Clinical trial NCT05293171
Conditions: Healthy Subjects
Sponsor: BioLineRx, Ltd.
Start date: 2021-06-11; Completion date: 2022-08-15
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The study will assess the corrected QT (QTc) effects (electrocardiogram \[ECG\]) of motixafortide (BL-8040) 1.25 mg/kg (therapeutic dose) and 2 mg/kg (supratherapeutic dose) following a single subcutaneous (SC) injection relative to placebo in approximately 40 healthy subjects.

Detailed description:
This is a randomized, double-blind (in respect to BL-8040 and BL-8040-matching placebo dosing), placebo- and positive-controlled, 4-period, 4-way crossover study in healthy subjects.

A continuous 12-lead cardiodynamic ECG recording will be collected for approximately 24 hours on Day -1 of Period 1 for use in the optimized individual corrected QTc (QTcI) baseline calculations.

On Day 1 of Period 1, subjects will be randomized to 1 of 12 treatment sequences. Each treatment sequence comprises 4 treatment periods.

On Day 1 of each period, subjects will receive single-dose SC injection of BL-8040 (therapeutic or supratherapeutic dose), single-dose SC injection of BL-8040-matching placebo, or a single oral dose of moxifloxacin. Cardiodynamic readings, plasma pharmacokinetic (PK) samples, and blood pharmacodynamic (PD) samples will be collected at different time points prior to dosing and up to 24 hours postdose in each period, as appropriate.

There will be a washout period of 5-7 days between dosing in each period.

All subjects who received at least one dose of any study drug (including subjects who terminate the study early) will return to the clinical research unit (CRU) 7 ± 2 days after the last dose for follow-up procedures, and to determine if any adverse event (AE) has occurred since the last study visit.

Arms: arm 1: 1.25 mg/kg BL-8040 + BL-8040-matching placebo administered via SC injection (Therapeutic) arm 2: 2 mg/kg BL-8040 administered via SC injection (Supratherapeutic) arm 3: BL-8040-matching placebo administered via SC injection arm 4: 400 mg moxifloxacin (1 x 400 mg tablet) administered orally
Interventions: intervention 1: 1.25 mg/kg BL-8040 + BL-8040-matching placebo intervention 2: 2 mg/kg BL-8040 intervention 3: BL-8040-matching placebo intervention 4: 400 mg Moxifloxacin (1x400 mg tablet)
Intervention descriptions: intervention 1: Administered via subcutaneous (SC) injection intervention 2: Administered via subcutaneous (SC) injection intervention 3: Administered subcutaneous (SC) injection intervention 4: Administered orally

Protocol documents:
Prot_SAP_000.pdf: 
 
BioLineRx.com 
Israel Headquarters 
Modi’in Technology Park 
2 HaMa’ayan Street 
Modi’in 7177871, Israel 
Phone: +972.8.642.9100  
 
 
 
NCT Number: 
NCT05293171 
Sponsor Study Number: 
BL-8040.TQT.103 
Official Study Title: 
Single-Dose, Randomized, Double-Blind, Placebo-Controlled, 
Positive-Controlled, Four-Way Crossover Study to Investigate 
the Effect of BL-8040 (Motixafortide) on the QTc Interval in 
Healthy Subjects 
Document Version and Date: 
Clinical Study Protocol, Amendment 2, 30 June 2021  


 
 
Page 1 
 
 
 
 
 
 
Clinical Protocol 
 
A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Positive-Controlled, 
Four-Way Crossover Study to Investigate the Effect of BL-8040 (Motixafortide) on the 
QTc Interval in Healthy Subjects 
 
 
 
 Project No.: CA33565 
 
 
Sponsor Project No.: BL-8040.TQT.103 
 
 
US IND No.: 
 
 
 
 
 
 
 
 
 
 
GCP Statement 
This study is to be performed in full compliance with the protocol, Good Clinical Practices 
(GCP), and applicable regulatory requirements. All required study documentation will be 
archived as required by regulatory authorities. 
 
Confidentiality Statement 
This document is confidential. It contains proprietary information of BioLineRx Ltd. 
and/or 
 Any viewing or disclosure of such information that is not authorized in 
writing by BioLineRx Ltd. and/or 
 is strictly prohibited. Such information may be 
used solely for the purpose of reviewing or performing this study. 
 


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PROTOCOL REVISION HISTORY 


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PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES 
A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Positive-Controlled, 
Four-Way Crossover Study to Investigate the Effect of BL-8040 (Motixafortide) on the 
QTc Interval in Healthy Subjects 
 
 
 
 
Signature:   
 
Date: _________________ 
 
 
 
 
 


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A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Positive-Controlled, 
Four-Way Crossover Study to Investigate the Effect of BL-8040 (Motixafortide) on the 
QTc Interval in Healthy Subjects 
 
 
SPONSOR AND SPONSOR’S REPRESENTATIVES: 
BioLineRx Ltd. 
Date: _________________ 
 
 
30 June 21


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ADDITIONAL KEY CONTACTS FOR THE STUDY 


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TABLE OF CONTENTS 
1 PROTOCOL REVISION HISTORY ............................................................................. 2 
2 PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES ......................... 4 
3 ADDITIONAL KEY CONTACTS FOR THE STUDY ................................................ 6 
4 TABLE OF CONTENTS ................................................................................................. 8 
5 SYNOPSIS ....................................................................................................................... 12 
6 STUDY EVENTS FLOW CHART ............................................................................... 15 
7 ABBREVIATIONS ......................................................................................................... 19 
8 INTRODUCTION........................................................................................................... 23 
8.1 
BL-8040 (Motixafortide) ......................................................................................... 23 
8.1.1 
Nonclinical Pharmacology and Pharmacokinetics .................................... 23 
8.1.2 
Nonclinical Toxicology ............................................................................ 27 
8.1.3 
Nonclinical Safety Pharmacology............................................................. 28 
8.1.3.1 
Cardiovascular System Assessment ......................................... 28 
8.1.4 
Clinical Data ............................................................................................. 29 
8.1.5 
Pharmacokinetics in Humans .................................................................... 31 
8.1.6 
Safety Data in Human ............................................................................... 37 
8.1.7 
Human Cardiac Safety .............................................................................. 38 
8.2 
Moxifloxacin ........................................................................................................... 38 
8.3 
Rationale .................................................................................................................. 39 
8.3.1 
Rationale for this Study and Study Design ............................................... 39 
8.3.2 
Rationale for the Dose Selection ............................................................... 39 
8.3.3 
Rationale for Premedication Selection ...................................................... 40 
8.4 
Risks and/or Benefits to Subjects ............................................................................ 40 
9 OBJECTIVES AND ENDPOINTS ............................................................................... 42 
10 STUDY DESIGN ............................................................................................................. 43 
10.1 Overall Study Design and Plan ............................................................................... 43 
10.1.1 
Confinement and Follow-Up .................................................................... 43 
10.1.2 
End of Study Definition ............................................................................ 44 
11 STUDY POPULATION ................................................................................................. 45 
11.1 Inclusion Criteria ..................................................................................................... 45 
11.2 Exclusion Criteria .................................................................................................... 46 
11.3 Early Termination of Subjects from the Study ........................................................ 48 
11.4 Study Restrictions ................................................................................................... 49 
11.4.1 
Prohibitions ............................................................................................... 49 


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11.4.2 
Concomitant Medication ........................................................................... 49 
11.4.3 
Meals ......................................................................................................... 49 
11.4.4 
Activity ..................................................................................................... 50 
12 TREATMENTS............................................................................................................... 51 
12.1 Premedication Administered ................................................................................... 51 
12.2 Treatments Administered ........................................................................................ 51 
12.3 Dose Modification ................................................................................................... 52 
12.4 Treatment Compliance ............................................................................................ 52 
12.5 Method of Treatment Assignment and Treatment Sequence .................................. 53 
12.6 Blinding ................................................................................................................... 53 
12.6.1 
Maintenance of Randomization ................................................................ 53 
12.6.2 
Procedures for Breaking the Blind Prior to Study Completion ................ 54 
12.6.3 
Revealing of Randomization..................................................................... 54 
12.7 Rescue Medication .................................................................................................. 54 
13 STUDY ASSESSMENTS AND PROCEDURES ......................................................... 55 
13.1 Screening ................................................................................................................. 55 
13.2 Safety Assessments ................................................................................................. 55 
13.2.1 
Physical Examination................................................................................ 55 
13.2.2 
Vital Signs ................................................................................................. 56 
13.2.3 
ECG Monitoring ....................................................................................... 56 
13.2.3.1 12-Lead Safety ECGs ............................................................... 56 
13.2.3.2 Cardiodynamic ECGs .............................................................. 57 
13.2.3.2.1 TQT Plus ECG Extraction Technique ............................. 57 
13.2.3.2.2 Expert-Precision QT Analysis ......................................... 58 
13.2.3.2.3 Cardiodynamic ECG Assessment .................................... 58 
13.2.4 
Height, Body Weight, and BMI ................................................................ 59 
13.2.5 
Clinical Laboratory Tests .......................................................................... 60 
13.2.6 
Adverse Events ......................................................................................... 61 
13.2.6.1 Adverse Event Definition ......................................................... 61 
13.2.6.2 Monitoring ............................................................................... 61 
13.2.6.3 Reporting .................................................................................. 61 
13.2.6.4 Serious Adverse Event ............................................................. 62 
13.3 Pharmacokinetic Assessments ................................................................................. 62 
13.3.1 
Blood Sampling and Processing ............................................................... 62 
13.3.1.1 BL-8040 (Motixafortide) ......................................................... 62 
13.3.1.2 Moxifloxacin ............................................................................ 63 
13.3.2 
Pharmacokinetic Parameters ..................................................................... 63 
13.3.3 
Analytical Method .................................................................................... 64 


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13.4 Pharmacodynamic Assessments .............................................................................. 64 
13.5 Future Research ....................................................................................................... 64 
13.6 Blood Volume Drawn for Study Assessments ........................................................ 65 
14 STATISTICAL CONSIDERATIONS .......................................................................... 66 
14.1 Sample Size Determination ..................................................................................... 66 
14.1.1 
Sample Size Determination for Assay Sensitivity .................................... 66 
14.2 Population for Analyses .......................................................................................... 67 
14.3 Cardiodynamic Analyses ......................................................................................... 67 
14.4 Pharmacokinetic Analyses ...................................................................................... 67 
14.4.1 
Descriptive Statistics ................................................................................. 67 
14.5 Pharmacodynamic Analysis .................................................................................... 67 
14.6 Safety Analyses ....................................................................................................... 67 
15 STUDY ADMINISTRATION........................................................................................ 69 
15.1 Ethics ....................................................................................................................... 69 
15.1.1 
Institutional Review Board ....................................................................... 69 
15.1.2 
Ethical Conduct of the Study .................................................................... 69 
15.1.3 
Subject Information and Consent.............................................................. 69 
15.1.4 
Confidentiality .......................................................................................... 69 
15.2 Termination of the Study ......................................................................................... 70 
15.3 Data Quality Assurance ........................................................................................... 70 
15.4 Direct Access to Source Data/Documents .............................................................. 70 
15.5 Drug Supplies, Packaging and Labeling ................................................................. 70 
15.6 Data Handling and Record Keeping ........................................................................ 71 
15.7 Report Format ......................................................................................................... 71 
15.8 Publication Policy ................................................................................................... 71 
16 REFERENCES ................................................................................................................ 72 
 


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LIST OF TABLES 
Table 1: 
Summary of Day 1 BL-8040 Pharmacokinetic Parameters after 
Subcutaneous Administration in Subjects with Relapsed/Refractory 
Acute Myeloid Leukemia (Study BL-8040.01) ............................................. 33 
Table 2: 
Summary of Day 7 BL-8040 Pharmacokinetic Parameters after 
Subcutaneous Administration in Subjects with Relapsed/Refractory 
Acute Myeloid Leukemia (Study BL-8040.01) ............................................. 35 
Table 3: 
Mean (SD) Predose BL-8040 Concentrations (ng/mL) by Day 
(Study BL-8040.01) ....................................................................................... 37 
Table 4: 
Design of Treatment Sequences .................................................................... 53 
Table 5: 
Blood Volume During the Study ................................................................... 65 
 


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5 
SYNOPSIS 
Compound: 
BL-8040 (motixafortide) 
Study Title: 
A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, 
Positive-Controlled, Four-Way Crossover Study to Investigate the 
Effect of BL-8040 (Motixafortide) on the QTc Interval in Healthy 
Subjects 
Study Phase and 
Type: 
Phase I – cardiac liability study 
Study Objectives: 
Primary: 
To assess the corrected QT (QTc) effects (electrocardiogram [ECG]) 
of BL-8040 1.25 mg/kg (therapeutic dose) and 2 mg/kg 
(supratherapeutic dose) following a single subcutaneous (SC) 
injection relative to placebo in healthy subjects. 
Secondary: 
• To evaluate the safety, tolerability, and pharmacokinetics (PK) of 
single therapeutic and supratherapeutic SC injections of BL-8040 
in healthy subjects. 
• To assess the effects of single therapeutic and supratherapeutic 
SC injections of BL-8040 on non-QT interval ECG parameters 
(heart rate [HR], RR, PR, and QRS intervals) in healthy subjects. 
• To evaluate assay sensitivity (i.e., to evaluate the effect of a 
positive control, a single oral 400 mg dose of moxifloxacin, on 
the QTc interval in healthy subjects). 
Exploratory: 
To evaluate the pharmacodynamic (PD) effects of single therapeutic 
and supratherapeutic SC injections of BL-8040. 
Summary of Study 
Design: 
This is a randomized, double-blind (in respect to BL-8040 and 
BL-8040-matching placebo dosing), placebo- and positive-controlled, 
4-period, 4-way crossover study in healthy subjects. 
A continuous 12-lead cardiodynamic ECG recording will be 
collected for approximately 24 hours on Day -1 of Period 1 for use in 
the optimized individual corrected QTc (QTcI) baseline calculations. 
On Day 1 of Period 1, subjects will be randomized to 1 of 
12 treatment sequences. Each treatment sequence comprises 
4 treatment periods. 
On Day 1 of each period, subjects will receive single-dose SC 
injection of BL-8040 (therapeutic or supratherapeutic dose), 


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single-dose SC injection of BL-8040-matching placebo, or a single 
oral dose of moxifloxacin. Cardiodynamic readings, plasma PK 
samples, and blood PD samples will be collected at different time 
points prior to dosing and up to 24 hours postdose in each period, as 
appropriate. 
There will be a washout period of 5-7 days between dosing in each 
period. 
All subjects who received at least one dose of any study drug 
(including subjects who terminate the study early) will return to the 
clinical research unit (CRU) 7 ± 2 days after the last dose for 
follow-up procedures, and to determine if any adverse event (AE) has 
occurred since the last study visit. 
Number of 
Subjects: 
Approximately 40 healthy, adult male and female subjects will be 
enrolled to ensure at least 26 subjects complete the study. Every 
attempt will be made to enroll no less than 30% of either gender. 
Dosage, Dosage 
Form, Route, and 
Dose Regimen: 
Subjects will receive each one of the following treatments in a 
pre-defined order according to the sequence scheme determined at 
randomization. The sequences to be used in the randomization are 
detailed in Table 4. 
Treatments are described as follows: 
Treatment A: 
(Therapeutic) 
1.25 mg/kg BL-8040 + BL-8040-matching 
placebo administered via SC injection 
Treatment B: 
(Supratherapeutic) 
2 mg/kg BL-8040 administered via SC 
injection 
Treatment C: 
(Placebo Control) 
BL-8040-matching placebo administered 
via SC injection 
Treatment D: 
(Positive Control) 
400 mg moxifloxacin (1 x 400 mg tablet) 
administered orally 
For each subject, an appropriate volume of BL-8040-matching 
placebo will be used in Treatments A and C such that the total 
volume administered for each of Treatments A and C will be the 
same as the total volume injected in Treatment B. 
All study drugs will be administered on Day 1 following an overnight 
fast. Moxifloxacin will be administered with approximately 240 mL 
of water. Hour 0 will be set as the start of dosing. 


