 
 
100  
 
 
 
DDMMMYYYY (XX) 
 
200  
 
 
 
 
 
 
 
 
 
DDMMMYYYY (XX) 
 
200  
 
 
 
 
DDMMMYYYY (XX) 
 
200  
 
 
 
 
DDMMMYYYY (XX) 
 
300  
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
  
 


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Page 136 of 172 
Listing 16.2.4.7 
Bone Marrow Aspirate 
Safety Population 
 
Subject Number 
Visit 
Date Performed (Day) [1] 
Was Bone Marrow aspirate Performed?     
Screening 
 
Yes 
Week 25 
 
 
 
 
 
Day 1 
 
 
Week 5 
 
 
Week 13 
 
 
Week 21 
 
 
 
 
 
Day 1 
 
 
 
Week 5 
 
 
 
Week 13 
 
 
 
Week 21 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
  
 


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Page 137 of 172 
Listing 16.2.5.1 
Pharmacokinetic Blood Collection and Concentrations 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
strength  
(mg) 
Dose  
Level  
(mg) 
Was the Sample 
collected? 
 
Reason Sample Not 
Collected 
Date/Time 
Collected (Day) [1] 
Time Point 
X4P-001 
Concentration 
(ng/mL) 
 
Day 1 
25  
100  
Yes 
xxxxx 
DDMMMYYYY (X) 
Predose 
xxxx 
 
 
 
 
 
 
 
30 mins postdose 
xxxx 
 
 
 
 
 
 
 
60 mins postdose 
xxxx 
 
 
 
 
 
 
 
90 mins postdose 
xxxx 
 
 
 
 
 
 
 
2 hours postdose 
xxxx 
 
 
 
 
 
 
 
3 hours postdose 
xxxx 
 
 
 
 
 
 
 
4 hours postdose 
xxxx 
 
 
 
 
 
 
 
8 hours postdose 
xxxx 
 
 
 
 
 
 
 
12 hours postdose 
xxxx 
 
 
 
 
 
 
 
16 hours postdose 
xxxx 
 
 
 
 
 
 
 
24 hours postdose 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not getting dense PK samples for the first few hours. Therefore, samples were 
taken the next day and the timepoints that were missed the day before were replaced with these samples. Patient 
, assessments on 21 and 22 February 2018 were analyzed 
and presented as Week 21 assessments.  
 
 


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Page 138 of 172 
Listing 16.2.5.2 
Calculated Pharmacokinetic Parameters 
Safety Population 
 
Subject 
Number 
Visit 
Actual dose 
of X4P-001 (mg) 
AUC Over Dosing 
Interval (h*ng/mL) 
Tmax 
(h) 
Cmax 
(ng/mL) 
Week 5 
100  
Yes 
 
Yes 
Week 13 
100  
 
 
 
Week 21 
200  
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 5 
100  
 
 
 
Week 13 
200  
 
 
 
Week 21 
100  
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 5 
200  
 
 
 
 
Week 13 
200  
 
 
 
 
Week 21 
300  
 
 
 
 
 
 
 
 
 
Note: Imputed concentrations at 24 hours with predose values were used for PK parameter calculation. 
Abbreviation: AUC = Area under the plasma concentration; Cmax = Maximum plasma concetration; Tmax = Time to Cmax.  
 
Programming note: please use AUCtau to report match with tables 
 


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Page 139 of 172 
 
 
 
Listing 16.2.6.1 
ANC/ALC Sample Collection 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Test 
Threshold Adjusted 
AUC (cell.hr/uL) [1] 
Time Point 
Collection Date/Time 
Hours from Previous 
Sample 
Result 
(cell/uL) [2] 
Comments 
 
Week 5 
25  
100  
ALC 
 
Time 0 
DDMMMYYYY/ HH:MM  
X.XXXX 
 XX 
 
 
 
 
 
 
 
30 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
60 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
90 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
2 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
3 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
4 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
8 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
12 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
16 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
24 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
(BOCF) 
 
 
Week 
13 
25  
100  
ALC 
 
Time 0 
DDMMMYYYY/ HH:MM  
X.XXXX 
 XX 
 
 
 
 
 
 
 
30 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
60 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
90 Minutes 
DDMMMYYYY/ HH:MM  
X.XXXX 
XX 
 
 
 
 
 
 
 
2 Hours 
DDMMMYYYY/ HH:MM  
X.XXXX 
XXX 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AUC = Threshold adjusted area under the plasma concentration curve, BOCF = baseline observation carried forward. 
[1] Threshold adjusted AUC is calculated using the trapezoidal method with area above threshold being positive, and area below threshold negative. The threshold is defined as 600/uL 
for ANC and as 1000/uL for ALC. 
[2] The imputation of BOCF is used for missing 24 hour assessment. Imputation is not used for intermediate missing assessments. Repeat assessments are not used in AUC calculation.  
Patients 
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not getting dense PK samples for the first few hours. Therefore, samples were 
taken the next day and the timepoints that were missed the day before were replaced with these samples. Patient 
, assessments on 21 and 22 February 2018 were analyzed 
and presented as Week 21 assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was used as time 0. 


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Page 140 of 172 
Listing 16.2.6.2.1 
Threshold Adjusted AUC values for ANC 
Safety Population 
 
Subject Number 
Visit 
Capsule 
Strength (mg) 
Dose 
Level (mg) 
Threshold Adjusted AUC (cell.hr/uL) [1] 
Week 5 
25 
50 
XXXX.XXXX 
Week 13 
25 
100 
 
Week 21 
25 
200 
 
 
 
 
 
 
 
 
 
Week 5 
100 
 
 
Week 13 
100 
 
 
Week 21 
100 
 
 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
Week 13 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
 
Abbreviation: AUC = Threshold adjusted area under the plasma concentration curve. 
*Value obtained during infection and considered to be confounded, value has not been used in the analysis. 
**Patient had normal value at Screening, therefore values have not been used in the analysis. 
[1] Threshold adjusted AUC is calculated using the trapezoidal method with area above threshold being positive, and area below threshold negative. The threshold is defined as 
600/uL for ANC. 
 


