A phase I, single-centre, randomised, single-blinded, placebo-controlled single ascending dose study, followed by an open-label extension, evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of ALX 0651, administered intravenously to healthy male volunteers.

The purpose of the study is to investigate how safe the compound is and how
well the compound is tolerated. The study will also investigate how quickly and
to what extent the compound is absorbed and eliminated from the body (this is
called pharmacokinetics). In addition, the effect of the compound on the body
will be investigated (this is called pharmacodynamics).
This study is not intended to improve your health, but is necessary for the
further development of the compound.

The objectives of this study are to:
* To establish the safety and tolerability of ALX 0651, administered i.v. to
healthy volunteers.
* To investigate the pharmacokinetics of ALX 0651, administered i.v. to healthy
volunteers.
* To investigate the pharmacodynamics of ALX 0651, administered i.v. to healthy
volunteers.
* To establish one or more biologically effective dose (BED) levels and/or the
maximum tolerated dose (MTD) of ALX 0651, administered i.v. to healthy
volunteers.
* To investigate the potential immunogenicity of ALX 0651, administered i.v. to
healthy volunteers.

Design:
a randomized, single-blinded, placebo-controlled, single ascending dose study
with up to 8 cohorts with a maximum of twelve healthy male subjects per cohort
each receiving a single intravenous dose of ALX 0651 or placebo; for the first
and the second cohort sentinel staggering will be applied, two subjects (one
active and one placebo) will be dosed and monitored for 24 h on Day 1 before
the remaining subjects will be dosed; throughout the SAD part of the study one
or more BED levels are likely to be established; the SAD will be followed by a
open-label, single- or multiple-dose extension with up to two cohorts of twelve
subjects receiving intravenous dose(s) of ALX 0651;

in the SD-OLE the (at most two) level(s) * 3 mg/kg that induced the highest
CD34+ count in the SAD part of the study, without significant toxicity, will be
explored, after administration of ALX-0651 at the respective BED level and
determination of WBC count, (at most) 6 subjects that showed a sufficient
pharmacodynamic effect (i.e., WBC * 30 x 109/L) will be assigned to receive
aphaeresis;

when the BED is only established at the 6 mg/kg dose, or could not be
established at all, the MD-OLE will be performed instead of the SD-OLE; In the
MD-OLE ALX 0651 will be administered once-daily for a maximum of 3 consecutive
days, depending on the safety and pharmacodynamic results obtained, the one or
two dose levels * 3 mg/kg that yielded the highest CD34+ count in the SAD part
of the study will be explored, each including 12 subjects, aphaeresis will be
performed in (at most) 2 x 6 subjects achieving * 20 CD34+ cells/µL following
the first or second administration of ALX 0651


SAD and Single dose open label extension, subjects without aphaeresis:
Procedures and assessments:
-Screening and follow-up: clinical laboratory, physical examination,
immunogenicity;12-lead ECG, vital signs; at eligibility screening: medical
history, alcohol breath test and drug screen, HBsAg, anti HCV, anti-HIV 1/2,
weight and height, abdominal ultrasound, clinical laboratory, physical
examination, body weight and alcohol breath test to be repeated upon admission;

-Observation period:
one period in clinic from -17 h up to 48 h after drug administration and an
ambulant visit on Day 14

- Blood sampling:
for pharmacokinetics of ALX-0651: pre-dose and at end of dosing and 0.5, 2, 4,
6, 10, 24, 30 and 48 h post-dose;
for immunogenicity (anti-ALX-0651 antibodies): pre-dose and 312 h post-dose
for flow cytometric analysis (CD34+ cell count): pre-dose and 1, 3, 6, 10, 24,
30, 48 and 312 h post-dose
for white blood cells count: pre-dose and 1, 2, 3, 6, 30 and 312 h post-dose
peripheral blood sample for clonogenic assay (GM-CFC, BFU-E, Mix-CFC): pre-dose
and 1, 3, 6, 10 and 24 h post-dose

-Safety assessments:adverse events: throughout the study; physical exam: 48 h
post-dose; vital signs: pre-dose and at end of dosing, 2, 6, 10, 24 and 48 h
post-dose; 12-lead ECG: pre-dose and 24 and 48 h post-dose; clinical laboratory
(haematology and chemistry): 10, 24 and 48 h post-dose


Single dose open label extension, subjects receiving aphaeresis:
Procedures and assessments
-Screening and follow-up:clinical laboratory, physical examination,
immunogenicity;12-lead ECG, vital signs; at eligibility screening: medical
history, alcohol breath test and drug screen, HBsAg, anti HCV, anti-HIV 1/2,
weight and height, abdominal ultrasound, clinical laboratory, physical
examination, body weight and alcohol breath test to be repeated upon admission

-Observation period:
one period in clinic from -17 h up to 48 h after drug administration and an
ambulant visit on Day 14

- Blood sampling:
for pharmacokinetics of ALX-0651: pre-dose and at end of dosing and 0.5, 2, 24
and 48 h post-dose;
for immunogenicity (anti-ALX-0651 antibodies): pre-dose and 312 h post-dose
for flow cytometric analysis (CD34+ cell count): pre-dose and 1 h post-dose
for white blood cells count: *pre-dose and 1, 2 and 312 h post-dose
peripheral blood sample for clonogenic assay (GM-CFC, BFU-E, Mix-CFC): pre-dose
and 1 h post-dose
for aphaeresis: 3 h post-dose