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Key Assessments: 
Cardiodynamics: 
The following ECG parameters will be measured and calculated: HR, 
RR, PR, QRS, QT, QTcI, Fridericia corrected QTc (QTcF), and ECG 
waveform morphologies. 
The primary analysis will be based on concentration-QTc modeling 
of the relationship between plasma concentrations of BL-8040 and 
change-from-baseline QTcI (ΔQTcI) with the intent to exclude an 
effect of placebo-corrected ΔQTcI (2-sided 90% upper confidence 
bound of ΔΔQTcI) > 10 msec at clinically relevant plasma levels. 
The relationship between BL-8040 plasma concentration and ΔQTcF 
will be explored. In addition, the effects of BL-8040 on the 
change-from baseline placebo-corrected QTcI, QTcF, HR, PR, and 
QRS (∆∆QTcI, ∆∆QTcF, ∆ΔHR, ∆ΔPR, and ∆ΔQRS) will be 
evaluated at each postdose time point (“by time point” analysis). An 
analysis of categorical outliers will be performed for changes in 
QTcI, QTcF, HR, PR, and QRS. Morphologic analyses will be 
performed on the ECG waveforms. Assay sensitivity will be 
evaluated by concentration-QTc analysis of the effect on ∆ΔQTcI of 
moxifloxacin using a similar model as for the primary analysis. 
Assay sensitivity will be deemed as met if the slope of the 
concentration-QTc relationship/ΔQTcI is statistically significant at 
10% level of significance in a 2-sided test and the predicted QT 
effect (i.e., the lower bound of the 2-sided 90% confidence interval 
[CI] of ΔΔQTcI) is above 5 msec at the observed geometric mean 
Cmax of 400 mg moxifloxacin. 
Pharmacokinetics: 
The following PK parameters will be calculated for BL-8040 and 
moxifloxacin in plasma, as appropriate: AUC0-t, AUC0-inf, 
AUC%extrap, Cmax, Tmax, Kel, t½, CL/F, and Vz/F. 
PK parameters will be summarized by treatment using descriptive 
statistics. 
Safety: 
Safety will be monitored through AEs, 12-lead safety ECGs, vital 
sign measurements, clinical laboratory tests, and physical 
examination. AEs will be tabulated and descriptive summary 
statistics for the 12-lead safety ECGs, vital signs, and clinical 
laboratory tests will be computed and provided, as appropriate. 
 








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a 
For details on Procedures, refer to Section 13. 
b 
Within 28 days prior to check-in (Day -2 in Period 1). 
c 
There will be a washout period of 5-7 days between dosing in each period. Each subject will participate for a total for 4 periods. 
d 
All subjects who received at least one dose of any study drug (including subjects who terminate the study early) will return to the CRU 7 ± 2 days after the 
last dose for follow-up procedures, and to determine if any AE has occurred since the last study visit. 
e 
Subjects will be admitted to the CRU on Day -2 in Period 1, at the time indicated by the CRU, and will remain confined until completion of study procedures 
on Day 2 of Period 4. Procedures scheduled on Day -2 will only be performed in Period 1. 
f 
The 16-hour postdose on Day 1 will be either on Day 1 or Day 2, depending on the time of dosing on Day 2. 
g 
Symptom-driven physical examination may be performed at additional times, at the PI or designee’s discretion. 
h 
To be performed at the end of each period or prior to early termination from the study. 
i 
To be performed only in Periods 2, 3, and 4. 
j 
Samples for serum chemistry will be obtained after a fast of at least 8 hours, however, in case of early discontinuation or rechecks, subjects may not have 
fasted for 8 hours prior to the serum chemistry sample is taken. 
k 
 To be performed prior to study drug dosing, but after the last baseline cardiodynamic ECG reading. 
l 
In Period 1 only. Subjects will be randomized to 1 of 12 treatment sequences (Table 4). 
m Premedication will be administered to all subjects as described in Section 12.1, prior to the first baseline cardiodynamic ECG reading. 
n 
Holter monitors will be used to collect continuous cardiodynamic ECG samples on Day -1 of Period 1 and Day 1 of each period. On Day 1 of each period, 
ECG recordings will be extracted from the Holter monitor data within a 5-minute time window prior to the PK blood sample collection. Subjects must rest 
quietly in the supine position for at least 10 minutes prior to the extraction and throughout the duration of the extraction. There should be minimal movement 
and minimal exposure to noise and other environmental stimuli (e.g., TV, loud radio, interactions with other subjects). When cardiodynamic ECG 
extractions coincide with 12-lead safety ECGs, vital signs assessment, and blood draws, procedures should be carried out in this order: 12-lead safety ECG, 
cardiodynamic ECG extraction, and blood sample for PK assessments as close to the exact time point as possible. Vital signs may be performed either before 
or after blood sample collection. 
o 
To be performed in Period 1 only. Holter monitors will be used to collect a continuous 12-lead cardiodynamic ECG recording for approximately 24 hours on 
Day -1. 
 
 
Abbreviations: AE = Adverse event(s), BP = Blood pressure, C-I = Check-in, CBC = Complete blood count, Chem = Chemistry, Coag = Coagulation, 
CRU = Clinical research unit, ECG = Electrocardiogram, FSH = Follicle-stimulating hormone, FU = Follow-up, Hem = Hematology, HIV = Human 
immunodeficiency virus, HR = Heart rate, PI = Principal Investigator, 
, T = Temperature, UA = Urinalysis. 


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7 
ABBREVIATIONS 
14C 
Carbon-14 (radiocarbon) 
ADME 
Absorption, distribution, metabolism, and excretion 
AE 
Adverse event 
AML 
Acute myeloid leukemia 
AUC 
Area under the concentration-time curve 
AUC%extrap 
Percent of AUC0-inf extrapolated  
AUC0-t 
Area under the concentration-time curve, from time 0 to the last observed 
non-zero concentration (t) 
AUC0-inf 
Area under the concentration-time curve, from time 0 extrapolated to 
infinity 
AV 
Atrioventricular 
BMI 
Body mass index 
bpm 
Beats per minute 
°C 
Degrees Celsius 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL/F 
Apparent total plasma clearance after extravascular administration 
cm 
Centimeter 
Cmax 
Maximum observed concentration  
CNS 
Central nervous system 
CRF 
Case report form 
CRU 
Clinical research unit 
CSR 
Clinical study report 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
∆ 
Change-from-baseline 
∆∆ 
Placebo-corrected change-from-baseline 
DDI 
Drug-drug interaction 
DNA 
Deoxyribonucleic acid 
DRF 
Dose range finding 


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ECG 
Electrocardiogram 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
g 
Gram 
G-CSF 
Granulocyte-colony stimulating factor 
GCP 
Good Clinical Practice 
h 
Hour 
HBsAg 
Hepatitis B surface antigen 
HED 
Human equivalent dose 
hERG 
Human ether-a-go-go related gene 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HLM 
Human liver microsome(s) 
HR 
Heart rate 
HSC 
Hematopoietic stem cell 
IB 
Investigator’s brochure 
IC50 
Half maximal inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IKr 
Rapid delayed rectifier 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional review board 
IV 
Intravenous 
Kel 
Apparent terminal elimination rate constant 
kg 
Kilogram 
LS 
Least-squares 
µg 
Microgram 
µL 
Microliter 
µM 
Micromolar 
m2 
Meters squared 


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MATE 
Multidrug and toxin extrusion protein 
MedDRA® 
Medical Dictionary for Regulatory Activities® 
mg 
Milligram 
min 
Minute(s) 
mIU 
Milli International Units 
mL 
Milliliter 
mmHg 
Millimeter of mercury 
msec 
Millisecond 
n 
Sample size 
ng 
Nanogram 
nM 
Nanomolar 
No. 
Number 
NOAEL 
No observed adverse effect level 
NOEL 
No observed effect level 
OAT 
Organic anion transporter 
OATP 
Organic anion-transporting polypeptide 
OCT 
Organic cation transporter 
oz 
Ounce 
PD 
Pharmacodynamic(s) 
PEPT 
Peptide transporter 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PR 
Interval from the onset of the P wave to the start of the QRS complex 
QA 
Quality Assurance 
QRS 
QRS complex; interval including the Q, R, and S waves 
QT 
Interval between the Q and T waves on the electrocardiogram tracing 
QTc 
Corrected value of the interval between the Q and T waves on the 
electrocardiogram tracing 
QTcF 
Fridericia corrected QT interval 
QTcI 
Optimized heart rate-corrected QT interval 
RA 
Radioactivity 
RNA 
Ribonucleic acid 
RO 
Receptor occupancy 


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RR 
Interval between two successive R waves on the electrocardiogram tracing 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous or subcutaneous(ly) 
SD 
Standard deviation 
SE 
Standard error 
SOP 
Standard operating procedure 
SSS 
Sum of squared slopes 
t½ 
Apparent terminal elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to reach maximum observed concentration 
TQT 
Thorough-QT 
US 
United States 
USA 
United States of America 
Vz/F 
Apparent volume of distribution during the terminal elimination phase after 
extravascular administration 
WBC 
White blood cell 
WHO 
World Health Organization 
 


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8 
INTRODUCTION 
8.1 
BL-8040 (Motixafortide) 
BL-8040 (INN: motixafortide, formerly known as 4F-benzoyl-TN14003 or BKT140 and 
developed by Biokine Therapeutics Ltd.) is a novel selective inhibitor of the CXCR4 
chemokine receptor. BL-8040 is a synthetic peptide that binds and inhibits the CXCR4 
chemokine receptor with high affinity (IC50 1-10 nM). BL-8040 has been shown in-vitro and 
in-vivo to be a specific antagonist of the CXCR4 receptor and to have a slow dissociation 
rate from the receptor. In in-vivo animal studies, as well as in clinical studies, BL-8040 has 
demonstrated accelerated mobilization of adult white blood cells (WBCs [neutrophils, 
monocytes, and lymphocytes]), normal hematopoietic stem-cells, and leukemic blasts (in 
study performed on acute myeloid leukemia [AML] patients) from the bone marrow to the 
peripheral blood. In-vitro and in-vivo nonclinical studies have shown that in addition to its 
activity as a mobilizer of hematopoietic cells, BL-8040 exhibits a CXCR4-dependent 
preferential anti-tumor effect against malignant cells. In-vivo nonclinical studies have also 
shown that multiple doses of BL-8040 have led to a marked increase in the number of 
hematopoietic progenitor cells and HSCs in the bone marrow and peripheral blood of mice. 
In addition, BL-8040 promoted increased megakaryopoiesis in the bone marrow, leading to 
increased platelet production with a prolonged effect in-vivo. 
More complete details and references for the nonclinical and clinical background sections of 
this report may be found in the BL-8040 Investigator’s Brochure (IB) (IB v8.0, 2020). 
BioLineRx is developing BL-8040 for several indications, including the mobilization of 
HSCs for autologous and/or allogeneic transplantations in subjects undergoing peripheral 
blood stem cell transplantation, the treatment of patients with hematological malignancies or 
pre-malignant conditions, the treatment of patients with solid tumors, and the treatment of 
bone marrow failure diseases. 
8.1.1 Nonclinical Pharmacology and Pharmacokinetics 
BL-8040 is a synthetic cyclic peptide with molecular formula C97H144N33O19S2F and average 
molecular weight of 2160 Daltons. The antagonistic effects of BL-8040 on the CXCR4 
chemokine receptor were characterized in in-vitro and/or in-vivo systems. BL-8040 inhibited 
the binding of CXCL12 to CXCR4 and selectively inhibited CXCL12-stimulated cellular 
activities, such as calcium flux, chemotaxis, binding and hematopoietic. BL-8040 is a potent 
inhibitor of the CXCR4 chemokine receptor, and induces rapid (0.5-2 hour), dose-dependent, 
and transient mobilization of WBCs, including monocytes, B cells, T cells, progenitors and 
HSCs in mice treated with BL-8040 as a single agent. The effect was seen in mice at a dose 
range of 2.5-10 mg/kg, equivalent to 0.2-0.83 mg/kg, respectively, in humans. 
The nonclinical absorption, distribution, metabolism, and excretion (ADME) of BL-8040 has 
been evaluated in several in-vitro and in-vivo studies. The studies included evaluation of 
BL-8040 stability in plasma and whole blood, metabolic stability in liver microsomes, 
drug-drug interaction (DDI) studies (cytochrome P450 [CYPs] and transporters), and protein 
binding studies. PK/mass balance and metabolite radio-profiling and identification studies 


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with [14C]-Tyr BL-8040 and [14C]-Nal-BL-8040 were conducted in dogs and rats. Tissue 
distribution studies were conducted in rats with [14C]-Tyr BL-8040 and [14C]-Nal-BL-8040. 
Additionally, identification of the metabolic products in the stability assays was performed 
and the metabolic profiles of toxicology models (rats and dogs) and humans (in-vitro) were 
compared. 
BL-8040 exhibited very high binding to human plasma proteins (99.2%) and high binding to 
the proteins in rat and dog plasma (94.9% and 96.9%, respectively). Absorption studies of 
BL-8040 were performed in rats and dogs following SC (the clinical administration route) 
and/or intravenous (IV) administration (to maximize exposure). PK parameters calculated for 
BL-8040 following increasing doses injected IV or SC demonstrated a linear kinetic profile. 
Absorption following SC doses of BL-8040 in dogs was rapid, the elimination half-life (t½) 
ranged from ~0.36-5.8 hours across several studies. The time to maximum plasma 
concentrations (Tmax) was generally 1-2 hours with no obvious differences between sex and 
doses. Plasma exposures were higher after repeated administrations compared to single-dose 
administration. Accumulation was modest, with approximately 1.5 fold higher Cmax and 
area under the curve (AUC) after multi-day (28-day) dosing. 
Investigation of the ADME properties of BL-8040, and specifically the disposition of 
unnatural amino acids of BL-8040 was conducted. The initial ADME studies in rats and dogs 
using [14C]-Tyr BL-8040 resulted in low recovery (overall radioactivity [RA]) excreted in 
urine and feces was 9% and 12% of the administered RA dose in rat and dog, respectively) of 
excreted RA. Approximately 21% of administered RA was accounted for expired air in rats. 
This was probably related to the labeling position at the natural amino acid and likely reflect 
the rapid digestion of [14C]-Tyr-labelled BL-8040 to the constituent amino acids and 
incorporation of the radiolabeled natural amino acid into downstream de novo synthesis of 
other peptides/proteins. In these studies, plasma metabolic profiles observed in rats and dogs 
were qualitatively and quantitatively similar and represented two major metabolic pathways: 
catabolism to individual amino acids and catabolism in parallel with mono- and 
polydeimination (citrullination) of Arginine residues. 
None of the circulating individual metabolites exceeded 1.5% of total plasma RA exposure 
with the exception of labeled Tyr (free amino acid) (66.1% [rat]; 22.1% [dog]) which was 
cleared quickly through identified pathways. Due to the low recovery of excreted 
radioactivity obtained with the Tyr-labelled compound the information collected from these 
studies supported mainly the metabolite profile and identification at the early time points 
after drug administration, and these studies were therefore complemented with additional 
studies using 14C-labeled BL-8040 with 14C label in the naphthalene ring at the unnatural 
amino acid Nal. 
Following a single SC administration of radiolabeled [14C]-Nal-BL-8040 the recovery of RA 
was almost complete in rats and dogs with 97% and 96% of RA excreted in rats and dogs, 
respectively. Approximately 80% of RA was excreted with urine with no parent drug 
detected in both species within 96 hours. There was no detectable RA in expired air. 
In both rat and dog, no major metabolite (or parent drug) in urine exceeded 30% of total 
clearance. The total amount of [14C]-Nal-BL-8040-related material excreted in feces as a 