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Page 141 of 172 
 
Listing 16.2.6.2.2 
Threshold Adjusted AUC values for ALC 
Safety Population 
 
(Same shell as Listing 16.2.6.2.1) 
 
 
 
Footnote:  
Abbreviation: AUC = Threshold adjusted area under the plasma concentration curve. 
*Value obtained during infection and considered to be confounded, value has not been used in the analysis. 
**Value was normal at Screening, therefore values have not been used in the analysis. 
[1] Threshold adjusted AUC is calculated using the trapezoidal method with area above threshold being positive, and area below threshold negative. The threshold is defined as 1000/uL 
for ALC. 
 


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Page 142 of 172 
Listing 16.2.6.2.3 
Time Above Threshold by Dose Level - Assessment of ANC/ALC/AMC  
Safety Population 
 
Subject Number 
Test 
Dose Level (mg) 
Time above Threshold (Hours) [1] 
 
 
ALC 
50 
XX.XX 
 
 
100 
XX.XX 
 
 
150 
XX.XX 
 
 
300 
XX.XX 
 
 
400 
XX.XX 
 
 
50/100/150 
XX.XX 
 
 
300/400 
XX.XX 
 
 
AMC 
50 
XX.XX 
 
 
100 
XX.XX 
 
 
150 
XX.XX 
 
 
300 
XX.XX 
 
 
400 
XX.XX 
 
 
50/100/150 
XX.XX 
 
 
300/400 
XX.XX 
 
 
ANC 
50 
XX.XX 
 
 
100 
XX.XX 
 
 
150 
XX.XX 
 
 
300 
XX.XX 
 
 
400 
XX.XX 
 
 
50/100/150 
XX.XX 
 
 
300/400 
XX.XX 
 
 
ALC 
50 
XX.XX 
 
 
100 
XX.XX 
 
 
150 
XX.XX 
 
 
300 
XX.XX 
 
 
400 
XX.XX 
 
 
50/100/150 
XX.XX 
 
 
300/400 
XX.XX 
 
… 
 
 


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Page 143 of 172 
Subject Number 
Test 
Dose Level (mg) 
Time above Threshold (Hours) [1] 
 
Note: If time above threshold was >24 hours, it was rounded off to 24.  
*Value obtained during infection and considered to be confounded, value has not been used in the analysis. 
**Value was normal at Screening, therefore values have not been used in the analysis. 
[1] The threshold is defined as 500/uL for ANC, as 1000/uL for ALC, as 190/uL for females aged 12 to 18, 180/uL for males aged 12 to 18, 250/uL for females aged >=18 and 290/Ul 
for males aged >=18 for AMC. 
 
 
 
 
 
 
 
 
 
 


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Page 144 of 172 
Listing 16.2.6.2.4 
Time Above Threshold - Assessment of ANC/ALC/AMC with Time Crossed 
Safety Population 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Test 
Time Point 
Collection Date/Time 
Result 
(cell/uL) 
Comments 
Time 
Crossed 
Time 
above 
Threshold 
(Hours) 
[1] 
 
 
Week 5 
25 
50 
ALC 
Time 0 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
0 
 
 
 
 
 
30 Minutes 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
60 Minutes 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
90 Minutes 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
2 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
3 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
4 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
8 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
12 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
16 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
XX.XX 
 
 
 
 
 
24 Hours 
DDMMMYYYY/ HH:MM 
XXXX 
SNS: SAMPLE NOT SUBMITTED 
. 
XX.XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AMC 
Time 0 
DDMMMYYYY/ HH:MM 
XXXX 
 
HH:MM 
0 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
ANC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: BOCF = baseline observation carried forward. 
Note: The imputation of BOCF is used for missing 24 hour assessment. Imputation is not used for intermediate missing assessments. Repeat assessments are not used in AUC calculation. Patients 
      
 and 
 took the Week 5 dose at home instead of the clinic resulting in the site not getting dense PK samples for the first few hours. Therefore, samples were taken the next day 
      and the timepoints that were missed the day before were replaced with these samples. The time above threshold values are calculated based on the separate days. Patient 
 assessments on 21 and 22 February 2018 were analyzed and presented as Week 21 
      assessments. For patient 
 the assessment on 20FEB2018 at 9:25 was used as time 0. Time crossed contains the time at which the AUC value crossed the threshold in either direction. 
*Value obtained during infection and considered to be confounded, value has not been used in the analysis  
[1] The threshold is defined as 500/uL for ANC, as 1000/uL for ALC, as 190/uL for females aged 12 to 18, 180/uL for males aged 12 to 18, 250/uL for females aged >=18 and 290/uL for males aged 
>=18 for AMC. 
 
 


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Page 145 of 172 
Listing 16.2.7.1 
Treatment Emergent Adverse Events 
Safety Population 
 
Subject 
Number 
Capsule 
strength  
(mg) 
Dose 
Level  
(mg) 
System Organ Class/ 
 Preferred Term/ 
  Verbatim Term 
Start Date (Day) / 
  End Date (Day) [1]  
Severity [2]/ 
Relationship 
Outcome/ 
Action Taken   
Other 
Action 
Taken 
Serious?  
 
25 
100  
XXXXXXXXXXXXX/ 
 XXXXXXXXXX/ 
  XXXXXXXXXXXX 
DDMMMYYYY (X)/ 
  DDMMMYYYY (X) 
Grade X/ 
Unrelated 
RECOVERED/RESOLVED/  
DOSE NOT CHANGED 
 
No 
 
 
 
 
 
 
 
 
 
 
25 
100  
XXXXXXXXXXXXX/ 
 XXXXXXXXXX/ 
  XXXXXXXXXXXX 
DDMMMYYYY (X)/ 
  DDMMMYYYY (X) 
Grade X/ 
Unrelated 
RECOVERED/RESOLVED/  
DOSE NOT CHANGED 
 
No 
 
 
 
 
 
 
 
 
 
 
100 
200  
XXXXXXXXXXXXX/ 
 XXXXXXXXXX/ 
  XXXXXXXXXXXX 
DDMMMYYYY (X)/ 
  DDMMMYYYY (X) 
Grade X/ 
Unrelated 
RECOVERED/RESOLVED/  
DOSE NOT CHANGED 
 
No 
 
 
 
 
 
 
 
 
 
 
100 
300  
XXXXXXXXXXXXX/ 
 XXXXXXXXXX/ 
  XXXXXXXXXXXX 
DDMMMYYYY (X)/ 
  DDMMMYYYY (X) 
Grade X/ 
Unrelated 
RECOVERED/RESOLVED/  
DOSE NOT CHANGED 
 
No 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
 
Programming Note: Sort Adverse Events by Patient, Start Date, System Organ Class and Preferred Term 
 
 


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Page 146 of 172 
Listing 16.2.7.2 
Adverse Events that occur during Screening and ended before Exposure to study Drug 
Safety Population 
 
Subject 
Number 
System Organ Class/ 
 Preferred Term/ 
  Verbatim Term 
Start date(Day) / 
End Date(Day) [1] 
 
Severity[2] 
    
Outcome/ 
Action Taken   
Other Action Taken 
Serious?/ 
Reason for SAE    
 
DDMMMYYYY(XX)/ 
DDMMMYYYY(XX) 
Grade 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: SAE = Serious adverse event. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] The severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
 
Programming Note: Sort Adverse Events by Patient, Start Date, System Organ Class and Preferred Term 
 
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
Confidential 
 
 
 
 
 
Page 147 of 172 
Listing 16.2.7.3 
Infections Reported as Adverse Events 
Safety Population 
 
Subject 
Number 
Capsule 
Strength 
(mg) 
Dose Level 
(mg) 
AE # 
Infection 
Infection 
cause 
Culture 
identified 
organisms 
Was an 
antibiotic 
used to 
treat the 
infection? 
Was G-CSF 
used to treat 
the 
infection? 
Was Ig used 
to treat the 
infection? 
Area of 
Infection 
Did the 
infection 
require a visit 
to a doctor's 
office? 
100  
100  
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
25  
200  
 
 
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
 
100  
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
300  
 
 
 
 
 
 
 
 
 
 
 
400  
 
 
 
 
 
 
 
 
 
Abbreviations: AE = Adverse event; ER = Emergency Room. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
Programming Note: Sort Adverse Events by Patient, Start Date, System Organ Class and Preferred Term 
Only include infections where SOC = Infections and infestations 
 
 


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Page 148 of 172 
Listing 16.2.7.3 
Infections Reported as Adverse Events  
Safety Population 
 
Subject 
Number 
AE # 
Number of 
doctor's office 
visits due to 
infection 
Did the 
infection 
require 
hospital 
admission? 
Number of 
days in 
hospital due 
to infection 
Did the 
infection 
require a 
visit to 
the ER? 
Did the 
infection 
require 
admission to 
an intensive 
care unit? 
Number of 
Days of 
work/school 
missed 
Were there 
fevers 
associated with 
the infection? (if 
Y, Peak Fever 
Temperature (C) 
Fever Start Date(Day)/ 
End Date(Day) [1] 
 
 
 
 
 
 
 
 
DDMMMYYYY(XX)/ 
DDMMMYYYY(XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: ER = Emergency Room. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
Programming Note: Sort Adverse Events by Patient, Start Date, System Organ Class and Preferred Term 
Only include infections where SOC = Infections and infestations 
 
 
 


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Confidential 
 
 
 
 
 
Page 149 of 172 
Listing 16.2.7.4 
Deaths 
All Enrolled Patients 
 
Subject Number 
Capsule Strength 
(mg) 
Dose Level (mg) 
Date of 
Death (Day) [1] 
25  
100  
 
 
 
 
100  
300  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
[1] Day is calculated as (assessment  date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as 
(assessment date – date of administration of first study drug) if prior to the administration of first study drug. 
 
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 150 of 172 
Listing 16.2.7.5 
Treatment Limiting Toxicities  
Safety Population 
Subject 
Number 
Capsule 
Strength 
(mg) 
Dose 
Level (mg) 
Gender 
 
Age 
System Organ Class/ 
 Preferred Term/ 
  Verbatim Term 
Start Date(Day)/ 
 End Date(Day) [1] 
Severity [2]/  
Relationship [3] 
Outcome/  
 Action Taken 
25  
100  
M 
56 
 
DDMMMYYYY(XX)/ 
 DDMMMYYYY(XX) 
 
 
 
 
 
 
 
 
 
 
 
100  
F 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
200  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: A TLT event for X4P-001 is defined as an AE that meets both of the following criteria: 
1. 
Is assessed by the Investigator as possibly or probably related to X4P-001. 
2. 
Represents one of the following events (grading as defined by the NCI CTCAE, v4.03 or higher): 
- 
Is a Grade 3 or Grade 4 clinical event, except 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 with the following exceptions: Grade 3 electrolyte abnormalities that persist <72 hrs and do not require hospitalization. 
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). 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] Severity is assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (v4.03).  
[3] Related = definitely related, probably related and possibly related; Unrelated = Unlikely related, not related 
 
Programming Note: Sort Adverse Events by System Organ Class and Preferred Term; Footne the criteria for identifying the TLT 
 
 


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Page 151 of 172 
Listing 16.2.7.6 
Infections in Subjects Treated on 300mg or 400 mg Dose by Time Period  
Safety Population  
Subject Number 
Time Period    
Number of Infections  
 
 
 
 
Pre-Study (12 months prior to first dose) 
xx 
 
 
 
 
0-6 Months 
xx 
 
 
 
 
6-12 Months  
xx 
 
 
 
 
……. 
 