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percentage of the administered dose was approximately 12.41% and 3.92% in rats and dogs, 
respectively up to 168 hours postdose. There was no detectable parent drug in feces of either 
species, and thus biliary excretion of parent drug is assumed to be minimal. Biliary excretion 
also appears to be only a very minor elimination pathway for BL-8040 metabolites, with 
cumulative excretion of individual metabolites in feces never exceeding 3.21% and 1.08% of 
the dose in rat and dog in respectively. 
Plasma metabolic profiles observed in rats and dogs following administration of 
[14C]-Nal-BL-8040 were similar with formation of free Nal (58.6% [rat]; 33.5% [dog]) and 
its further metabolism via identified metabolic pathways. One of these Nal-derivative 
metabolites circulating in the plasma, 2-naphthalene-acetic acid, was represented in different 
levels in rat and dog (7.5% and 55.5%, respectively) and 2 Nal-related metabolites in dog 
urine were >20% of the dose but were not major species in rat urine. 
Together these findings support the position that hepatic or renal impairment will not affect 
the PK profile of BL-8040. Overall the ADME studies show that BL-8040 is catabolized via 
hydrolysis and/or disulfide bond cleavage to form smaller peptides, and single amino acids, 
as expected. 
Following a single SC administration of radiolabeled [14C]-Nal-BL-8040 tissue distribution 
was rapid and widespread in rats with detectable concentrations measured in all tested tissues 
by 1 hour postdose and, reaching maximum concentrations between 4 and 8 hours postdose. 
Most tissues were below quantification limit at 840 hours postdose. The injection site, aorta, 
urinary bladder wall, kidney, pancreas and ocular system contained highest [14C]-Nal-
BL-8040-derived distribution of radioactivity at moderate and/or sustained levels 
(tissue:blood AUC0-t ratios of 1.11 to 42.90). BL-8040 show negligible penetration through 
the blood-brain barrier.  
In-vitro stability study in whole blood and plasma from rat, dog, and human whole blood and 
plasma suggested that BL-8040 is stable in all three species. Five metabolites (degradation 
products of BL-8040 ) were identified following 2 hours of incubation in liver microsomes. 
The metabolic profiles, as tested in in-vitro using liver microsomes of rat, dog and human, 
are similar across species, with the exception of 3 minor unique human catabolites that were 
observed at low levels in this system. However, the liver microsome findings are of less 
relevance since 1. the main excretion pathway of BL-8040 catabolites is via the kidneys, 
2. the catabolism is non-NADPH dependent and 3. drug permeability to the liver is low. 
Therefore, metabolites formed in blood/plasma ex-vivo better represent the in-vivo 
elimination profile. Moreover, the inhibitory activity of BL-8040 and two of its minimally 
proteolyzed human catabolites was tested in vitro using the CXCL12-CXCR4 chemotaxis 
assay. These catabolites with one or two amino acids cleaved from the C-terminus of 
BL-8040, exhibited poor to no inhibition of CXCL12-CXCR4 chemotaxis suggesting that 
further truncated versions of BL-8040 are not expected to exhibit activity. 
Evaluation of in-vitro metabolism of BL-8040 in rat, dog, and human liver microsomes 
(HLM) demonstrated that BL-8040 was moderately metabolized, with 51.9-70.8% remaining 
following incubation. BL-8040 was found to be a low clearance compound with intrinsic 
clearance rates from 2.9-6.0 μL/min/mg protein. The disappearance t½ values of BL-8040 


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ranged from 1.93-3.98 hours. Presence of Nicotinamide Adenine Dinucleotide Phosphate 
(NADPH) in the incubation samples containing human microsomes had a minor effect on the 
t½ values of BL-8040, indicating that the majority of the biotransformation was made 
through NADPH-independent enzymes with a minimal contribution of NADPH-dependent 
enzymes.  
Sixteen metabolites were identified following BL-8040 incubation with rat, dog, and HLM. 
All were hydrolysis and/or disulfide bond cleavage products of BL-8040 and no other 
biotransformations were observed. All major metabolites found in human were also 
identified in animal species. Given that BL-8040 is a peptide (molecular 
weight = 2160 g/mol) unlikely to reach significant intracellular concentrations in intact 
hepatocytes (cells that more closely resemble in-vivo conditions compared to liver 
microsomes), the in-vivo relevance of at least some of the biotransformation products 
observed following microsomal incubation should be viewed cautiously. 
Direct inhibitory effects of BL-8040 on all tested CYPs were observed in pooled HLM with 
apparent IC50 values ranging from 9.3 to 32.4 μM. The inhibitory effects of BL-8040 
remained similar after a 30-minute pre-incubation with apparent IC50 values ranging from 
10.0 to 47.1 μM, indicating that inhibition was not time-dependent. Contrary to HLM, 
BL-8040 did not cause > 25% inhibition of the activities of CYP isozymes (CYP2B6, 2C8, 
and 3A4) in human hepatocytes at concentrations as high as 50 μM despite potent inhibition 
of BL-8040 on these three enzymes (IC50 of 9.3-15.3 μM). Inhibition in hepatocytes was 
lower than microsomes (i.e., less potent) likely due to decreased uptake of BL-8040 into 
cells. Taking into account plasma protein binding, based on the fact that the expected human 
Cmax total is < 2 μM and only 1% of BL-8040 is found in the unbound fraction, the in-vitro 
human hepatocyte results predicts that BL-8040 exhibits a low potential for in-vivo CYP 
inhibition. 
BL-8040 at concentrations of up to 10 μM showed no induction potential for CYP1A2, 2B6, 
and 3A4, based on assays performed in cryopreserved plateable human hepatocytes.  
In the transporters assay, BL-8040 is not an inhibitor of organic anion-transporting 
polypeptide (OATP) 1B, organic anion transporter (OAT) 1, peptide transporter (PEPT) 1, 
and PEPT2. Inhibitions were < 25% for OATP1B3, OAT3, bile salt export pump, multi-drug 
resistance-1, and breast cancer resistance protein (14.6% to 22.8%) at concentrations up to 
10 μM. BL-8040 inhibited multidrug and toxin extrusion protein (MATE) 1, MATE2-K, 
organic cation transporter (OCT)1, and OCT2 with apparent IC50 values of 2.7, 26.9, 20.1 
and 5.1 μM, respectively. Considering BL-8040’s protein binding profile in human plasma, 
the Cmax unbound (Cmax total x 1%) / IC50 of BL-8040 is less than the threshold (i.e., 0.1 
for Food and Drug Administration [FDA] and 0.02 for European Medicines Agency [EMA]) 
considered to be indicative of potential inhibition in-vivo. The clinical inhibition potential for 
respective transporters is, therefore, considered to be remote based on FDA and EMA DDI 
guidance, respectively. In summary, the in-vitro DDI results suggest a low potential for DDIs 
with BL-8040. 


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8.1.2 Nonclinical Toxicology 
The nonclinical toxicology program with BL-8040 consisted of a series of acute (single-dose) 
and multiple-dose (up to 28 days) toxicology studies, which were conducted in 
Sprague-Dawley rats and beagle dogs. SC and IV dose range-finding studies were 
subsequently followed by multiple-dose (up to 28 days) studies in each species. All definitive 
studies used the SC route, which is the clinical route of administration, appropriate dosing 
schedule and duration to adequately address the safety concerns for the indicated patient 
population and the intended clinical schedule (up to daily administrations for 4 weeks). In 
some studies, the IV route was used in order to maximize exposure. In the 14-day toxicology 
study, the highest tested dose in rats was 15 mg/kg and 9 mg/kg in the 7 days toxicology 
study in dogs. The definitive 28-day studies involved the daily administration of BL-8040 at 
doses of up to 6 mg/kg in rats and up to 3 mg/kg in dogs. These definitive multiple-dose 
studies included comprehensive clinical evaluations, systemic exposure evaluations 
(toxicokinetic) and the microscopic assessment of a complete panel of tissues. The 
multiple-dose dog studies included ECG measurements. Systemic exposure comparison 
between the non-clinical safety studies with the highest systemic exposures in humans 
suggested that the animal exposure levels of the high dose in the acute and repeat dose up to 
7-day toxicology studies supported the human doses in the initial studies in patients (Study 
BKTSC001 and 201602037) and in healthy adults (BL-8040.02). However, in the subsequent 
repeat-dose toxicity studies (28 days), the exposure levels decreased and the systemic 
exposure comparison between the dose levels of no observed adverse effect level (NOAEL); 
3 mg/kg in rat and 1 mg/kg in dog, to the highest systemic exposures reached in humans’ 
clinical dose (single SC dose up to 1.25 mg/kg) indicates that there are no safety margins. 
Exposures at doses determined as no observed effect level (NOEL) in safety pharmacology 
studies were slightly higher (central nervous system [CNS] and respiratory evaluations) or 
similar (cardiovascular effects mentioned above) to those observed in the initial clinical 
testing. 
The safety pharmacology studies and general toxicology studies in rats and dogs identified 
the injection site, as well as the cardiovascular, respiratory and CNS systems as the potential 
target organs/tissues. The common findings included: transient anaphylactic-type reaction, 
CNS related clinical signs (ataxia and decreased activity in rats during first week of 
treatment/head twitching and decreased activity in dogs), increase in WBC counts (total and 
differential which correlated with the pharmacological activity of BL-8040), injection site 
lesions (SC hemorrhage and inflammation), respiratory effects (decrease in inspiration time, 
together with a marked increase in minute and tidal volumes) and cardiovascular effects (a 
dose-dependent short-lasting hypotensive effect followed by a dose dependent long-lasting 
hypertensive effect, combined with a dose dependent tachycardia seen in dogs). No 
histopathological adverse changes were identified in the pivotal toxicity studies excluding the 
injection sites. Similar local clinical symptoms were observed in rats and dogs immediately 
after first and subsequent BL-8040 administrations and consisted of transient anaphylactic-
type reaction (edema and/or erythema of the face, ears, muzzle, and/or paws observed 
immediately). In dogs, the reactions were noticed from a few minutes up to approximately 
2 hours following SC injection. Tolerability was demonstrated with repeated administrations 
over time as the magnitude of the systemic reactions was less pronounced with time and not 


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aggravated with increasing dose. Lesions at the injection sites (SC hemorrhage and 
inflammation) were associated with the high concentration formulation and/or volume of 
injection and/or repeated needle penetrations. In addition, the transient mild-to-moderate 
local AEs may be related to BL-8040 secondary PD action which leads to the localized 
activation of mast cells. 
8.1.3 Nonclinical Safety Pharmacology 
8.1.3.1 
Cardiovascular System Assessment 
The cardiovascular effects of BL-8040 were evaluated on arterial blood pressure, HR, and 
ECG after single SC administration of 0.23, 2.3 and 6.8 mg/kg to beagle dogs (3/sex). 
BL-8040 was tested in a crossover design after allowing a minimum washout period of 
48 hours between treatments. Telemetric measurements started at least 3 hours before 
administration and were continued for 24 hours following dosing. Part 2 of the study 
included complementary investigations (6-lead ECG evaluation and animals’ observation) 
was conducted following single SC administration of 6.8 mg/kg. 
BL-8040 administered by the SC route to conscious telemetered dogs induced a 
dose-dependent hypotensive effect followed by a dose-dependent hypertensive effect at doses 
of 2.3 and 6.8 mg/kg (human equivalent dose [HED] of 1.28 mg/kg and 3.8 mg/kg, in 
respectively). BL-8040-induced hypotension was short lasting, approximately 30 minutes, 
whereas BL-8040-induced hypertension was more long-lasting, i.e., 10-12 hours at the dose 
of 6.8 mg/kg (3 folds higher than the clinical dose of 1.25 mg/kg). It is worthy of note that, 
arterial blood pressure changes were moderate in average at both doses of 2.3 and 6.8 mg/kg 
and were characterized by a high inter-individual variability. 
These effects were combined with a dose-dependent tachycardia with a maximum effect 
observed from 30 minutes to 1 hour postdose, most likely reflex mediated. Thereafter, the 
duration of the tachycardia was well correlated with the hypertensive effect. The short lasting 
hypotension and reflex mediated tachycardia were associated with a high inter-individual 
variability, and were followed by a long term tachycardia and hypertension, that could be 
related to systemic and local reactions observed after dosing with BL-8040 at 2.3 and 
6.8 mg/kg. 
A shortening in PR and PQ intervals as well as in the QRS complex was found especially at 
the peak of tachycardia, suggesting that these electrocardiographic changes are likely a 
consequence of the tachycardic properties of BL-8040. 
QT interval was also shortened in a dose-dependent manner at doses of 2.3 and 6.8 mg/kg. 
The QT interval shortening was well correlated with the tachycardic properties of BL-8040. 
Analysis of QTc interval changes using the probabilistic method or the QT shift method 
suggests that the QT interval shortening is related to a decrease in ventricular repolarization 
duration rather than a consequence of tachycardic properties of BL-8040. 
No change in T wave morphology was observed in any of the groups. No arrhythmias 
attributable to BL-8040 administration were observed. No ECG changes (6 leads) attributable 
to the administration of BL-8040 at 6.8 mg/kg were observed. 


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Because few changes in HR only were found at the dose of 0.23 mg/kg, the NOAEL of 
BL-8040 on cardiovascular parameters in conscious dogs was considered at 0.23 mg/kg, 
when administered by the SC route. The HED was calculated to be 0.128 mg/kg. 
In follow up evaluations the effect of BL-8040 on ECG parameters were assessed in the dose 
range finding (DRF) 7-day and in the 28-day repeat-dose studies in beagle dogs. In the DRF 
7-day study, blood pressure and ECG measurements were performed at pre-treatment, and at 
0.5 and 24 hours post treatment following BL-8040 treatment as single SC dose of up to 
27 mg/kg (HED of 15 mg/kg) and 7 days repeat dose of up to 9 mg/kg (HED of 5 mg/kg). 
There were no clear effects of BL-8040 on the ECG parameters, blood pressure and HR 
values evaluated, as compared to pre-treatment data. Occasional increases in the HR at 
30 minutes postdose or decrease in the systolic blood pressure were observed but due to low 
number of animals (1/sex) and inconsistencies between genders at various dose levels, the 
variations observed were attributed to a high inter-individual variability and could not be 
concluded. No significant changes were noted on the QT interval at any of the dose levels 
tested. In the 28 days, dogs were treated with BL-8040 dose levels of 0.3, 1, and 3 mg/kg 
(3/sex-main; 2/sex-recovery). The electrocardiography evaluations were performed on 
pre-treatment, Day 27 and Day 41 (recovery) prior to BL-8040 administration. No 
BL-8040-related differences were observed following repeated BL-8040 treatments up to 
3 mg/kg (HED of 1.6 mg/kg) or recovery periods in the electrocardiography parameters 
evaluated as compare to the control group. In addition, no histopathological adverse findings 
were identified in the cardiovascular system tissues. 
8.1.4 Clinical Data 
As of April 2021, three clinical trials were completed, one was closed due to lack of 
recruitment, one is in the stages of closure, seven clinical trials are ongoing, and three are in 
long-term follow-up. The trials are conducted either as BioLineRx sponsored studies, 
Sponsor-Investigator trials, or as studies sponsored by collaborative partners of BioLineRx. 
Details are provided below. 
Completed studies: 
• Study BKTSC001 was a non-randomized, open-label, single administration, 
dose-escalation study, where BL-8040 was administered to patients with newly 
diagnosed multiple myeloma who were undergoing treatment with 
chemo-mobilization and granulocyte-colony stimulating factor (G-CSF). 
• Study BL-8040.02 was a Phase I clinical study in healthy subjects evaluating 
BL-8040 as a single agent for stem cell mobilization. 
• Study BL-8040.01 is a Phase IIa clinical trial for the treatment of adult 
relapsed/refractory AML patients with a combination of BL-8040 and cytarabine 
(Ara-C). 