 
 
 
 
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections are 
identified as all events with a MedDRA System Organ Class of “Infections and infestations”.. The reporting period starts on the 300 mg dose date. Only events with start date occurring 
within start and end dates of 300/400 mg dose for each patient are included. Time period assignment is based on the start date of the event. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
 
Programming Note: Complete table until maximum duration in 6 month intervals; For the two patients re-enrolled, we need add “drop out period”, “6 Months after 
re-enrollment”, 6 – 12 Months after re-enrollment”,…. 
present all data including data after re-enrollment for the 2 re-enrolled patients 
 
 
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 152 of 172 
Listing 16.2.7.7 
Infections by Dose Level 
Safety Population 
Subject Number 
Dose Level    
Number of Infections 
Yearly Rate  
 
 
 
 
50/100/150 mg 
xx 
xx 
200 mg 
xx 
xx 
300 mg  
xx 
xx 
300 mg 
xx 
xx 
400 mg 
xx 
xx 
300/400 mg 
xx 
xx 
 
 
 
… 
 
 
 
 
 
 
Notes: Infections are identified as follows: for Prior 12 months, events are identified from the Medical History CRF. While on study, infections are identified as all events with a 
MedDRA System Organ Class of “Infections and infestations”. Events at dose level are assigned based on the start date of the event occurring within start and end dates of that dose. 
Rate is defined as number of infection events in a given dose level / duration of exposure on a dose level in years. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
 
Programming Note: present all data including data after re-enrollment for the 2 re-enrolled patients 
 
 


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Page 153 of 172 
Listing 16.2.7.8 
Infections by Subject  
Safety Population  
 
Infection Details [1] 
 
 
Subject 
Number 
Date of 
Consent 
Dose 
Level (mg) 
Treatment 
Start Date 
Treatment 
End Date 
Duration 
(Days)  
at Dose Level 
Number 
of 
Infections 
AE Start 
Date 
AE End 
Date 
Preferred Term/ 
AE Term 
Infection  
Severity 
 
DDMMMYYYYPrior 12 
months 
         
         
   
5 
DDMMMYYYY --/---/---- 
/Cellulitis 
Grade X 
DDMMMYYYY DDMMMYYYY /Otitis media 
Grade X 
DDMMMYYYY DDMMMYYYY /Pneumonia 
Grade X 
DDMMMYYYY DDMMMYYYY /Skin abscesses 
Grade X 
DDMMMYYYY DDMMMYYYY /URI (sinusitis, otitis, pharyngitis) 
Grade X 
50  
DDMMMYYYY DDMMMYYYY 37 
4 
DDMMMYYYY DDMMMYYYY Ear infection/ear inflammation causing 
discomfort 
Grade X 
DDMMMYYYY DDMMMYYYY Sinusitis/sinus inflammation causing  
discomfort 
Grade X 
DDMMMYYYY DDMMMYYYY Ear infection/Ear infection 
Grade X 
DDMMMYYYY DDMMMYYYY Sinusitis/sinus infection 
Grade X 
100  
DDMMMYYYY DDMMMYYYY 52 
0 
150  
DDMMMYYYY DDMMMYYYY 145 
0 
300  
DDMMMYYYY DDMMMYYYY 126 
2 
DDMMMYYYY DDMMMYYYY Sinusitis/Sinus infection 
Grade X 
DDMMMYYYY DDMMMYYYY Sinusitis/Sinusitis 
Grade X 
400 
DDMMMYYYY DDMMMYYYY 513 
4 
DDMMMYYYY DDMMMYYYY Pharyngitis/Pharyngitis 
Grade X 
DDMMMYYYY DDMMMYYYY Otitis media acute/Acute suppurative 
otitis media 
Grade X 
DDMMMYYYY DDMMMYYYY Sinusitis/Sinusitis 
Grade X 
DDMMMYYYY 
Cellulitis/Cellulitis (left forearm) 
Grade X 
400 (after re-
enrollment) 
DDMMMYYYY DDMMMYYYY XX 
XX 
DDMMMYYYY DDMMMYYYY xxxxxxxxxxxxx 
  
 
 
DDMMMYYYYPrior 12 
months 
         
         
   
5 
DDMMMYYYY DDMMMYYYY /Abscess, left leg/thigh 
Grade X 
DDMMMYYYY DDMMMYYYY /Cellulitis at skin biopsy site - left side 
of neck 
Grade X 
DDMMMYYYY DDMMMYYYY /Cellulitis at skin biopsy site - right arm Grade X 
DDMMMYYYY DDMMMYYYY /Cellulitis, left external ear 
Grade X 
DDMMMYYYY DDMMMYYYY /Cellulitis, left forearm 
Grade X 


X4 Pharmaceuticals, Inc.  
Statistical Analysis Plan (SAP) X4P-001-MKKA  
Confidential 
 
 
 
 
 
Page 154 of 172 
 
Infection Details [1] 
 
 
Subject 
Number 
Date of 
Consent 
Dose 
Level (mg) 
Treatment 
Start Date 
Treatment 
End Date 
Duration 
(Days)  
at Dose Level 
Number 
of 
Infections 
AE Start 
Date 
AE End 
Date 
Preferred Term/ 
AE Term 
Infection  
Severity 
Abbreviation: AE = Adverse event. 
[1] Infections identified as follows: for Prior 12 months, events are identified from the Medical History CRF under History of WHIM infections. While on study, infections 
are identified as all events with a MedDRA System Organ Class of ‘Infections and infestations’; dose level is assigned based on the start date of the event occurring 
within start and end dates of that dose for each subject. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
Patient 
 was re-enrolled into the study on DDMMMYYYY. 
 
Programming note: Present all dose levels with start and end dates available. If patient didn’t have any infection events, then the number of infections is 0. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Page 155 of 172 
Listing 16.2.8.1 
Clinical Laboratory Data: Serum Chemistry 
Safety Population 
 
Test Name: XXXXX (units) 
Subject 
Number 
Visit 
Dose 
Level 
(mg) 
Date/Time of 
Assessment (Day) [1]  
Standard 
Results 
Reference 
Range 
Abnormal?/ 
High/Low [2] 
Change 
from 
Baseline [3] 
Calculated 
CTC Grade 
Comments/ 
Reason not Done 
Day 1 
100  
DDMMMYYYY/ 
HH:MM (XX) 
XX 
XX - XX 
No 
 
 
 
Week 5 
100 
 
 
 
 
 
 
 
Week 13 
200 
 
 
 
 
 
 
 
Week 21 
300 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
100 
 
 
 
 
 
 
 
Week 5 
100 
 
 
 
 
 
 
 
Week 13 
100 
 
 
 
 
 
 
 
Week 21 
200 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
200 
 
 
 
 
 
 
 
 
Week 5 
200 
 
 
 
 
 
 
 
 
Week 13 
300 
 
 
 
 
 
 
 
 
Week 21 
400 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] L = Low, H = High. 
[3] Change from baseline = value - Baseline value. Baseline is defined as the last assessment prior to the first study drug. 
 