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Closed studies: 
• Study BL-8040.AML.202, ‘BATTLE’, was a Phase Ib/II study evaluating safety, 
tolerability and efficacy of the BL-8040 and atezolizumab combination for 
maintenance treatment in patients with AML. One subject was treated. In April 2020, 
the study was terminated due to lack of recruitment. 
Studies in closure stages: 
• Study BL-8040.06, a Phase Ib study evaluating the efficacy and safety of BL-8040 
followed by standard immunosuppressive therapy in adult subjects with aplastic 
anemia or hypoplastic myelodysplastic syndrome. 
Studies in long-term follow-up: 
• Study 201602037, an investigator-sponsored Phase II study evaluating the safety and 
efficacy of BL-8040 for the mobilization of donor HSC and allogenic transplantation 
in patients with advanced hematological malignancies. 
• Study 2016-0410, an investigator-initiated Phase IIb pilot study to assess the efficacy, 
safety and PD effects of pembrolizumab and BL-8040 in patients with metastatic 
pancreatic cancer. 
• Study WO39608, a Roche-sponsored study to evaluate the combination of 
atezolizumab and BL-8040 in patients with metastatic pancreatic cancer. 
Ongoing studies: 
• Study BL-8040.SCM.301, called “GENESIS”, is a Phase III study evaluating safety, 
tolerability and efficacy of combination treatment of BL-8040 and G-CSF as 
compared to placebo and G-CSF for the mobilization of HSCs for autologous 
transplantation in subjects with multiple myeloma. 
• Study BL-8040.PAC.201, “COMBAT”, a Phase II clinical trial assessing the safety 
and efficacy of the combination of BL-8040 and pembrolizumab for metastatic 
pancreatic cancer. 
• Investigator-sponsored study UKH062014, termed “BLAST”, a Phase II study 
conducted in Germany. This study is assessing the efficacy of BL-8040 as an add-on 
therapy to standard of care consolidation therapy in AML patients in first complete 
remission. The study is a double blind, randomized placebo-controlled study. 
• Investigator-sponsored study 201606146, a Phase IIa Study of BL-8040 in 
combination with nelarabine for relapsed or refractory T-cell acute lymphoblastic 
leukemia/lymphoblastic lymphoma. 
• Investigator-sponsored study Chemo4METPANC, a Phase II study with combination 
chemotherapy (gemcitabine and Nab-Paclitaxel), chemokine (C-X-C) motif receptor 


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4 inhibitor (BL-8040), and immune checkpoint blockade (cemiplimab) in metastatic 
treatment naïve pancreas adenocarcinoma. 
• Investigator-sponsored COVID study: A Phase Ib, open-label study designed to 
evaluate the safety of BL-8040 (a CXCR4 antagonist) in patients with Acute 
Respiratory Distress Syndrome secondary to COVID-19 and other respiratory viral 
infections. 
• Collaborative study YO39609, termed “Morpheus-Gastric Cancer”, a Phase Ib/II 
studies sponsored by Roche to evaluate immunotherapy-based treatment 
combinations in patients with locally advanced unresectable or metastatic gastric or 
gastroesophageal junction cancer. 
8.1.5 Pharmacokinetics in Humans 
Study BL-8040.02 was a healthy subject study conducted in two parts. In Part 1, subjects 
received two injections of BL-8040 (once daily on 2 consecutive days) of 0.5 mg/kg 
(Cohort 1), 0.75 mg/kg (Cohort 2), and 1 mg/kg (Cohort 3). Each cohort consisted of 
6 subjects receiving BL-8040 and 2 subjects receiving matching placebo, in a double-blinded 
manner. Based on the safety and PD data from Part 1, the single dose of 1 mg/kg was 
selected for Part 2 of the study. Part 2 used an open-label design in which each subject 
received a single BL-8040 injection of 1 mg/kg BL-8040, followed by a standard 
leukapheresis procedure starting approximately 4 hours after the BL-8040 injection. 
After SC administration of BL-8040 on Day 1, the appearance of the compound in plasma 
was rapid, with a median Tmax ranging between 0.25 and 0.5 hour. Thereafter, plasma 
concentrations declined mono-exponentially with a short t½ of approximately 1 hour. For 
that reason, plasma levels of BL-8040 were below the limit of detection in the majority of 
subjects by 8 hours and in all subjects at 23 hours after dosing. Increases in the dose of 
BL-8040 led to overall approximate proportional increases in plasma exposure, as measured 
by Cmax, AUC0-t, AUC0-24, and AUC0-inf. Dose-normalized Cmax and AUC0-24 and t½ 
values were comparable across the 3 dose groups suggesting dose proportionality across the 
0.5 to 1.0 mg/kg dose range. 
In Study 201602037, a single SC dose of 1 mg/kg or 1.25 mg/kg BL-8040 was administered 
to healthy donors. Hematopoietic cells were collected for transplantation in sibling recipients. 
The PK parameters of BL-8040 in the donors show rapid appearance in plasma and short t½. 
By 24 hours, plasma levels of BL-8040 were below the limit of quantitation in 18 of the 25 
subjects. 
Study BL-8040.01 was a Phase IIa, 2-part study to assess the safety and efficacy of BL-8040 
(0.5-2.0 mg/kg) in combination with high dose cytarabine (Ara-C) in patients with 
relapsed/refractory AML (r/rAML). Part 1 was a dose escalation phase (3+3 dosing) and 
Part 2 was a dose expansion phase. Subjects received SC injections over 2 days (one per day) 
as monotherapy followed by concurrent daily administration of BL-8040 with Ara-C 
standard salvage chemotherapy over 5 days. During the “combined period,” BL-8040 was 
administered 4 hours prior to chemotherapy. 


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A summary of PK parameters on Day 1 (Table 1) and Day 7 (Table 2) is provided. Mean 
predose BL-8040 concentrations are provided by day in Table 3. BL-8040 was rapidly 
absorbed after SC administration, reaching maximum concentrations between 0.25 to 1 hour 
after dosing on Day 1, and declining with a half-life of 1 to 3 hours on average. After 
repeated daily administration, the PK of BL-8040 on Day 7 were comparable to Day 1. 
BL-8040 did not accumulate to any significant extent after daily dosing and predose levels 
were consistent across 6 measurements. Increases in the dose of BL-8040 led to increases in 
systemic exposure. The PK characteristics of BL-8040 in r/r AML patients are similar to 
those observed in healthy subjects. 


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Table 1: Summary of Day 1 BL-8040 Pharmacokinetic Parameters after Subcutaneous Administration in Subjects with 
Relapsed/Refractory Acute Myeloid Leukemia (Study BL-8040.01) 
Dose (mg/kg) 
 
t½ 
(h) 
Tmax 
(h) 
Cmax  
(ng/mL) 
AUC0-t 
(h*ng/mL) 
AUC0-24 
(h*ng/mL) 
AUC-inf 
AUC0-t  
Cmax/D 
(kg*ng/mL/mg) 
AUC-inf/D 
(h*kg*ng/mL/mg) 
0.5 
n 
1 
3 
3 
3 
1 
1 
3 
1 
Mean 
1.23 
0.833 
380 
661 
671 
671 
760 
1340 
SD 
NR 
0.289 
33.6 
55.3 
NR 
NR 
67.2 
NR 
Min 
NR 
0.500 
348 
605 
NR 
NR 
696 
NR 
Median 
NR 
1.00 
377 
662 
NR 
NR 
754 
NR 
Max 
NR 
1.00 
415 
716 
NR 
NR 
830 
NR 
CV% 
NR 
34.6 
8.84 
8.36 
NR 
NR 
8.84 
NR 
0.75 
n 
3 
3 
3 
3 
3 
3 
3 
3 
Mean 
1.50 
0.417 
376 
792 
809 
810 
501 
1080 
SD 
0.484 
0.144 
155 
447 
439 
438 
207 
584 
Min 
1.06 
0.250 
200 
279 
305 
307 
267 
410 
Median 
1.41 
0.500 
434 
998 
1020 
1020 
579 
1350 
Max 
2.02 
0.500 
494 
1100 
1110 
1110 
659 
1480 
CV% 
32.4 
34.6 
41.3 
56.4 
54.2 
54.0 
41.3 
54.0 
1.0 
n 
5 
6 
6 
6 
5 
5 
6 
5 
Mean 
1.40 
0.792 
712 
1390 
1550 
1550 
712 
1550 
SD 
0.336 
0.332 
277 
541 
484 
484 
277 
484 
Min 
1.07 
0.250 
336 
707 
933 
933 
336 
933 
Median 
1.38 
1.00 
750 
1370 
1500 
1500 
750 
1500 
Max 
1.93 
1.00 
1010 
2080 
2130 
2130 
1010 
2130 
CV% 
24.0 
42.0 
38.9 
38.9 
31.2 
31.2 
38.9 
31.2 


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Dose (mg/kg) 
 
t½ 
(h) 
Tmax 
(h) 
Cmax  
(ng/mL) 
AUC0-t 
(h*ng/mL) 
AUC0-24 
(h*ng/mL) 
AUC-inf 
AUC0-t  
Cmax/D 
(kg*ng/mL/mg) 
AUC-inf/D 
(h*kg*ng/mL/mg) 
1.25 
n 
4 
4 
4 
4 
4 
4 
4 
4 
Mean 
2.06 
0.875 
1670 
3020 
3060 
3070 
1340 
2450 
SD 
1.92 
0.250 
522 
1340 
1340 
1350 
418 
1080 
Min 
0.660 
0.500 
1290 
1570 
1600 
1600 
1030 
1280 
Median 
1.34 
1.00 
1480 
2880 
2940 
2940 
1180 
2350 
Max 
4.89 
1.00 
2430 
4750 
4750 
4790 
1940 
3830 
CV% 
93.3 
28.6 
31.3 
44.4 
43.7 
44.2 
31.3 
44.2 
1.5 
n 
18 
19 
19 
19 
18 
18 
19 
18 
Mean 
2.11 
0.618 
1940 
3650 
3840 
3860 
1290 
2570 
SD 
1.57 
0.281 
803 
1640 
1520 
1530 
535 
1020 
Min 
0.525 
0.250 
533 
571 
575 
575 
355 
384 
Median 
1.34 
0.500 
1910 
3580 
3650 
3670 
1270 
2450 
Max 
5.18 
1.00 
3420 
6670 
6700 
6700 
2280 
4470 
CV% 
74.1 
45.4 
41.4 
44.9 
39.6 
39.6 
41.4 
39.6 
2.0 
n 
3 
3 
3 
3 
3 
3 
3 
3 
Mean 
2.67 
1.00 
4020 
8340 
8370 
8390 
2010 
4200 
SD 
1.27 
0.00 
1510 
2290 
2260 
2260 
753 
1130 
Min 
1.29 
1.00 
2630 
6520 
6610 
6610 
1320 
3300 
Median 
2.93 
1.00 
3810 
7590 
7590 
7630 
1910 
3810 
Max 
3.79 
1.00 
5620 
10900 
10900 
10900 
2810 
5470 
CV% 
47.7 
0.00 
37.5 
27.5 
27.0 
27.0 
37.5 
27.0 
Note: NR = not reported (n <3) 
 
 


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Table 2: Summary of Day 7 BL-8040 Pharmacokinetic Parameters after Subcutaneous Administration in Subjects with 
Relapsed/Refractory Acute Myeloid Leukemia (Study BL-8040.01) 
Dose 
(mg/kg) 
 
t½ 
(h) 
Tmax 
(h) 
Cmax  
(ng/mL) 
AUC0-t 
(h*ng/mL) 
AUC0-24 
(h*ng/mL) 
Cmax/D 
(kg*ng/mL/mg) 
AUC-inf/D 
(h*kg*ng/mL/mg) 
0.5 
n 
3 
3 
3 
3 
3 
3 
3 
Mean 
1.52 
0.500 
546 
621 
634 
1090 
1270 
SD 
1.15 
0.00 
498 
373 
364 
996 
727 
Min 
0.556 
0.500 
65.3 
192 
216 
131 
432 
Median 
1.21 
0.500 
513 
806 
815 
1030 
1630 
Max 
2.79 
0.500 
1060 
866 
872 
2120 
1740 
CV% 
75.5 
0.00 
91.2 
60.1 
57.3 
91.2 
57.3 
0.75 
n 
1 
3 
3 
3 
1 
3 
1 
Mean 
1.29 
1.17 
365 
716 
1100 
487 
1460 
SD 
NR 
0.764 
205 
340 
NR 
273 
0.00 
Min 
NR 
0.500 
224 
403 
NR 
299 
1460 
Median 
NR 
1.00 
271 
666 
NR 
361 
1460 
Max 
NR 
2.00 
600 
1080 
NR 
800 
1460 
CV% 
NR 
65.5 
56.1 
47.6 
NR 
56.1 
0.00 
1.0 
n 
5 
6 
6 
6 
5 
6 
5 
Mean 
1.50 
0.708 
799 
1520 
1810 
799 
1810 
SD 
0.417 
0.332 
451 
795 
584 
451 
584 
Min 
1.15 
0.250 
167 
289 
1280 
167 
1280 
Median 
1.44 
0.750 
767 
1500 
1660 
767 
1660 
Max 
2.20 
1.00 
1540 
2700 
2740 
1540 
2740 
CV% 
27.9 
46.9 
56.4 
52.2 
32.3 
56.4 
32.3 


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Dose 
(mg/kg) 
 
t½ 
(h) 
Tmax 
(h) 
Cmax  
(ng/mL) 
AUC0-t 
(h*ng/mL) 
AUC0-24 
(h*ng/mL) 
Cmax/D 
(kg*ng/mL/mg) 
AUC-inf/D 
(h*kg*ng/mL/mg) 
1.25 
n 
4 
4 
4 
4 
4 
4 
4 
Mean 
4.71 
1.00 
1510 
3430 
3430 
1210 
2750 
SD 
1.27 
0.707 
480 
352 
352 
384 
282 
Min 
3.50 
0.500 
913 
3080 
3080 
730 
2470 
Median 
4.43 
0.750 
1590 
3380 
3380 
1270 
2710 
Max 
6.49 
2.00 
1960 
3880 
3880 
1570 
3100 
CV% 
27.0 
70.7 
31.7 
10.3 
10.3 
31.7 
10.3 
1.5 
n 
18 
19 
19 
19 
19 
19 
19 
Mean 
4.12 
0.671 
1400 
3420 
3440 
935 
2290 
SD 
1.64 
0.264 
706 
1850 
1840 
470 
1220 
Min 
1.24 
0.250 
472 
1040 
1090 
315 
728 
Median 
4.41 
0.500 
1360 
3020 
3250 
907 
2160 
Max 
6.72 
1.00 
2870 
6970 
6970 
1910 
4650 
CV% 
39.9 
39.4 
50.3 
54.0 
53.4 
50.3 
53.4 
2.0 
n 
3 
3 
3 
3 
3 
3 
3 
Mean 
5.48 
1.33 
2490 
8880 
8880 
1250 
4440 
SD 
3.03 
0.577 
1040 
2160 
2160 
520 
1080 
Min 
3.59 
1.00 
1330 
6610 
6610 
665 
3300 
Median 
3.88 
1.00 
2820 
9130 
9130 
1410 
4570 
Max 
8.98 
2.00 
3330 
10900 
10900 
1670 
5450 
CV% 
55.3 
43.3 
41.7 
24.3 
24.3 
41.7 
24.3 
Note: NR = not reported (n <3) 
 
 


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Table 3: Mean (SD) Predose BL-8040 Concentrations (ng/mL) by Day 
(Study BL-8040.01) 
Dose 
(mg/kg) 
Day 
2 
3 
4 
5 
7 
8 
0.5 
(n = 3) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.75 
(n = 3) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
1.0 
(n = 6) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
0.00 
(0.00) 
1.83 
(2.84) 
0.00 
(0.00) 
1.25 
(n = 4) 
1.56 
(3.11) 
1.94 
(3.35) 
9.02 
(NR) 
6.06 
(4.06) 
7.59 
(2.56) 
8.50 
(1.37) 
1.5 
(n = 19) 
1.67 
(2.85) 
3.65 
(3.91) 
3.01 
(3.97) 
6.84 
(8.30) 
8.35 
(7.37) 
7.00 
(5.15) 
2.0 
(n = 3) 
4.00 
(3.58) 
11.7 
(8.25) 
14.7 
(10.1) 
25.6 
(18.6) 
39.6 
(42.1) 
36.3 
(37.3) 
Note: NR = not reported (n <3). Day 8 is the 24-hour sample of Day 7 
Ara-C was administered on Days 3-7 
8.1.6 Safety Data in Human 
A total of 86 subjects were treated with BL-8040 in three completed BL-8040 clinical studies 
(BKTSC001, BL-8040.01, and BL-8040.02). Among the BL-8040-treated subjects, 
1238 AEs were reported, of which 787 events reported for 71 subjects (82.6%), and are 
considered related to BL-8040. 
In completed clinical studies with BL-8040 the following adverse reactions were observed 
with the highest frequencies (n=86 subjects): injection site reactions including: pain (59.3% 
of subjects), erythema (43%), oedema (29.1%), pruritus (23.3%), and rash (11.6%); and 
systemic reactions: flushing (32.6%), pruritus (not at the injection site; 32.6%), hot flushes 
(27.9%) and urticaria (23.3%). These two groups of reactions are well managed with 
pre-medication and/or post event treatment using antihistamines and/or steroids. Additional 
related AEs reported with relatively high frequency include nausea (20.9%), vomiting 
(12.8%), asthenia/fatigue (17.5%), paraesthesia (12.8%) and dizziness (1.6%). 
Additional uncommon treatment related adverse effects reported in ongoing clinical studies 
include hypokalemia, thrombocytopenia, hyperleukocytosis, elevated liver function tests, 
diarrhea, anaphylaxis, injection site skin necrosis (2 reported cases), abdominal pain, chest 
pain, bradycardia, and severe allergic reactions/anaphylaxis.  
The majority of the adverse reactions observed were transient and mild to moderate. 
Of note, leukocytosis is an expected PD effect of treatment with BL-8040. Although none of 
the BL-8040-treated subjects in the completed studies experienced leukostasis (BKTSC001 
in multiple myeloma patients, BL-8040 in healthy subjects and BL-8040.01 in adult r/r 
AML), leukostasis is a perceived potential safety issue based on the BL-8040 mechanism of 
action, and certain patient populations may be at higher risk. 


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Uncommon adverse reactions include one serious adverse reaction of acute leukocytosis 
accompanied by acute respiratory distress and encephalopathy and two serious adverse 
reactions of anaphylaxis. Other adverse reactions reported to date include paraesthesia, 
musculoskeletal pain, headache, constipation, diarrhea, abdominal pain, fatigue, nausea, 
vomiting, hypotension, increased liver transaminases, increased alkaline phosphatase, 
dyspnea and hypokalemia. 
8.1.7 Human Cardiac Safety 
Formal cardiac safety evaluation has not been performed to date for BL-8040. Few cardiac 
AEs and no serious ECG AEs have been reported to date. 
8.2 
Moxifloxacin 
Moxifloxacin hydrochloride is a synthetic C-8-methoxy-fluoroquinolone antimicrobial agent. 
It has different properties than other quinolone agents. While still active against gram 
negative pathogens, it is also highly active against gram-positive cocci, aerobic, anaerobic, 
intracellular bacteria and “atypical” organisms such as Mycoplasma and Chlamydia. Hence, 
it is effective for the treatment of respiratory tract infections, including acute exacerbations of 
chronic bronchitis, community-acquired pneumonia, and acute bacterial sinusitis. It is also 
indicated for the treatment of complicated and uncomplicated skin and skin structure 
infections, and complicated intra-abdominal infections. The recommended oral dose is 
400 mg once daily for 5 - 21 days, depending on the specific infection (Avelox 2019). 
Moxifloxacin is a reversible blocker of the potassium current of the cardiac rapid delayed 
rectifier (IKr) channel and causes a mean increase of the QTc interval of 10–14 msec 
between 2 and 4 hours after a single oral dose of 400 mg (Taubel et al, 2014, 
Florian et al, 2011, Alexandrou et al, 2006). Based on moxifloxacin effect on QT interval 
duration, it has been used standardly as a positive control in most thorough-QT (TQT) 
studies to determine study sensitivity. 
Following administration of the usual therapeutic dose (400 mg) under fasting conditions, 
Cmax occurs at approximately 1.5 hours and the t½ of moxifloxacin is approximately 
13 hours. Moxifloxacin can be given concurrently with food, but not with antacids containing 
magnesium or aluminum or preparations containing sucralfate or metal cations, such as iron 
or zinc. Coadministration with a high fat meal (i.e., 500 calories from fat) does not affect the 
overall absorption and systemic exposure to moxifloxacin, but increases the time to 
maximum blood concentration (to approximately 2.5 hours) and decreases the maximum 
blood concentration (Avelox 2019). 
Moxifloxacin prolongs QT interval duration and is used as a positive control in most TQT 
studies to determine study sensitivity. 
The most common AEs seen with moxifloxacin are nausea, diarrhea, headache, and 
dizziness. Moxifloxacin is in the FDA pregnancy category C. 


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8.3 
Rationale 
8.3.1 Rationale for this Study and Study Design 
Regulatory guidance (ICH E14 2005) has emphasized the need to obtain clear robust data on 
the effect of new chemical entities on ECG parameters with focus on cardiac repolarization 
as measured by the QTc duration. Though many Phase I, II, and III trials may be conducted, 
they usually have insufficient sample size, infrequent sampling of ECG data, or the use of 
inadequate controls to overcome the high rate of spontaneous change in QTc duration. This 
has resulted in regulatory guidance recommending a dedicated or thorough trial to define the 
ECG effects of new drugs. 
This study will be performed in healthy subjects to eliminate variables known to have an 
effect on ECG parameters (e.g., concomitant drugs, diseases). A supratherapeutic dose of 
BL-8040 is required to mimic the exposure in healthy subjects that may occur in the target 
patient population under the worst of circumstances (e.g., intrinsic or extrinsic factors such as 
DDIs, impaired hepatic or renal function, presence of heart disease, taking more than the 
clinical dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
The random order design of treatment sequence used the following 12-sequence scheme, 
with subjects randomly assigned to a sequence, as shown in Table 4. This schedule allows for 
blinding of all but the moxifloxacin treatment sequence, and does not require equal numbers 
of subjects in each sequence. 
The washout period between dosing in each period is considered sufficient to prevent 
carryover effects of the preceding treatment. 
8.3.2 Rationale for the Dose Selection 
As a peptide, and based on nonclinical and clinical data, BL-8040 exposure is not expected to 
be significantly increased by the intrinsic or extrinsic factors which may alter the exposure of 
small molecules (meal status, DDIs, hepatic insufficiency, or renal insufficiency). BL-8040 
and metabolic breakdown products are also not expected to accumulate with repeated dosing. 
In the absence of significant accumulation with repeated dosing or the need to slowly 
up-titrate the dose of a new drug, a crossover study design is preferred for a dedicated QT 
trial, as subjects act as their own controls. The dosage of BL-8040 used clinically is expected 
to be 1.25 mg/kg administered SC once daily, as a single dose or repeated dosing depending 
on the indication. There does not appear to be significant accumulation of BL-8040 following 
repeated administration for up to 7 days (Section 8.1.5). Therefore, a single-dose, crossover 
design is appropriate. The clinical/therapeutic dose of BL-8040 to be administered in this 
trial will therefore be 1.25 mg/kg as a single SC dose. 
The maximum tolerated dose of BL-8040 has not been established. Based on the results of 
healthy subject and patient studies, a 1.25 mg/kg SC dose has been well tolerated and results 
in a median Cmax of approximately 1600 ng/mL. BL-8040 is rapidly metabolized, and DDIs 
are not anticipated to result in elevated BL-8040 exposures. The highest clinically relevant 


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exposure is anticipated to be approximately a 1.5 fold multiple of the exposure following 
administration of the therapeutic dose. Doses of up to 2 mg/kg for 7 consecutive days have 
been administered to patients with good tolerability (Study BL-8040.01). A single 2 mg/kg 
SC dose, 1.6 times the anticipated clinical dose of 1.25 mg/kg, will therefore be utilized as 
the supratherapeutic dose. The supratherapeutic dose is anticipated to yield a Cmax of 
2600-5600 ng/mL, which is anticipated to be 1.6 to 3.5-fold higher than the Cmax which will 
be achieved with the clinical dose. It is anticipated that this supratherapeutic exposure will 
adequately cover the highest clinically relevant exposure for BL-8040. Based on the data 
from the single ascending dose study, there is not expected to be significant accumulation of 
BL-8040, nevertheless, a washout will be included between treatment periods. 
An oral 400 mg moxifloxacin will be used as a positive control (Florian et al, 2011) to 
determine the “assay sensitivity” of this study with an expected magnitude change from 
baseline placebo-corrected of 5-10 msec using a time-averaged analysis or 10-15 msec using 
a time-matched analysis. Moxifloxacin has been shown, in crossover design studies, to 
produce peak prolongation for ΔΔQTc ranging from 10 to 15 msec. The current study was 
designed to detect an increase of 5 msec in the QTc threshold of regulatory concern, 
i.e., lower bound of a one-sided 95% CI > 5 msec (Avelox 2019, Stass et al, 1998; 
Taubel et al, 2014). 
8.3.3 Rationale for Premedication Selection 
Based on experience in clinical studies to date, the most common adverse reactions observed 
following BL-8040 treatment include local injection site reactions including pain, erythema, 
oedema, pruritus and systemic reactions flushing, generalized pruritus, hot flushes, and 
urticaria. Two serious adverse reactions of anaphylaxis have occurred following BL-8040 
treatment. Premedication with antihistamines including cetirizine (H1 blocker) and nizatidine 
(H2 blocker), as well as and montelukast (leukotriene antagonist) is recommended in order to 
prevent or minimize these reactions. Furthermore, an analgesic (acetaminophen) is 
recommended to reduce the injection site pain. 
The timing of premedication administration in all BL-8040 clinical studies is 1 hour prior to 
study drug administration to allow for onset of pharmacological activity of premedication. 
Based on this, premedication will be administered 1 hour (± 15 minutes) prior to study drug 
administration and prior to the first cardiodynamic ECG baseline measurement scheduled 
at -0.75 hours predose. 
8.4 
Risks and/or Benefits to Subjects 
The therapeutic (1.25 mg/kg) and supratherapeutic (2 mg/kg) doses of BL-8040 administered 
in this study are not anticipated to induce any potential risk or benefit to subjects 
participating in this study. The exposure levels are expected to be tolerable for the subjects 
and without any major safety concern. Expected AEs are reported in the IB (IB v8.0, 2020). 
The moxifloxacin dosing regimen for this study is within the FDA-approved dosing regimen. 
It has been marketed in the US since 1999 as Avelox® and continues to be marketed in the 


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generic form. The risk of moxifloxacin-induced Torsade de Pointes is expected to be minimal 
when a single dose of the drug is administered at the recommended dose (Avelox 2019). 
The safety monitoring practices employed by this protocol (i.e., AEs, 12-lead safety ECG, 
vital sign measurements, clinical laboratory tests, and physical examination) are adequate to 
protect the subjects’ safety and should detect all expected treatment-emergent AEs (TEAEs). 
Premedication (as detailed in Section 12.1) will be administered to all subjects prior to 
dosing in each period as to minimize the risk of injection-related reactions. 
There will be no direct health benefit for study participants from receipt of study drug. An 
indirect health benefit to the healthy subjects enrolled in this study is the free medical tests 
received at Screening and during the study. 
 
 




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10 STUDY DESIGN 
10.1 Overall Study Design and Plan 
This is a randomized, double-blind (in respect to BL-8040 and BL-8040-matching placebo 
dosing), placebo- and positive-controlled, 4-period, 4-way crossover study. 
Approximately 40 healthy, adult male and female subjects will be enrolled to ensure at least 
26 subjects complete the study. Every attempt will be made to enroll no less than 30% of 
either gender. 
Screening activities will occur within 28 days prior to check-in (Day -2 in Period 1). 
Subjects who are found to be eligible following screening procedures will be invited and 
admitted to the CRU on Day -2 of Period 1 and will remain at the CRU until the end of 
Period 4 (Section 10.1.1). 
A continuous 12-lead cardiodynamic ECG recording will be collected for approximately 
24 hours on Day -1 of Period 1 for use in the optimized QTcI baseline calculations. 
On Day 1 of Period 1, subjects will be randomized to 1 of 12 treatment sequences (Table 4). 
Each treatment sequence comprises 4 treatment periods. 
On Day 1 of each period, subjects will receive single-dose SC injection of BL-8040 
(therapeutic or supratherapeutic dose), single-dose SC injection of BL-8040-matching 
placebo, or a single oral dose of moxifloxacin. Cardiodynamic readings, plasma PK samples, 
and blood PD samples will be collected at different time points prior to dosing and up to 
24 hours postdose in each period, as appropriate. 
There will be a washout period of 5-7 days between dosing in each period. 
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations 
(e.g., AEs, 12-lead safety ECG, vital sign measurements, clinical laboratory tests, and 
physical examination). 
Early discontinued subjects will not be replaced. 
10.1.1 Confinement and Follow-Up 
Subjects will be housed in the CRU on Day -2 of Period 1, at the time indicated by the CRU, 
until after completion of study procedures on Day 2 of Period 4. 
At all times, a subject may be required to remain at the CRU for longer at the discretion of 
the Principal Investigator (PI) or designee. 
All subjects who received at least one dose of any study drug (including subjects who 
terminate the study early) will return to the CRU 7 ± 2 days after the last dose for follow-up 


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procedures, and to determine if any AE has occurred since the last study visit. A review of 
AEs and concomitant medication will also be performed at this follow-up visit. 
10.1.2 End of Study Definition 
The end of study is defined as the date of the last scheduled study procedure (i.e., 7 ± 2 days 
after the last dose of study drug) as outlined in the Study Events Flow Chart (Section 6). 


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11 STUDY POPULATION 
11.1 Inclusion Criteria 
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in 
the study: 
1. Healthy, adult, males and females between the ages of 18 and 55 years, inclusive, at 
Screening. 
2. Body weight between 50-109 kg (inclusive) and body mass index (BMI) within 
18.0-29.99 kg/m2 (inclusive) at Screening. 
3. Medically healthy with no clinically significant medical history, physical examination, 
laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. 
4. Current non-smokers who have not used any nicotine-containing products (chewed or 
smoked) or replacement products including electronic cigarettes for at least 3 months 
prior to first dosing. 
5. Women must meet one of the following criteria: a) postmenopausal; b) surgically sterile; 
c) of childbearing potential and practicing contraception, as described below: 
• Postmenopausal (postmenopausal women must have no menstrual bleeding for at 
least 1 year prior to first dosing and menopause is confirmed by FSH levels consistent 
with postmenopausal status), or 
• Surgically sterile (e.g., hysterectomy, bilateral oophorectomy, hysteroscopic 
sterilization) for at least 6 months prior to first dosing, or 
• Women of childbearing potential must be non-lactating and agree to either using a 
highly effective acceptable form of birth control (e.g., non-hormonal intrauterine 
device plus condom and spermicide). 
6. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain 
from sexual intercourse during the study until 90 days after the last dosing. (No 
restrictions are required for a vasectomized male provided his vasectomy has been 
performed 4 months or more prior to the first dosing. A male who has been vasectomized 
less than 4 months prior to study first dosing must follow the same restrictions as a 
non-vasectomized male.) 
7. If male, must agree not to donate sperm from the first dosing until 90 days after the last 
dosing. 
8. Understands the study procedures in the informed consent form (ICF), and is willing and 
able to comply with the protocol. 


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11.2 Exclusion Criteria 
Subjects must not be enrolled in the study if they meet any of the following criteria: 
1. Past or present diseases, which, as judged by the PI or designee, may affect the outcome 
of this study or pose an additional risk to the subject by their participation in the study, 
including, but not limited to, significant medical abnormality including: psychiatric, 
neurologic, pulmonary, cardiac, gastrointestinal, genitourinary, renal, metabolic, 
endocrinologic, or autoimmune disorder. 
2. Is mentally or legally incapacitated or has significant emotional problems at the time of 
the Screening visit or expected during the conduct of the study. 
3. Positive result for human immunodeficiency virus (HIV), hepatitis B surface antigen 
(HBsAg), or hepatitis C virus (HCV) antibody at Screening. 
4. Family history of QTc prolongation or of unexplainable sudden death at <50 years of age. 
5. History or presence of any of the following: 
• sick sinus syndrome, second or third degree atrioventricular block, myocardial 
infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, 
prolonged QTcF interval, or conduction abnormalities; 
• ischemic heart disease, symptomatic arrhythmias, or poorly controlled hypertension. 
6. Knowledge of any kind of cardiovascular disorder/condition known to increase the 
possibility of QT prolongation or history of additional risk factors for torsade de pointes 
(e.g., heart failure, clinically significant hypokalemia, family history of Long QT 
Syndrome or Brugada Syndrome) or cardiac conduction disorders. 
7. Any condition that may interfere with the absorption, metabolism, or elimination of the 
study drug. 
8. History of, or active, alcohol or illicit drug abuse as defined by the Diagnostic and 
Statistical Manual of Mental Disorders, fourth edition, manual, within 2 years prior to the 
first dosing. Alcohol abuse is defined as an average intake of two or more drinks (12 oz 
beer, 1.5 oz of hard liquor, or equivalent) per day. 
9. Laboratory safety test results that are outside of the normal reference ranges (unless 
clinically acceptable to the PI or designee) at Screening. 
10. Resting supine HR <50 bpm or >100 bpm at Screening or check-in (Day -2). Minor 
deviations will be acceptable if considered to be of no clinical significance by the PI or 
designee. 
11. Resting supine systolic blood pressure <90 mmHg or >140 mmHg; resting supine 
diastolic blood pressure <50 mmHg or >90 mmHg at Screening or check-in.  