 


X4 Pharmaceuticals, Inc.  
Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 156 of 172 
Listing 16.2.8.2 
Clinical Laboratory Data: Hematology 
Safety Population 
 
(Same shell as Listing 16.2.8.1) 
 
 
 
 
Listing 16.2.8.3 
Serology and Other Laboratory Test Results 
Safety Population 
 
(Same shell as Listing 16.2.8.1) 
 
 
 
 


X4 Pharmaceuticals, Inc.  
Statistical Analysis Plan (SAP) X4P-001-MKKA  
Confidential 
 
 
 
 
 
Page 157 of 172 
Listing 16.2.8.4 
Serum Ig and Specific Antibody Laboratory Test Results 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
strength 
(mg) 
Dose 
Level 
(mg) 
Date/Time Collected 
(Day) [1]  
Test Name 
Standard Results 
Reference 
Range 
CFB 
[2] 
Fold- 
Change  
Flag 
[3] 
 
Day 1 
25 
100 
DDMMMYYYY/HH:MM (XX) 
Haemophilus Influenzae B 
Polysaccharide (mg/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin A (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin G (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin G Subclass 1 (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin G Subclass 2 (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin G Subclass 3 (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin G Subclass 4 (g/L) 
 
 
 
 
 
 
 
 
 
 
Immunoglobulin M (g/L) 
 
 
 
 
 
 
 
 
 
 
Rubeola IgG (Measles) 
Positive/Negative 
 
 
 
 
 
 
 
 
 
Rubella IgG Antibody Index 
(INDEX) 
 
 
 
 
 
 
 
 
 
 
Tetanus Toxoid (IU/L) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week X 
25 
200  
DDMMMYYYY/HH:MM (XX) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: CFB = Change from Baseline. 
Fold-Change = Value/Baseline 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] Change from Baseline = value - baseline value. Baseline is defined as the last assessment prior to the first study drug. 
[3] L = Low, H = High, N = Normal. 
 
  
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 158 of 172 
Listing 16.2.8.5 
Pregnancy Test 
Safety Population 
 
Subject 
Number 
Visit 
Dose Level 
(mg) 
Was Pregnancy Test 
Performed?     
Date Performed (Day) 
[1] 
Time of 
Assessment 
Specimen Type 
Result of Pregnancy 
Test 
Screening 
100 
Yes 
DDMMMYYYY(XX) 
HH:MM 
Serum 
<5 (IU/L)/Negative 
 
 
 
 
 
Urine 
Negative 
Week X/ 
100 
Yes 
DDMMMYYYY(XX) 
HH:MM 
Serum 
<5 (IU/L)/Negative 
… 
 
 
 
 
Urine 
Negative 
 
 
 
 
 
 
 
Screening 
100 
Yes 
DDMMMYYYY(XX) 
HH:MM 
Serum 
<5 (IU/L)/Negative 
 
 
 
 
 
Urine 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
200 
Yes 
DDMMMYYYY(XX) 
HH:MM 
Serum 
<5 (IU/L)/Negative 
 
 
 
 
 
 
Urine 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of administration 
of first study drug) if prior to the administration of first study drug. 
 
 


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Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 159 of 172 
Listing 16.2.8.6 
Coagulation Laboratory Test Results 
Safety Population 
Test Name: XXXXXXX (units)                                                                                                                                                             
 
Dose 
 
Change from 
Fold- 
Subject 
Number 
Visit 
Level  
(mg) 
Date/Time of  
Assessment (Day) [1] 
Test Result 
Reference  
Range 
Abnormal?  
High/Low [2] 
Baseline  
[3] 
Change  
[4] 
 
Week 9 
XXX 
DDMMMYYYY/HH:MM (XX) 
XX.X 
XX - XX 
Yes / H 
 
 
Week 13 
XXX 
 
XX.X 
XX - XX 
No 
 
 
Week 17 
XXX 
 
XX.X 
XX - XX 
Yes / H 
 
 
Week 21 
XXX 
 
XX.X 
XX - XX 
No 
 
 
 
Week 9 
XXX 
 
XX.X 
XX - XX 
No 
 
 
Week 13 
XXX 
 
XX.X 
XX - XX 
No 
 
 
Week 17 
XXX 
 
XX.X 
XX - XX 
No 
 
 
Week 21 
XXX 
 
XX.X 
XX - XX 
No 
 
 
 
Screening 
 
 
 
 
 
 
 
 
Day 1 
 
 
XX.X 
XX - XX 
No 
 
 
 
Week 2 
XXX 
 
XX.X 
 
 
 
 
 
Week 3 
XXX 
 
XX.X 
XX - XX 
No 
XX.X 
XX.X 
 
Week 4 
XXX 
 
XX.X 
XX - XX 
No 
XX.X 
XX.X 
 
Week 5 
XXX 
 
XX.X 
XX - XX 
No 
XX.X 
XX.X 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
   administration of first study drug) if prior to the administration of first study drug. 
[2] L = Low, H = High. 
[3] Change from Baseline = value - Baseline value. Baseline is defined as the last assessment prior to the first study drug. 
[4] Fold-Change = Value/Baseline. 