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12. Significant history or presence of ECG findings at Screening or check-in (Day -2), 
including: 
• QTcF >450 msec 
• QRS >110 msec, if >110 msec, result will be confirmed by a manual over read 
• PR >200 msec 
• Second or third-degree atrioventricular (AV) block. 
13. Significant history or presence of ECG findings as judged by the PI or designee at 
Screening or check-in (Day -2), including: 
• ECG abnormalities which interfere with accurate QT measurement 
• T wave flattening or other abnormalities which in the opinion of the PI (or designee) 
may interfere with the analysis of QT intervals 
• Any rhythm other than sinus rhythm, which is interpreted by the PI (or designee) to be 
clinically significant. 
14. Significant safety laboratory abnormalities that would place the subject at undue risk in 
the PI or designee’s opinion, including but not limited to serum alanine aminotransferase 
(ALT) or serum aspartate aminotransferase (AST) >1.2 x upper limit of normal at 
Screening or check-in. 
15. Positive urine cotinine at Screening. 
16. Unable to refrain from or anticipates the use of: 
• Any drug, including prescription and non-prescription medications, herbal remedies, 
or vitamin supplements beginning 14 days or 5 half-lives (whichever is longer) prior 
to the first dosing or likelihood that such treatment will be needed at any time during 
the study (unless approved in advance by the Sponsor). Medications listed in 
Section 11.4.2 will be allowed. 
17. Participation in another clinical study within 30 days prior to the first dosing. The 30-day 
window will be derived from the date of the last blood collection or dosing, whichever is 
later, in the previous study to Day 1 of Period 1 of the current study. 
18. Donation of blood or blood loss >500 mL within the 56 days prior to the first dosing. 
19. Plasma donation within 7 days prior to the first dosing. 
20. Any condition or situation that, in the opinion of the PI or designee, would prevent proper 
evaluation of the safety, PK, and/or PD of the study drug according to the study protocol 
(e.g., poorly compliant subject, poor venous access, allergies to medical 
plastics/latex/adhesive dressing/medical tape). 
21. History of hypersensitivity or allergy to moxifloxacin or any study medication. 


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22. History of tendonitis or tendon rupture with moxifloxacin or any other quinolone type 
drug. 
23. History of unexplained loss of consciousness, unexplained syncope, near drowning with 
hospital admission. 
24. Use of any marijuana product within 6 months prior to the first dosing. 
25. Use of illicit drugs or tetrahydrocannabinol-containing medicines within 6 months prior 
to the first dosing. 
26. Female subjects with a positive pregnancy test at Screening or check-in or lactating. 
27. Positive urine drug or alcohol results at Screening or check-in. 
28. Has tattoo(s) or scarring at or near the site of injection or any other condition which may 
interfere with injection site examination, in the opinion of the PI or designee. 
29. Subjects intending to lose weight during the study. 
11.3 Early Termination of Subjects from the Study 
Subjects are free to withdraw from the study at any time for any reason. 
Subjects’ participation in the study maybe discontinued due to the following reasons: 
• Subjects withdrew consent. 
• Request of the Sponsor. 
• Request of the PI or primary care physician. 
• Non-adherence to study requirements, e.g., difficulties on blood collection. 
• Protocol violation. 
• AEs. 
• Death. 
• Pregnancy. 
• QTcF interval > 500 msec, confirmed on recheck within 5 minutes, on any scheduled 
safety ECG or at any time an unscheduled ECG for safety was deemed necessary by 
the PI, or an increase > 60 msec from baseline. 
• Lost to follow-up. 
If a subject is withdrawn from the study due to any of the reasons above, every effort should 
be made to determine the reason and all procedures for early termination should be 
performed. 


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11.4 Study Restrictions 
11.4.1 Prohibitions 
Consumption of foods and beverages containing the following substances will be prohibited 
as indicated: 
• Xanthines/caffeine: 24 hours prior to the first dose and until collection of the last PK 
sample; 
• Alcohol: 72 hours prior to the first dose and until collection of the last PK sample; 
• Grapefruit/Seville orange: 7 days prior to the first dose and until collection of the last 
PK sample. 
11.4.2 Concomitant Medication 
Concomitant medications will be prohibited as listed in the exclusion criteria in Section 11.2.  
Premedication as described in Section 12.1 will be allowed. 
Treatment of AEs may include the following medication:  hydrocortisone (100 mg IV), other 
steroids (oral, topical, or IV), anti-histamines, and/or analgesics (e.g., acetaminophen up to 
2 g per 24 hours, ibuprofen up to 1.2 g per 24 hours) may be administered at the discretion of 
the PI or designee to treat systemic reactions and injection site reactions (Section 12.7). 
Negative chronotropic drugs, such as beta blockers, should be avoided as rescue medication. 
If deviations occur, the PI or designee in consultation with the Sponsor if needed will decide 
on a case-by-case basis whether the subject may continue participation in the study. 
All medications taken by subjects during the course of the study will be recorded. 
11.4.3 Meals 
Water (except water provided with each dosing) will be restricted 1 hour prior to and 1 hour 
after each oral dosing, but will be allowed ad libitum at all other times. Other fluids may be 
given as part of meals and snacks but will be restricted at all other times throughout the 
confinement period. 
In each period, subjects will fast overnight for at least 10 hours prior to each dosing and will 
continue the fast for at least 4 hours postdose. 
On Day -1 of Period 1, subjects will follow a similar time matched (± 5 minutes) fasting and 
meal schedule as planned for Day 1 of Period 1 according to the anticipated time of dosing 
on Day 1 of Period 1. 
When scheduled at the same time, meals and snacks will be provided following completion 
of the cardiodynamic reading and must be scheduled to be completed at least 60 minutes 


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before any scheduled ECG time point (i.e., standard 12-lead safety ECG or cardiodynamic 
ECG). Subjects are not required to consume meals or snacks in their entirety. 
When confined, standard meals and snacks will be provided at appropriate times, except 
when they are required to fast. When confined in the CRU, subjects will be required to fast 
from all food and drink except water between meals and snacks. 
Each meal and/or snacks served at the CRU will be standardized and will be similar in 
caloric content and composition and will be taken at approximately the same time in each 
period. 
11.4.4 Activity 
Subjects must be awakened at least 1 hour prior to the start of the cardiodynamic ECG 
recording on Day -1 of Period 1 and Day 1 of each period. On Day 1 of each period, subjects 
will remain awake until after data collection at the 16-hour time point, as the QT-RR 
relationship is different during sleep. Subjects must also be awakened at least 1 hour prior to 
the cardiodynamic ECG recording at the 24-hour time point in each period. 
Subjects will remain ambulatory or seated upright for the first 4 hours postdose, except when 
they are supine or semi-reclined for study procedures. After the first 4 hours postdose, 
subjects will remain ambulatory, seated upright, or semi-reclined and awake, except when a 
supine position is dictated by study procedures, until the 16-hour postdose cardiodynamic 
ECG recording. Subjects must rest in the supine position for at least 10 minutes prior to each 
ECG extraction window and throughout the duration of the ECG extraction window with 
minimal movement and minimal exposure to noise and other environmental stimuli. 
However, should AEs occur at any time, subjects may be placed in an appropriate position or 
will be permitted to lie down on their right side. 
Subjects will be instructed to refrain from strenuous physical activity which could cause 
muscle aches or injury, including contact sports at any time from screening until completion 
of the study. 
 


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12 TREATMENTS 
12.1 Premedication Administered 
Nizatidine 15 mg/mL oral solution, cetirizine hydrochloride 10 mg tablets, acetaminophen 
500 mg tablets, and montelukast sodium 10 mg tablets will be provided. 
In each period, the following medications will be administered 1 hour (± 15 minutes) prior to 
study drug administration and prior to the first baseline cardiodynamic ECG measurement 
scheduled at the -0.75 hour time point: 
• 300 mg nizatidine (H2 blocker), single oral dose 
• 10 mg cetirizine (H1 blocker), single oral dose 
• 1 g acetaminophen (analgesic), single oral dose 
• 10 mg montelukast (mast cell stabilizer), single oral dose 
The time of premedication administration is to be recorded on site documentation and in the 
case report form (CRF). 
12.2 Treatments Administered 
Both BL-8040 and BL-8040-matching placebo will be provided as lyophilized powder for 
reconstitution with 2 mL sterile 0.45% sodium chloride (half saline) prior to SC injection. 
BL-8040 drug product is formulated as a sterile and non-pyrogenic lyophilized powder in a 
vial containing 73 mg BL-8040 free base peptide (on dry basis) and 26 mg of mannitol. 
BL-8040-matching placebo is formulated as a sterile and non-pyrogenic lyophilized powder 
in a vial containing 50 mg of mannitol. 
BL-8040 and BL-8040-matching placebo is to be administered by slow SC injection of at 
least 2 minutes per syringe. If the total volume to be administered exceeds ~2 mL then 
dosing should be divided into two or more syringes to be administered. Each syringe, for the 
same treatment, should be administered to a different location within the same body area. At 
the PI’s discretion, a different body area may be used for the same treatment, as needed. All 
subjects are to remain under surveillance for at least 2 hours after SC dosing. 
To ensure blinding for the SC dosing, each subject will receive the same total injection 
volume in each SC dosing period. Subject’ weight at check-in (Day -2 of Period 1) will be 
used to calculate the BL-8040 (and BL-8040-matching placebo) doses. 
Prior to each SC injection, the site of injection will be examined. 
Consistent use of the same body area of injection in all subjects for all SC dosing periods is 
preferred. 
Moxifloxacin will be supplied as 400 mg moxifloxacin hydrochloride tablets. Moxifloxacin 
will be administered orally with approximately 240 mL of water. Subjects will be instructed 
not to crush, split, or chew the tablet. 


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An unblinded pharmacist will be responsible for preparing BL-8040 or BL-8040-matching 
placebo and moxifloxacin tablets in individual unit dose containers for each subject and for 
each treatment to the blinded study personnel for administration as per the randomization 
scheme. Moxifloxacin dosing will be open-label. 
Additional instructions for study drug preparation and administration will be provided in a 
separate pharmacy document. 
Treatments are described as follows: 
Treatment A: 
(Therapeutic) 
1.25 mg/kg BL-8040 + BL-8040-matching placebo administered 
via SC injection 
Treatment B: 
(Supratherapeutic) 
2 mg/kg BL-8040 administered via SC injection 
Treatment C: 
(Placebo Control) 
BL-8040-matching placebo administered via SC injection 
Treatment D: 
(Positive Control) 
400 mg moxifloxacin (1 x 400 mg tablet) administered orally 
For each subject, an appropriate volume of BL-8040-matching placebo will be used in 
Treatments A and C such that the total volume administered for each of Treatments A and C 
will be the same as the total volume injected in Treatment B. 
All study drugs will be administered on Day 1 following an overnight fast. Hour 0 on Day 1 
will be set as the start of dosing. 
12.3 Dose Modification 
The dose and administration of the study drug to any subject may not be modified. If 
necessary a subject must be discontinued for the reasons described in Section 11.3. 
12.4 Treatment Compliance 
Before and after the SC injection, the qualified designee will visually inspect the syringe to 
ensure that the subject has received the entire dose. In the case of an incomplete dosing in the 
opinion of the PI (or designee) and/or Sponsor, the subject may be withdrawn. 
A qualified designee will be responsible for monitoring the administration of the timed oral 
(moxifloxacin) doses. A mouth check will be performed by the qualified designee to ensure 
that the subjects have swallowed the study drug. Once a subject has finished the dosing 
water, the qualified designee will use a flashlight and a tongue depressor to check the 
subject’s mouth. Subjects’ hands will also be verified to ensure that the study drug was 
ingested. 


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12.5 Method of Treatment Assignment and Treatment Sequence 
Each subject will be assigned a unique identification number upon screening. Subjects who 
complete the study screening assessments and meet all the eligibility criteria will be assigned 
a unique randomization identification number at the time of the first dosing, different from 
the screening number, and will receive the corresponding study drug, according to a 
randomization scheme.  
Subjects will receive each of Treatments A, B, C, and D, in a pre-defined order according to 
the sequence scheme determined at randomization. The sequences to be used in the 
randomization are detailed in Table 4. 
Early discontinued subjects will not be replaced. 
Table 4: Design of Treatment Sequences 
Sequence 
Period 1 
Period 2 
Period 3 
Period 4 
1 
A 
B 
C 
D 
2 
B 
D 
A 
C 
3 
C 
A 
D 
B 
4 
D 
C 
B 
A 
5 
B 
C 
A 
D 
6 
C 
D 
B 
A 
7 
A 
B 
D 
C 
8 
D 
A 
C 
B 
9 
C 
A 
B 
D 
10 
A 
D 
C 
B 
11 
B 
C 
D 
A 
12 
D 
B 
A 
C 
Treatments A, B, C, and D are described in Section 12.2. 
12.6 Blinding 
This is a double-blind study in respect to BL-8040 and BL-8040-matching placebo dosing. 
Moxifloxacin, the positive control, will be administered as open-label. 
12.6.1 Maintenance of Randomization 
A computerized randomization scheme will be created by a 
 statistician and it shall 
be considered blinded for BL-8040 dosing (as per the following). 
The randomization is available only to the CRU pharmacy staff that is preparing the drug 
who will not be involved in any other aspect of the study including administration of the drug 
and to the Sponsor pharmacovigilance representative and other personnel that will be defined 
by the Sponsor. It will not be made available to other members of the Sponsor, 
subjects, or members of the staff responsible for the 
monitoring and evaluation of safety assessments. 


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12.6.2 Procedures for Breaking the Blind Prior to Study Completion 
One set of sealed envelopes containing the randomization code will be supplied to the PI or 
designee at the start of the study. 
Breaking of the blind is expressly forbidden except in the event of a medical emergency 
where the identity of the drug must be known in order to properly treat the subject or in the 
event of an interim analysis.  
In the event of a medical emergency, it is requested that the PI or designee make every effort 
to contact the Study Monitor or designee prior to breaking the blind. If breaking the blind is 
required because of a medical emergency, the treatment identity would be revealed by the PI 
or designee, for that subject only. In the event that the emergency is one, in which it appears 
that the other subjects may be at imminent risk, the blind may be broken for all subjects 
dosed at that dose level. The unblinding will be properly documented in the study file. 
In all cases where the code is broken, the PI or designee should record the date and reason for 
code breaking. 
At the end of the study, envelopes will be retained according to site procedures unless 
specified otherwise by the Sponsor. 
12.6.3 Revealing of Randomization 
In the absence of a medical emergency, the blinded randomization for this study will not be 
revealed until all data are entered in the database, edits checks are performed, queries closed, 
and the database is officially locked. 
12.7 Rescue Medication 
In the event of an injection reaction, subjects may be treated with IV 100 mg hydrocortisone 
at the discretion of the PI. 
Other steroids (oral, topical, and/or IV), anti-histamines, analgesics, or other medication 
(e.g., montelukast) according to the PI or designee judgment may also be administered to 
treat systemic reactions and injection site reactions. Negative chronotropic drugs, such as 
beta blockers, should be avoided as rescue medication. 
A saline lock will be placed for at least approximately the first 2 hours following dosing to 
ensure rapid administration of rescue medication, if necessary. 