X4 Pharmaceuticals, Inc.  
Statistical Analysis Plan (SAP) X4P-001-MKKA  
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Page 160 of 172 
Listing 16.2.8.7 
Urinalysis Laboratory Test Results 
Safety Population  
Test Name: XXXXXX                                                                                                                                                                                               
Subject 
Number 
Visit 
Dose Level  
(mg) 
Date/Time of  
Assessment (Day) [1] 
Test Result 
Reference  
Range 
Abnormal?  
High/Low [2] 
Change from 
Baseline [3] 
Fold-Change  
[4] 
 
Screening 
 
DDMMMYYYY/HH:MM (XX) 
XXXXXX 
 
No 
 
 
Day 1 
 
DDMMMYYYY/HH:MM (XX) 
XXXXXX 
 
No 
 
 
Week 13 
XXX 
DDMMMYYYY/HH:MM (XX) 
XXXXXX 
 
No 
 
 
Week 21 
XXX 
DDMMMYYYY/HH:MM (XX) 
XXXXXX 
 
No 
 
 
 
Screening 
 
 
XXXXXX 
 
No 
 
 
Day 1 
 
 
XXXXXX 
 
No 
 
 
Week 13 
XXX 
 
XXXXXX 
 
No 
 
 
Week 21 
XXX 
 
XXXXXX 
 
No 
 
 
 
Screening 
 
 
XXXXXX 
 
No 
 
 
Day 1 
 
 
XXXXXX 
 
No 
 
 
Week 5 
XXX 
 
XXXXXX 
 
No 
 
 
 
Screening 
 
 
XXXXXX 
 
No 
 
 
 
Day 1 
 
 
XXXXXX 
 
No 
 
 
 
Week 5 
XXX 
 
XXXXXX 
 
No 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] L = Low, H = High. 
[3] Change from Baseline = value - Baseline value. Baseline is defined as the last assessment prior to the first study drug. 
[4] Fold-Change = Value/Baseline. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Page 161 of 172 
Listing 16.2.8.8 
CytometryTest Results 
Safety Population  
Test Name: XXXXXX                                                                                                                                                                                               
Subject 
Number 
Visit 
Dose Level  
(mg) 
Date/Time of  
Assessment (Day) [1] 
Replicate 
Test Result 
Change from 
Baseline [2] 
 
 
Screening 
 
DDMMMYYYY/HH:MM (XX) 
A 
XXXXXX 
XXXXXX 
 
 
DDMMMYYYY/HH:MM (XX) 
B 
XXXXXX 
XXXXXX 
 
 
DDMMMYYYY/HH:MM (XX) 
C 
XXXXXX 
XXXXXX 
Day 1 
 
DDMMMYYYY/HH:MM (XX) 
X 
XXXXXX 
XXXXXX 
Week 13 
XXX 
DDMMMYYYY/HH:MM (XX) 
X 
XXXXXX 
XXXXXX 
Week 21 
XXX 
DDMMMYYYY/HH:MM (XX) 
X 
XXXXXX 
XXXXXX 
 
Screening 
 
 
X 
XXXXXX 
XXXXXX 
 
Day 1 
 
 
X 
XXXXXX 
XXXXXX 
 
Week 13 
XXX 
 
X 
XXXXXX 
XXXXXX 
 
Week 21 
XXX 
 
X 
XXXXXX 
XXXXXX 
 
 
Screening 
 
 
X 
XXXXXX 
XXXXXX 
 
Day 1 
 
 
X 
XXXXXX 
XXXXXX 
 
Week 5 
XXX 
 
X 
XXXXXX 
XXXXXX 
 
 
Screening 
 
 
X 
XXXXXX 
XXXXXX 
 
 
Day 1 
 
 
X 
XXXXXX 
XXXXXX 
 
 
Week 5 
XXX 
 
X 
XXXXXX 
XXXXXX 
 
 
Note:  Each sample was run 3 times producing triplicate results A, B, C for each laboratory test.  
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] Change from Baseline = value - Baseline value. Baseline is defined as the last assessment prior to the first study drug. 
 
 


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Page 162 of 172 
Listing 16.2.9.1 
Prior or Concomitant Medications 
Safety Population 
 
Subject 
Number 
Prior, 
Concomitant 
or Both? 
ATC Class (Level 5)/  
 PT (ATC Level 4)/   
   VT 
Start Date (Day)/ 
 End Date (Day) [1] 
Dose 
 (Unit) 
Route 
Frequency 
Reason for Use 
 
 
Both 
XXXXXXXXXXXXXX/  
XXXXXXXXXXXXX/  
XXXXXXXXXXXXXXXXXXX 
Ongoing 
XX (mg) 
ORAL 
OTHER  
 (QD, PRN) 
Seasonal allergies 
 
 
Concomitant 
XXXXXXXXXXXXXX/  
XXXXXXXXXXXXX/  
XXXXXXXXXXXXXXXXXXX 
DDMMMYYYY (XX)/  
  DDMMMYYYY (XX) 
 
ORAL 
QD 
Seasonal allergies 
 
 
Prior 
XXXXXXXXXXXXXX/  
XXXXXXXXXXXXX/  
XXXXXXXXXXXXXXXXXXX 
DDMMMYYYY (XX)/  
  DDMMMYYYY (XX) 
ORAL 
QD 
body aches and 
pains 
 
Abbreviations: ATC = Anatomic Therapeutic Chemical; PT = Preferred Term; VT = Verbatim Term. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
Prior medication is any medication that is started or ended prior to the first dose of the study medication. 
Concomitant medication is any medication taken or ongoing on or after the first dose of the study medication. 
 
Programming Note: Sort Concomitant Medications by ATC Class and Preferred Term 
 
 


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Page 163 of 172 
Listing 16.2.9.2 
Vital Signs Measurements 
Safety Population 
 
Subject 
number 
Visit 
Capsule 
strength 
(mg) 
Dose 
Level 
(mg) 
Date of 
Assessment(Day)[1] 
Body 
Temp 
(C) 
Pulse 
Rate 
(bpm) 
Blood Pressure 
(mmHg) 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m2) [2] 
Systolic 
Diastolic 
 
Day 1 
25 
100 
DDMMMYYYY (XX)  
XX.X 
XX 
XX 
XX 
XX 
XX 
XX 
 
Week 5 
 
100 
 
XX.X 
XX 
XX 
XX 
XX 
XX 
XX 
 
Week 13 
 
200 
 
XX.X 
XX 
XX 
XX 
XX 
XX 
XX 
 
Week 21 
 
300 
 
XX.X 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: BMI = Body Mass Index. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
[2] BMI = Weight/(Height)2x104. 
 
 


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Page 164 of 172 
Listing 16.2.9.3 
12-Lead Electrocardiograms 
Safety Population  
 
Subject Number 
Visit 
Date of Assessment (Day) [1]  
 
Assessment 
Investigator Interpretation/Results 
 
 
 
 
 
 
Day 1 
DDMMMYYYY (XX) 
Summary (Mean) Heart Rate 
XX beats/min 
 
 
 
Summary (Mean) PR Duration 
XXX ms 
 
 
 
Summary (Mean) QRS Duration 
XXX ms 
 
 
 
Summary (Mean) QT Duration 
XXX ms 
 
 
 
QTc Interval 
XXX ms 
 
 
 
Interpretation 
N 
 
 
 
QTc Method 
Bazett's formula 
 
 
 
 
 
 
Week 5 
DDMMMYYYY (XX)  
…. 
 
 
 
 
… 
 
 
 
 
 
 
Abbreviations: CS = Clinically significant; NCS = Not clinically significant; N = Normal. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
 
 


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Page 165 of 172 
Listing 16.2.9.4 
Physical Examinations 
Safety Population 
 
Subject Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Performed? 
Date/Time of 
Examination (Day) [1]  
 
Body System 
Result 
Clinically 
Significant? 
Abnormal Findings 
Day 1 
 
100 
 
DDMMMYYYY (XX) 
Cardiovascular 
NORMAL 
 
 
Week 5 
25 
100 
 
 
Respiratory 
 
 
 
Week 13 
 
200 
 
 
Gastrointestinal 
ABNORMAL 
Yes/No 
 
Week 21 
 
300 
 
 
Neurological 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
100 mg 
 
 
Musculoskeletal 
NOT DONE 
 
 
Week 5 
 
100 mg 
 
 
HEENT 
 
 
 
Week 13 
 
100 mg 
 
 
Thyroid 
 
 
 
Week 21 
 
200 mg 
 
 
Skin 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
200 mg 
 
 
Extremities 
 
 
 
 
Week 5 
 
200 mg 
 
 
Genitourinary 
 
 
 
 
Week 13 
 
300 mg 
 
 
Other: XXXXXX 
 
 
 
 
Week 21 
 
400 mg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug.  
 
 
 
 


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Page 166 of 172 
Listing 16.2.9.5 
Ophthalmologic Examination (Site Assessment) 
Safety Population 
 
 
 
Centered On  
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose Level 
(mg) 
Performed? 
Date/Time of 
Examination (Day) 
[1] 
Photos 
Collected 
During the 
Retinal 
Exam? 
Results 
 
Optic 
Nerve 
Macula 
Superior 
Arcade 
Inferior 
Arcade 
Temporal 
Retina (2 
photos) 
Nasal 
Retina 
 
 
Part A - 
Screening 
 
 
Yes 
DDMMMYYYY/ 
HH:MM (XX) 
Yes 
Abnormal 
- NCS 
 Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
Part A - 
Week 13 
25 
100 
Yes 
DDMMMYYYY/ 
HH:MM (XX) 
Yes 
Abnormal 
- NCS 
 Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
Part A - 
Week 25 
EOT 
25 
150 
Yes 
DDMMMYYYY/ 
HH:MM (XX) 
Yes 
Abnormal 
- NCS 
 Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
Bilateral 
 
 
No 
 
 
 
  
 
 
 
 
 
 
Abbreviations: CS = Clinically significant; NCS = Not clinically significant. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of administr
ation of first study drug) if prior to the administration of first study drug. 
 
 


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Page 167 of 172 
Listing 16.2.9.6 
Ophthalmologic Examination (Central Readings) 
Safety Population 
 
Subject 
Number 
Visit 
Date of 
examination 
(Day) [1] 
Photographs 
Reviewed? 
Retinal Findings 
Agree 
with 
Local 
Results? 
Disagreement 
Description 
Any 
Photograph 
Deficiencies? 
Retinal 
Photograph 
Deficiencies 
Other 
Findings or 
Concerns? 
Non-
Retinal 
Findings 
Day 1 
 
 
 
 
 
 
 
 
 
Week 5 
DDMMYYYY 
(XX) 
Yes 
Abnormal - new 
finding NCS 
No 
 
No 
 
No 
 
Week 13 
 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
 
 
 
 
Week 5 
 
 
 
 
 
 
 
 
 
 
Week 13 
 
 
 
 
 
 
 
 
 
 
Week 21 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
 


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Page 168 of 172 
Listing 16.2.9.7 
Rescue Medications 
Safety Population 
 
Subject Number 
Did subject receive rescue therapy for acute, 
severe bacterial infection while on study? 
Medication 
Record Number 
Start date/Time (Day)/ 
End Date/Time (Day)[1]  
Ongoing? 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Day is calculated as (start/end date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (start/end date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
  
 


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Page 169 of 172 
Listing 16.2.9.8 
SF-36 QOL 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Was the SF-36 
QOL 
Questionnaire 
Completed? 
Date of Questionnaire 
completion (Day) [1] 
Physical 
Functioning 
(PF) Domain 
Score 
Role-Physical 
(RP) Domain 
Score 
Bodily Pain 
(BD) Domain 
Score 
General 
Health (GH) 
Domain Score 
Vitality (VT) 
Domain Score 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
 
No 
 
 
 
 
 
 
 
Week 3 
25 
50 
Yes 
DDMMMYYYY (XX) 
90 
75 
74 
25 
43.75 
 
Week 5 
25 
50 
Yes 
DDMMMYYYY (XX) 
90 
81.25 
74 
30 
37.5 
 
Week 9 
25 
100 
Yes 
DDMMMYYYY (XX) 
95 
75 
62 
35 
37.5 
 
Week 13 
25 
100 
Yes 
DDMMMYYYY (XX) 
90 
93.75 
84 
35 
37.5 
 
Week 17 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
30 
50 
 
Week 21 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
30 
62.5 
 
Week 25 
EOT 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
45 
68.75 
 
Extension 
Phase - 
Residence 
Visit 1 
Post EOS 
100 
300 
Yes 
DDMMMYYYY (XX) 
100 
100 
84 
30 
62.5 
 