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13 STUDY ASSESSMENTS AND PROCEDURES 
The Study Events Flow Chart (Section 6) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. 
Additional evaluations/testing may be deemed necessary by the PI or designee and/or the 
Sponsor for reasons related to subject safety. 
For this study, the cardiodynamic recording via ECG extractions from the Holter monitor and 
the PK blood samples are the critical parameters. Cardiodynamic recording via ECG 
extractions will be completed prior to the PK blood samples collected as close to the exact 
time point as possible. All other procedures should be completed as close to the 
prescribed/scheduled time as possible, but can be performed prior or after the 
prescribed/scheduled time. 
When scheduled at the same time point, study procedures (excluding those at screening and 
check-in) will be performed in the following order (below) with regard to the prescribed 
time: 
a. 12-lead safety ECGs 
b. Cardiodynamic ECG recording extraction 
c. Blood sample(s) collection (to be collected as close to the exact time point as 
possible) 
d. Standardized meal or snack (meals and/or snacks must be completed at least 1 hour 
before any Holter recording extractions and/or safety ECG tracings) 
Vital signs may be performed either before or after blood sample collection(s). 
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 
13.1 Screening 
Within 28 days prior to check-in, medical history and demographic data, including name, 
sex, age, race, ethnicity, body weight (kg), height (cm), BMI (kg/m2) and history of tobacco 
use will be recorded. Each subject will have a 12-lead safety ECG, vital sign measurements 
(HR, blood pressure, temperature, and respiratory rate), clinical laboratory tests and 
additional tests as noted in Section 13.2.5, and physical examination. 
13.2 Safety Assessments 
13.2.1 Physical Examination 
A full physical examination will be performed as outlined in the Study Events Flow Chart 
(Section 6). Symptom-driven physical examinations may be performed at other times, if 
deemed necessary by the PI or designee. 


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13.2.2 Vital Signs 
Single measurements of body temperature, respiratory rate, blood pressure, and HR, will be 
measured as outlined in the Study Events Flow Chart (Section 6). Unscheduled vital signs 
may be taken at any other times, if deemed necessary. 
Blood pressure and HR measurements will be performed with subjects in a supine position, 
except when they are seated or semi-reclined because of study procedures and/or AEs 
(e.g., nausea, dizziness) or if deemed necessary by the PI or designee. 
When scheduled postdose, vital signs will be performed within approximately 30 minutes of 
the scheduled time point. 
13.2.3 ECG Monitoring 
For study conduct, 12-lead ECGs will be classified as 12-lead safety ECGs or cardiodynamic 
ECGs and will be performed as outlined in the Study Events Flow Chart (Section 6). 
ECG data will be will be obtained digitally using a Global Instrumentation (Manlius, New 
York, USA) M12R continuous 12-lead ECG digital recorder. The ECGs will either be 
collected via Bluetooth and available for real time safety review or will be stored as a 
continuous 12-lead ECG recording on a flash card (Holter recording for cardiodynamic ECG 
extraction) and are not available for review until the data is downloaded after the 24-hour 
recording has ended. 
A subject will be withdrawn from the study by the PI or designee if, in their medical 
judgment, ECG findings are present which make continued study participation not in the 
subject’s best interest. In this case, if deemed clinically significant per PI, this should be 
reported within the CRF as an AE and the reason for discontinuation should be due to AE. 
13.2.3.1 
12-Lead Safety ECGs 
Single 12-lead safety ECGs will be performed as outlined in the Study Events Flow Chart 
(Section 6). Additional ECGs may be taken at any other times, if deemed necessary by the PI 
or designee.  
12-lead safety ECGs will be collected with subjects in a supine position in a quiet 
environment. All ECG tracings will be reviewed by the PI or designee. Intervals for 12-lead 
safety ECGs will be classified as normal, not clinically significant, or clinically significant. 
The 12-lead safety ECG data, including all time points, will be recorded in the CRF and be 
used to determine subject eligibility, evaluate general cardiac safety parameters for subjects 
during the study and to evaluate cardiac related AEs. 
When scheduled postdose, ECGs will be performed within approximately 30 minutes of the 
scheduled time point. 


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13.2.3.2 
Cardiodynamic ECGs 
Holter monitors will be used to collect continuous 12-lead ECG data for the purpose of 
collecting cardiodynamic ECGs. Recording will be started and stopped at logistically optimal 
times to ensure that all scheduled time points are collected.  
ECGs will be obtained as replicate (up to 10) 12-lead ECGs within each extraction window 
at each time point and will be downloaded from the M12R flash card on Day 1 of each 
treatment period. Replicate 12-lead ECGs will be extracted within a 5-minute time window 
around the scheduled time points as outlined in the Study Events Flow Chart (Section 6) but 
prior to the PK blood sample collection. 
Timing and recording technique for ECGs will be standardized for all subjects. Subjects will 
be required to lie quietly in a supine position with minimal movement and minimal exposure 
to noise and other environmental stimuli (e.g., TV, loud radio, interactions with other 
participants, etc.) for at least 10 minutes prior to each ECG extraction and throughout the 
duration of the extraction to allow for quality ECG extraction. All ECG extractions should 
occur in a 5-minute time window prior to the PK blood samples which should be collected as 
close to the exact scheduled/nominal time point as possible. If extracted ECGs from targeted 
time points are artefactual or of poor quality, analyzable 14-second ECGs will be extracted as 
close as possible to the targeted time points. 
Nominal time of the ECG recording will be used for the cardiodynamic analysis. 
The 12-lead Holter and ECG equipment will be supplied and supported by 
 
 The continuous 12-lead digital ECG data will 
be stored onto Secure Digital™ memory cards. ECGs to be used in the analyses will be 
selected by pre-determined time points as outlined in the Study Events Flow Chart 
(Section 6), and will be read centrally by the Core ECG Laboratory.  
The principles to be followed at the Core ECG Laboratory and a brief description of ECG 
analysis methods utilized by 
 core laboratory are described as follows: 
• ECG analysts are blinded to the subject, visit, and treatment randomization. 
• Baseline and on-treatment ECGs for individual subjects will be analyzed for the same 
lead and will be analyzed by the same reader. 
• The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead 
for analysis will be changed to another lead for the entire subject data set. 
The following is a brief description of ECG analysis methods utilized by the 
 core 
laboratory. 
13.2.3.2.1 TQT Plus ECG Extraction Technique 
The core laboratory will use TQT Plus, an advanced computer-assisted and statistical process 
utilized to extract ECGs from continuous 24-hour recordings collected in TQT studies. 
During protocol-specified ECG extraction windows, 10-second digital 12-lead ECG tracings 
will be extracted from continuous recordings. The TQT Plus method enables the extraction of 


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a high-quality data set by identifying periods of recordings with the lowest available HR 
variability and noise. 
The ECGs will be extracted according to the following principles: 
• The actual times of dosing, extraction windows, and PK sampling will be 
communicated to the central ECG laboratory by the CRU personnel. 
• The TQT Plus process will identify periods of stable HR on the continuous 12-lead 
ECG tracing within the 5-minute extraction window. Stability will be defined as 
variation in the HR and other ECG parameters from beat-to-beat lower than a 
predefined threshold. If the TQT Plus method results in a low number of consecutive, 
readable cardiac cycles in the 5-minute time point, the time point will be fully 
reviewed manually. 
• Replicate, non-overlapping 10-second ECGs will be extracted in close succession 
within each extraction window. 
13.2.3.2.2 Expert-Precision QT Analysis 
At each nominal time point specified in the protocol, up to 10 ECG replicates will be 
extracted with TQT Plus methods. All readable cardiac cycles from these ECG replicates will 
be assessed for multiple quality metrics, including beat stability, HR changes, noise, and 
other parameters, and will be categorized into high and low confidence rank. All low 
confidence beats will be fully reviewed and adjudicated manually by ECG technicians using 
pass-fail criteria. The beats found acceptable by manual review will be included in the 
analysis. 
The primary analysis lead will be Lead II. If Lead II is not analyzable, then the primary lead 
of analysis will be changed to Lead V2 for the subject’s entire data set. If Lead V2 is not 
analyzable, then Lead V5 will be used for the subject’s entire data set. If both alternate leads 
cannot be used, the data may be deemed non-analyzable or the 
 cardiologist may decide 
the most appropriate lead to use for the subject’s entire data set. The lead used for analysis 
will be listed in the data listings transferred from 
 
ECG morphology analysis and measurement of PR and QRS intervals will be fully 
performed manually in 3 of the 10 ECG replicates at each time point. Final quality control 
and diagnostic interpretations will be performed by the cardiologist. When the results for 
each time point are compiled in the final data set, the comparison will be made between ECG 
parameters from the 3 manually reviewed ECGs versus the 10 ECG replicates for quality 
control purposes. If significant differences are found, the entire time point will be reviewed 
manually. 
13.2.3.2.3 Cardiodynamic ECG Assessment 
A continuous 12-lead ECG and Holter data acquisition will be in place as outlined in the 
Study Events Flow Chart (Section 6). The continuous recording from Day -1 of Period 1 will 
be used for the Optimized QTcI Calculation, but not for standard ECG extractions. 


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The following ECG parameters will be measured and calculated: HR, RR, PR, QT, QTcF, 
QTcI, and QRS. Changes in ECG morphology will also be assessed. 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between BL-8040 and ∆QTcI with the intent to exclude an effect >10 msec at clinically 
relevant plasma concentrations of BL-8040. The relationship between BL-8040 plasma 
concentration and ΔQTcF will also be explored. 
In addition, the effect of BL-8040 on ∆∆QTcI, ΔΔQTcF, ΔΔHR, ΔΔPR, and ΔΔQRS will be 
evaluated at each postdose time point (‘by time point’ analysis). An analysis of categorical 
outliers will be performed for changes in HR, PR, QRS, QTc (QTcI and QTcF), as well as an 
analysis of new ECG morphology changes. 
Assay sensitivity will be evaluated by concentration-QTc analysis of the effect on ∆QTcI of 
moxifloxacin using a similar model as for the primary analysis, as will be detailed in the 
SAP. 
13.2.4 Height, Body Weight, and BMI 
Height and body weight (kg) will be reported as outlined in the Study Events Flow Chart 
(Section 6). 
The Screening height measurement will be used for BMI calculations throughout the study. 


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13.2.5 
Clinical Laboratory Tests 
All tests listed below will be performed as outlined in the Study Events Flow Chart 
(Section 6). In addition, laboratory safety tests may be performed at various unscheduled 
time points, if deemed necessary by the PI or designee. 
Hematology 
 
Serum Chemistry * 
• 
Hemoglobin 
• 
Hematocrit  
• 
Total and differential leukocyte 
count 
• 
Red blood cell count 
• 
Platelet count 
 
Coagulation 
• 
Prothrombin time/international 
normalized ratio and activated 
partial thromboplastin time 
 
 
• 
Blood Urea Nitrogen 
• 
Bilirubin (total and direct) 
• 
Alkaline phosphatase 
• 
Aspartate aminotransferase 
• 
Alanine aminotransferase 
• 
Albumin 
• 
Sodium 
• 
Potassium 
• 
Magnesium 
• 
Chloride 
• 
Glucose (fasting) 
• 
Creatinine ** 
 
Urinalysis 
 
Additional Tests 
• 
pH 
• 
Specific gravity 
• 
Protein *** 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Blood *** 
• 
Nitrite*** 
• 
Urobilinogen 
• 
Leukocyte esterase *** 
 
• 
HIV test 
• 
HBsAg 
• 
HCV 
• 
Urine drug screen 
 Opiates § 
 Opioids 
 Amphetamines 
 Barbiturates 
 Benzodiazepines 
 Cocaine 
 Cannabinoids 
• 
Urine alcohol screen 
• 
Serum pregnancy test (for females only) 
• 
FSH (for postmenopausal females only) 
 
* 
Serum chemistry tests will be performed after at least an 8-hour fast; however, in case of early 
discontinuation or rechecks, subjects may not have fasted for 8 hours prior to the serum chemistry sample 
is taken. 
** At screening, creatinine clearance will be calculated using the Cockcroft-Gault formula. 
*** If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination 
(for red blood cells, WBCs, bacteria, casts, and epithelial cells) will be performed. 


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13.2.6 Adverse Events 
13.2.6.1 
Adverse Event Definition 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. 
A suspected adverse reaction means any AE for which there is a reasonable possibility that 
the drug caused the AE. Reasonable possibility means there is evidence to suggest a causal 
relationship between the drug and the AE.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
13.2.6.2 
Monitoring 
Subjects will be monitored from the time of signing the ICF for adverse reactions to the study 
formulations and/or procedures. Prior to release, subjects will be asked how they are feeling. 
At each subsequent visit and at the beginning of subsequent periods, subjects will be queried 
with an open-ended question such as: ‘How have you been feeling since your last visit?’ 
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test 
value(s) will be evaluated by the PI or designee and treated and/or followed up until the 
symptoms or value(s) return to normal, or acceptable levels, as judged by the PI or designee.  
Treatment of serious adverse events (SAEs) will be performed by a licensed health care 
professional, either at 
 or at a nearby hospital emergency room where appropriate 
medical test(s) and/or examination(s) will be performed to document resolution of event(s). 
Outcome may be classified as recovered/resolved, recovered/resolved with sequelae, 
recovering/resolving, not recovered/not resolved, fatal, or unknown (lost to follow-up). 
13.2.6.3 
Reporting 
All AEs that occurred during this clinical study will be recorded. The PI or designee will 
review each event and assess its relationship to drug treatment (related or not related). Each 
sign or symptom reported will be graded on a 3-point severity scale (mild, moderate, or 
severe), and the date of onset, time of onset, and outcome of each event will be noted. 
The following definitions will be used for rating the severity of AEs: 
Mild 
The AE is easily tolerated and does not interfere with daily activity. 
Moderate 
The AE interferes with daily activity, but the subject is still able to function. 
Medical intervention may be considered. 
Severe 
The AE is incapacitating and requires medical intervention. 


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13.2.6.4 
Serious Adverse Event 
If any AEs are serious, as defined by the FDA Code of Federal Regulations (CFR), 
Chapter 21, special procedures will be followed. All SAEs will be reported to the Sponsor 
via fax or e-mail (
) within one working day of becoming aware of 
the event, whether or not the serious events are deemed drug-related. All serious event 
reporting will adhere to 21 CFR 312.32 for Investigational New Drugs (IND) and to the 
Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and 
BA/BE, dated December 2012. The institutional review board (IRB) will be notified of the 
Alert Reports as per FDA regulations. 
A SAE is any AE or suspected adverse reaction that in the view of either the PI (or designee) 
or Sponsor, results in any of the following outcomes: Death, a life-threatening AE, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in the above definition. 
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 inpatient hospitalization, or the development of drug dependency or drug abuse.  
Life-threatening is defined as an AE or suspected adverse reaction that in the view of the PI 
(or designee) or Sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an AE or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death. 
Unexpected is defined as an AE or suspected adverse reaction that is not listed in the IB or is 
not listed at the specificity or severity that has been observed; or is not consistent with the 
risk information described in the general investigational plan or elsewhere in the current 
application, as amended. 
If a SAE occurs to a subject on this study, contact the Sponsor personnel listed in Section 3. 
13.3 Pharmacokinetic Assessments 
13.3.1 Blood Sampling and Processing 
13.3.1.1 
BL-8040 (Motixafortide) 
For all subjects, blood samples for the determination of BL-8040 will be collected at 
scheduled time points as delineated in the Study Events Flow Chart (Section 6). 
Instructions for blood sampling, collection, processing, and sample shipment will be 
provided separately. 
The analytical laboratory measuring plasma concentrations of BL-8040 will be unblinded to 
the samples as their analyses will be related to treatments. 


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13.3.1.2 
Moxifloxacin 
For all subjects, blood samples for the determination of moxifloxacin will be collected at 
scheduled time points as delineated in the Study Events Flow Chart (Section 6). 
Instructions for blood sampling, collection, processing, and sample shipment will be 
provided separately. 
The analytical laboratory measuring plasma concentrations of moxifloxacin will be 
unblinded to the samples as their analyses will be related to treatments. Only samples from 
the period where subjects received moxifloxacin are planned to be analyzed. 
13.3.2 Pharmacokinetic Parameters 
The following PK parameters for plasma BL-8040 and moxifloxacin will be calculated, as 
appropriate: 
AUC0-t: 
 
The area under the concentration-time curve, from time 0 to the 
last observed non-zero concentration, as calculated by the linear 
trapezoidal method. 
AUC0-inf: 
The area under the concentration-time curve from time 0 
extrapolated to infinity. AUC0-inf is calculated as the sum of 
AUC0-t plus the ratio of the last measurable plasma concentration 
to the elimination rate constant. 
AUC%extrap: 
Percent of AUC0-inf extrapolated, represented as 
(1 - AUC0-t/AUC0-inf)*100. 
CL/F: 
Apparent total plasma clearance after extravascular 
administration, calculated as Dose/AUC0-inf. 
Cmax: 
Maximum observed concentration. 
Tmax: 
Time to reach Cmax. If the maximum value occurs at more than 
one time point, Tmax is defined as the first time point with this 
value. 
Kel: 
Apparent first-order terminal elimination rate constant calculated 
from a semi-log plot of the plasma concentration versus time 
curve. The parameter will be calculated by linear least-squares 
regression analysis using the maximum number of points in the 
terminal log-linear phase (e.g., three or more non-zero plasma 
concentrations). 
t½: 
Apparent first-order terminal elimination half-life will be 
calculated as 0.693/Kel. 
Vz/F: 
Apparent volume of distribution during the terminal elimination 
phase after extravascular administration, calculated as 
Dose/(AUC0-inf x Kel). 


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No value for Kel, AUC0-inf, CL/F, Vz/F, or t½ will be reported for cases that do not exhibit 
a terminal log-linear phase in the concentration-time profile. 
No PK parameters will be calculated for subjects with 2 or fewer consecutive time points 
with detectable concentrations. 
13.3.3 Analytical Method 
Samples from all subjects receiving active study drug(s) will be assayed even if the subjects 
do not complete the study. Samples collected for potential analysis will be assayed only if 
deemed necessary. 
Samples will be analyzed for plasma BL-8040 and moxifloxacin using validated 
bioanalytical methods.  
13.4 Pharmacodynamic Assessments 
Blood samples for PD analysis (e.g., CD34+ enumeration, RO) will be collected at scheduled 
time points as delineated in the Study Events Flow Chart (Section 6). 
Instructions for blood sampling, collection, processing, and sample shipment will be 
provided separately. 
13.5 Future Research 
Any residual plasma from the PK and/or PD samples will be stored by the Sponsor or 
bioanalytical facility for 5 years after the last dosing and may be used for future analyses 
(e.g., PK, PD). Tubes will be identified with a barcode using an appropriate label. No 
diseases/conditions, deoxyribonucleic acid (DNA), or ribonucleic acid (RNA) will be the 
focus of these analyses. The analyses will only focus on PK, PD, metabolites, and/or 
biomarkers. Samples will not be submitted to a public database. The Sponsor and contract 
research organizations involved in the clinical conduct, bioanalytical analyses and PK and 
statistical analyses of the data will have access to the samples and/or the data that resulted 
from the analysis, if performed. By signing the ICF, subjects agree to the possible future 
analysis of these samples. At any time, the subjects can contact the CRU staff to requested 
destruction of the residual samples after the PK assessments required to meet the objective of 
the study are completed. Any additional research on these samples unspecified by this 
protocol will require approval from the subjects. 


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13.6 Blood Volume Drawn for Study Assessments 
Table 5: Blood Volume During the Study 
Sample Type 
Number of 
Time 
Points 
Approximate 
Volume per Time 
Point * (mL) 
Approximate Sample 
Volume Over Course 
of Study (mL) 
Screening laboratory safety tests 
(including hematology, serum chemistry, 
coagulation, and serology), FSH (for 
postmenopausal female subjects only) 
and serum pregnancy (for female subjects 
only). 
1 
16 
16 
On-study hematology, serum chemistry 
(this includes serum pregnancy for 
female subjects only when scheduled at 
the same time), and coagulation 
9 
16 
144 
Additional on-study CBC samples 
21 
4 
84 
Blood for BL-8040 PK (including 
samples for potential analysis) 
44 
2 
88 
Blood for moxifloxacin PK (including 
samples for potential analysis) 
18 
3 
54 
Blood for PD analysis (CD34+) 
24 
5 
120 
Blood for PD analysis (RO) 
18 
4 
72 
Total Blood Volume (mL)→ 
578 ** 
* 
Represents the largest collection tube that is expected to be used for this sample (a smaller tube may be 
used). 
** 
If additional safety, PK, and/or PD analysis is necessary or if larger collection tubes are required to obtain 
sufficient plasma/serum for analysis, additional blood may be obtained (up to a maximum of 50 mL). 


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14 STATISTICAL CONSIDERATIONS 
Data will be handled and processed according to 
 SOPs, which are written based on 
the principles of GCP. 
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a Statistical Analysis Plan (SAP). The SAP will be prepared by 
 and agreed upon with the Sponsor. This document may modify the plans outlined in 
the protocol; however, any major modifications of the primary endpoints definition and/or its 
analysis will also be reflected in a protocol amendment. Additional statistical analyses other 
than those described in this section may be performed if deemed appropriate. A separate 
Clinical Statistical Analysis Plan, describing the details of the statistical analysis, will be 
prepared by 
 
14.1 Sample Size Determination 
With approximately 40 randomized subjects, it is estimated that at least 26 evaluable subjects 
will have data from all treatment periods. A sample size of 26 evaluable subjects will provide 
more than 90% power to exclude that BL-8040 causes more than a 10 msec QTc effect at 
clinically relevant plasma levels, as shown by the upper bound of the 2-sided 90% CI of the 
model predicted QTc effect (∆∆QTcI) at the observed geometric mean Cmax of BL-8040 in 
the study. This power is estimated approximately using a simple paired t-test. The calculation 
assumes a one-sided 5% significance level, a small underlying effect of 3 msec for BL-8040 
and 0 msec for placebo, and a standard deviation (SD) of ∆QTcI of 8 msec for each 
treatment. Note that this calculation is conservative, since it does not take into account any 
gain in precision due to the use of all data of each subject with the help of a linear mixed 
effects model. The concentration-QTc analysis method is supported by Darpo et al, 2015 and 
Ferber et al, 2015, and consistent with the experiences from 25 recent TQT studies.  
14.1.1 Sample Size Determination for Assay Sensitivity 
Demonstration of assay sensitivity with concentration-QTc will be confirmed by 
demonstrating that the predicted QTc effect (∆∆QTcI) of a single dose of 400 mg 
moxifloxacin exceeds 5 msec, i.e., the lower bound of the 2-sided 90% CI of the predicted 
QTc effect should exceed 5 msec. In a similarly designed, recent crossover study with 
24 healthy subjects (on-file data, 
 the standard error (SE) for the prediction of the QTc 
effect (ΔΔQTcF) of moxifloxacin based on the concentration-QTc analysis was 1.24 msec. 
The SD of ΔQTcF in the referred study was 5.4 msec based on the by-time point analysis. If 
the effect of moxifloxacin is assumed to be 10 msec, the SE of 1.24 msec corresponds to an 
effect size of (10 - 5)/(1.24 x sqrt(24)) = 0.82, where the effect size is the effect assumed 
under the alternative hypothesis divided by the SD of the test-variable. This value should be 
compared to the effect size of 0.59 required to guarantee a power of at least 90% in a paired 
t-test situation with a sample size of 26 evaluable subjects. In other words, based on this 
calculation, a power of at least 90% for 26 evaluable subjects will be obtained as long as the 
variability of ∆QTcI, as measured by its within-subject SD, does not exceed the 7.5 msec 
observed in the referred study (i.e., 139% of the 5.4 msec observed in the referred study 
assuming the ratio of effective sizes is consistent with inverse ratio of within-subject SD). 


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The number also agrees with recent recommendations of the FDA, which propose at least 
20 subjects (Huang et al, 2019). 
14.2 Population for Analyses 
Safety Population: All subjects who received at least one dose of any of the study drugs 
(BL-8040, placebo, or moxifloxacin) will be included in the safety analysis. 
PK Population: All randomized subjects who receive a dose of BL-8040 or moxifloxacin and 
provide at least 1 evaluable PK concentration for BL-8040 or moxifloxacin. 
QT/QTc Population: All subjects in the Safety Population with measurements at Baseline as 
well as on-treatment with at least 1 postdose time point with a valid ΔQTcI value. The 
QT/QTc population will be used for the by-time point and categorical analyses of 
cardiodynamic ECG parameters. 
PK/QTc Population: All subjects who are in both the PK and QT/QTc Populations with at 
least 1 pair of postdose PK and ΔQTcI data from the same time point, as well as subjects in 
the QT/QTc Population who received placebo. The PK/QTc Population will be used for the 
concentration-QTc analysis. PK/QTc population will be defined for BL-8040 and for 
moxifloxacin. 
14.3 Cardiodynamic Analyses 
Details of the cardiodynamic analysis will be provided separately in a SAP. 
14.4 Pharmacokinetic Analyses 
14.4.1 Descriptive Statistics 
The plasma BL-8040 and moxifloxacin concentrations and the PK parameters listed in 
Section 13.3.2 will be summarized using the appropriate descriptive statistics which will be 
fully outlined in the SAP. 
14.5 Pharmacodynamic Analysis 
Details of the PD analysis (e.g., CD34+, RO) will be provided separately and may be 
reported in a separate document outside of the clinical study report (CSR). 
14.6 Safety Analyses 
All safety data will be populated in the individual CRFs. All CRF data will be listed by 
subject in the final report. 
AEs will be coded using the most current version of Medical Dictionary for Regulatory 
Activities (MedDRA®) available at 
 and summarized by treatment for the number of 
subjects reporting the TEAE and the number of TEAEs reported. A by-subject AE data 


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listing including verbatim term, coded term, treatment, severity, and relationship to treatment 
will be provided.  
Safety data including safety ECGs, vital signs assessments, and clinical laboratory results 
(including CBC) will be summarized by treatment and time point of collection. 
Quantitative safety data as well as the difference to baseline, when appropriate, will be 
summarized using the appropriate descriptive statistics. In addition, a shift table describing 
out of normal range shifts will be provided for clinical laboratory results. 
Concomitant medications will be listed by subject and coded using the most current version 
of WHO drug dictionary available at 
 Medical history will be listed by subject. 


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15 STUDY ADMINISTRATION 
15.1 Ethics 
15.1.1 Institutional Review Board 
This protocol will be reviewed by 
 IRB, and the study will not start until the IRB has 
approved the protocol or a modification thereof. The IRB is constituted and operates in 
accordance with the principles and requirements described in the US Code of Federal 
Regulations (21 CFR Part 56). The IRB is compliant to International Council for 
Harmonisation (ICH) guidelines, and may be reached at: 
 
 
15.1.2 Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, US Code of Federal 
Regulations, 21 CFR Parts 50, 56, and 312, the ethical principles set forth in the Declaration 
of Helsinki, GCP, and the ICH harmonized tripartite guideline regarding GCP (E6[R2] Good 
Clinical Practice: Integrated Addendum to E6 [R1], November 2016). 
15.1.3 Subject Information and Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and 
date an ICF summarizing the discussion prior to screening, and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. 
Subjects will be given a copy of their signed ICF. 
15.1.4 
Confidentiality 
All members of the PI’s staff have signed confidentiality agreements with 
. By 
signing this protocol, the PI and 
 staff will regard all information provided by the 
Sponsor and all information obtained during the course of the study as confidential. 
The PI must guarantee the privacy of the subjects taking part in the study. Subjects will be 
identified throughout documentation and evaluation by a unique subject study number. 
Throughout the study, a subject’s source data will only be linked to the Sponsor’s clinical 
study database or documentation via a unique identification number. If subject name appears 
on any study document, it must be redacted before the copy of the documents is supplied to 
the Sponsor. Any information concerning the subjects (clinical notes, identification numbers, 
etc.) must be kept on file by the PI who will ensure that it is revealed only to the Sponsor, 
IRB, or regulatory authorities for the purposes of trial monitoring, auditing or official 
inspections. As required, in the case of an event where medical expenses are the 


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responsibility of the Sponsor, personal information i.e., full name, social security details etc. 
may be released to the Sponsor. Appropriate precautions will be taken to maintain 
confidentiality of medical records and personal information in strictest confidence and in 
accordance with local data protection laws. 
15.2 Termination of the Study 
 reserves the right to terminate the study in the interest of subject welfare. 
The Sponsor reserves the right to suspend or terminate the study at any time. 
15.3 Data Quality Assurance 
Standard operating procedures are available for all activities performed at 
 relevant 
to the quality of this study. Designated personnel of 
 will be responsible for 
implementing and maintaining quality assurance (QA) and quality control systems to ensure 
that the study is conducted, and that data are generated, documented and reported in 
compliance with the study protocol, and GCP requirements as well as applicable regulatory 
requirements and local laws, rules and regulations relating to the conduct of the clinical 
study. 
The CSR will be audited by the QA department and the QA audit certificate will be included 
in the study report. 
All clinical data will undergo a 100% quality control check prior to clinical database lock. 
Edit checks are then performed for appropriate databases as a validation routine using SAS® 
or comparable statistical program to check for missing data, data inconsistencies, data ranges, 
etc. Corrections are made prior to database lock. 
15.4 Direct Access to Source Data/Documents 
 will ensure that the Sponsor, IRB and inspection by domestic and foreign regulatory 
authorities will have direct access to all study-related sites, source data/documents, and 
reports for the purpose of monitoring and auditing (ICH[E6][R2] 5.1.2 & 6.10). In the event 
that other study-related monitoring should be done by other parties, they will be required to 
sign a confidentiality agreement prior to any monitoring and auditing. 
15.5 Drug Supplies, Packaging and Labeling 
The Sponsor will supply sufficient quantities of BL-8040 and BL-8040-matching placebo to 
allow completion of this study. 
 will provide sufficient quantities of sterile 0.45% 
saline (half saline) for injection (use for the reconstitution of BL-8040 and 
BL-8040-matching placebo) and moxifloxacin hydrochloride tablets to allow completion of 
the study. 
 will also provide nizatidine oral solution, cetirizine hydrochloride tablets, 
acetaminophen tablets, and montelukast sodium tablets. Rescue medication will also be 
provided by 
 The lot numbers and expiration dates (where available) of the study 
drugs supplied will be recorded in the final report. 


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Records will be made of the receipt and dispensing of the study drugs supplied. At the 
conclusion of the study, any unused study drugs will be retained by 
 returned to the 
Sponsor or designee, or destroyed, as per Sponsor instructions. Any remaining supplies that 
were purchased by 
 will be destroyed, if appropriate. If no supplies remain, this fact 
will be documented in the pharmacy product accountability records. 
15.6 Data Handling and Record Keeping 
 standard CRFs will be supplied. CRFs are produced, stored electronically, and are 
available to the designated study team members. Each CRF is reviewed and signed by the PI. 
The final signed CRFs are provided to the Sponsor in the format as decided between 
 
and the Sponsor (e.g., compact disc, flashdrive, secure file transfer protocol). This will be 
documented in the data management plan (if applicable).  
All raw data generated in connection with this study, together with the original copy of the 
final report, will be retained by 
 until at least 5 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 5 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period however if required by the applicable regulatory 
requirements or by an agreement with the sponsor. It is the responsibility of the Sponsor to 
inform the PI/Institution as to when these documents no longer need to be retained. 
15.7 Report Format 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common 
Technical Document for the Registration of Pharmaceuticals for Human Use M4 and the 
ICH M2 Expert Working Group), the final report will be written according to the 
ICH E3 Guideline (Structure and Content of Clinical Study Reports).  
15.8 Publication Policy 
All unpublished information given to 
 by the Sponsor shall not be published or 
disclosed to a third party without the prior written consent of the Sponsor. 
The data generated by this study are considered confidential information and the property of 
the Sponsor. This confidential information may be published only in collaboration with 
participating personnel from the Sponsor or upon Sponsor’s written consent to publish the 
article. 


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16 REFERENCES 
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BL-8040 (Motixafortide). BioLineRx Ltd. Investigator’s Brochure. Version 8.0. 23Sep2020. 
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ICH Harmonised Tripartite Guideline. The Clinical Evaluation Of QT/QTc Interval 
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Taubel J, Ferber G, Lorch U, et al. Thorough QT study of the effect of oral moxifloxacin on 
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QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042.