Extension 
Phase - 
Residence 
Visit 1 
100 
300 
Yes 
DDMMMYYYY (XX) 
100 
100 
100 
37 
62.5 
 
Extension 
Phase - 
Residence 
Visit 2 
100 
400 
Yes 
DDMMMYYYY (XX) 
100 
100 
62 
30 
56.26 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: QOL = Quality of Life. 
[1] Day is calculated as (collection date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (collection date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
  
 


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Page 170 of 172 
Listing 16.2.9.8 
SF-36 QOL 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Was the 
SF-36 QOL 
Questionnaire 
Completed? 
Date of 
Questionnaire 
completion (Day) [1] 
Social 
Functioning 
(SF) Domain 
Score 
Role- 
Emotional 
(RE) 
Domain 
Score 
Mental 
Health (MH) 
Domain 
Score 
Reported 
Health 
Transition 
(HT) Item 
Score 
Physical 
Component 
Summary 
(PSC) 
Score 
Mental 
Component 
Summary 
(MCS) 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
 
 
No 
 
 
 
 
 
 
 
 
Week 3 
25 
50 
Yes 
DDMMMYYYY (XX) 
90 
75 
74 
25 
43.75 
 
 
Week 5 
25 
50 
Yes 
DDMMMYYYY (XX) 
90 
81.25 
74 
30 
37.5 
 
 
Week 9 
25 
100 
Yes 
DDMMMYYYY (XX) 
95 
75 
62 
35 
37.5 
 
 
Week 13 
25 
100 
Yes 
DDMMMYYYY (XX) 
90 
93.75 
84 
35 
37.5 
 
 
Week 17 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
30 
50 
 
 
Week 21 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
30 
62.5 
 
 
Week 25 
EOT 
25 
150 
Yes 
DDMMMYYYY (XX) 
90 
100 
84 
45 
68.75 
 
 
Extension 
Phase - 
Residence 
Visit 1 
Post EOS 
100 
300 
Yes 
DDMMMYYYY (XX) 
100 
100 
84 
30 
62.5 
 
 
Extension 
Phase - 
Residence 
Visit 1 
100 
300 
Yes 
DDMMMYYYY (XX) 
100 
100 
100 
37 
62.5 
 
 
Extension 
Phase - 
Residence 
Visit 2 
100 
400 
Yes 
DDMMMYYYY (XX) 
100 
100 
62 
30 
56.26 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviation: QOL = Quality of Life. 
[1] Day is calculated as (exam date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (exam date - date of 
administration of first study drug) if prior to the administration of first study drug. 
 
 


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Page 171 of 172 
Listing 16.2.9.9.1 
HPV Impact Profile (HIP) Questionnaire 
Safety Population 
 
Subject 
Number 
Visit 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Collection Date 
(Day) [1] 
Does the 
Subject 
have 
Genital 
Warts? 
HIP 
Questi- 
onnaire 
Colle- 
cted? 
Question 
Subject 
Response 
Subject 
Response 
Description 
 
 
XXXXXXXXXX 
XX 
XXX 
DDMMMYYYY (XX) Yes 
Yes 
1. When I think about my recent 
gynecology exam or test results, I feel 
good about myself. 
X 
XXXXXX 
 
 
 
 
 
 
 
2. When I think about my recent 
gynecology exam or test results, I feel 
anxious. 
X 
XXXXXX 
 
 
 
 
 
 
 
3. I feel my recent gynecology test results 
were unexpected. 
X 
XXXXXX 
 
 
 
 
 
 
 
4. When I think about my recent 
gynecology exam or test results, I feel in 
control of my health. 
X 
XXXXXX 
 
 
 
 
 
 
 
5. When I think about my recent 
gynecology exam or test results, I feel 
depressed. 
X 
XXXXXX 
 
 
 
 
 
 
 
6. After my recent gynecology exam or 
test results, I feel I can concentrate as well 
as usual on everyday matters. 
X 
XXXXXX 
 
 
 
 
 
 
 
7. When I think about my recent 
gynecology exam or test results, I feel 
something is seriously wrong with me. 
X 
XXXXXX 
 
 
 
 
 
 
 
8. When I think about my recent 
gynecology exam or test results, I feel 
angry. 
X 
XXXXXX 
 
[1] Day is calculated as (collection date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (collection date - date of  
administration of first study drug) if prior to the administration of first study drug. 
 
 
 


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Page 172 of 172 
Listing 16.2.9.9.2 
HPV Impact Profile (HIP) Questionnaire - Domain Scores 
Safety Population 
 
Subject 
Number 
Visit 
 
Capsule 
Strength 
(mg) 
Dose 
Level 
(mg) 
Collection Date 
(Day) [1] 
Does the 
Subject 
have 
Genital 
Warts? 
HIP 
Questi- 
onnaire 
Colle- 
cted? 
Domain 
Mean 
Transformed 
Score 
Overall 
Mean 
Transformed 
Score 
 
 
XXXXXXXX 
 
 
 
XXXXXXX 
Yes 
Yes 
Self Image 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
Emotional Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Control/Life Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Worries and Concerns 
XX.X 
 
 
 
 
 
 
 
 
 
Partner and Transmission 
XX.X 
 
 
 
 
 
 
 
 
 
Sexual Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Interactions with Doctors 
XX.X 
 
 
 
Part A - Day 1 
 
 
 
 
Yes 
No 
 
 
 
 
 
Part A - Week 3 
 
XX 
XXX 
XXXXXXX 
Yes 
Yes 
Self Image 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
Emotional Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Control/Life Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Worries and Concerns 
XX.X 
 
 
 
 
 
 
 
 
 
Partner and Transmission 
XX.X 
 
 
 
 
 
 
 
 
 
Sexual Impact 
XX.X 
 
 
 
 
 
 
 
 
 
Interactions with Doctors 
XX.X 
 
 
[1] Day is calculated as (collection date - date of administration of first study drug) + 1 if on or after the administration of first study drug. Day is calculated as (collection date - date of a
dministration of first study drug) if prior to the administration of first study drug.