-Safety assessments: adverse events: throughout the study; physical exam: 24
and 48 h post-dose; vital signs: pre-dose and at end of dosing, 2, 10, 24 and
48 h post-dose; 12-lead ECG: pre-dose and 24 and 48 h post-dose; clinical
laboratory (haematology and chemistry): 10, 24 and 48 h post-dose


Multiple dose open label extension, subjects receiving aphaeresis on Day 2:
Procedures and assessments
-Screening and follow-up:clinical laboratory, physical examination,
immunogenicity, 12-lead ECG, vital signs; at eligibility screening: medical
history, alcohol breath test and drug screen, HBsAg, anti HCV, anti-HIV 1/2,
weight and height, abdominal ultrasound, ; clinical laboratory, physical
examination, body weight and alcohol breath test to be repeated upon admission

-Observation period:
one period in clinic from -17 h before drug administration on Day 1 up to 48 h
after drug administration on Day 2 and an ambulant visit on Day 14

-Blood sampling:
for pharmacokinetics of ALX-0651: pre-dose and at end of dosing and 0.5, 2, 4,
6 and 10 h post-dose on Day 1, pre-dose and at end of dosing and 0.5, 2, 24 and
48 h post-dose on Day 2
for immunogenicity (anti-ALX-0651 antibodies): pre-dose on Day 1 and 288 h
post-dose on Day 2
for flow cytometric analysis (CD34+ cell count): pre-dose and 1, 3, 6 and 10 on
Day 1 and pre-dose and 1 h post-dose on Day 2
for white blood cells count: pre-dose and 1, 2, 3 and 6 h post-dose on Day 1
and 1, 2 and 288 h post-dose on Day 2
peripheral blood sample for clonogenic assay (GM-CFC, BFU-E, Mix-CFC): pre-dose
and 1 h post-dose on Day 2
for aphaeresis: 3 h post-dose on Day 2

-Safety assessments: adverse events: throughout the study; physical exam:
pre-dose, 24 and 48 h post-dose on Day 2; weight: pre-dose on Day 2; vital
signs: pre-dose and at end of dosing, 2, 6, and 10 h post-dose on Day 1 and
pre-dose, at end of dosing, 2, 10, 24 and 48 h post-dose on Day 2; 12-lead ECG:
pre-dose on Day 1 and pre-dose and 24 and 48 h post-dose on Day 2; clinical
laboratory (haematology and chemistry): 10 h post-dose on Day 1 and pre-dose,
10, 24 and 48 h post-dose on Day 2


Multiple dose open label extension, subjects receiving aphaeresis on Day 3
Procedures and assessments
-Screening and follow-up:clinical laboratory, physical examination,
immunogenicity; 12-lead ECG, vital signs; at eligibility screening: medical
history, alcohol breath test and drug screen, HBsAg, anti HCV, anti-HIV 1/2,
weight and height, abdominal ultrasound, clinical laboratory, physical
examination, body weight and alcohol breath test to be repeated upon admission;

-Observation period:
one period in clinic from -17 h before drug administration on Day 1 up to 48 h
after drug administration on Day 3 and an ambulant visit on Day 14

-Blood sampling:
for pharmacokinetics of ALX-0651: pre-dose and at end of dosing and 0.5, 2, 4,
6 and 10 h post-dose on Day 1, pre-dose and at end of dosing at Day 2, pre-dose
and at end of dosing and 0.5, 2, 24 and 48 h post-dose on Day 3
for immunogenicity (anti-ALX-0651 antibodies): pre-dose on Day 1 and 264 h
post-dose on Day 3
for flow cytometric analysis (CD34+ cell count): pre-dose and 1, 3, 6 and 10 on
Day 1 and pre-dose, 1, 3, 6 and 10 h post-dose on Day 2, pre-dose and 1 h
post-dose on Day 3
for white blood cells count: pre-dose and 1, 2, 3 and 6 h post-dose on Day 1
and 1, 2, 3 and 6 h post-dose on Day 2, 1, 2 and 264 h post-dose on Day 3
peripheral blood sample for clonogenic assay (GM-CFC, BFU-E, Mix-CFC): pre-dose
and 1, 3 and 6 h post-dose on Day 2
for aphaeresis: 3 h post-dose on Day 3

-Safety assessments: adverse events: throughout the study; physical exam:
pre-dose on Day 2, pre-dose, 24 and 48 h post-dose on Day 3; weight: pre-dose
on Days 2 and 3; vital signs: pre-dose and at end of dosing, 2, 6, and 10 h
post-dose on Day 1 and pre-dose, at end of dosing, 2, 6 and 10 h post-dose on
Day 2, pre-dose, at end of dosing, 2, 10, 24 and 48 h post-dose on Day 3;
12-lead ECG: pre-dose on Days 1 and 2 and pre-dose and 24 and 48 h post-dose on
Day 3; clinical laboratory (haematology and chemistry): 10 h post-dose on Day 1
and pre-dose and 10 h post-dose on Day 2 and pre-dose,10, 24 and 48 h post-dose
on Day 3


Multiple dose open label extension, without aphaeresis
Procedures and assessments
-Screening and follow-up:clinical laboratory, physical examination,
immunogenicity 12-lead ECG, vital signs; at eligibility screening: medical
history, alcohol breath test and drug screen, HBsAg, anti HCV, anti-HIV 1/2,
weight and height, abdominal ultrasound ; clinical laboratory, physical
examination, body weight and alcohol breath test to be repeated upon admission;
at follow-up only: immunogenicity

-Observation period:
one period in clinic from -17 h before drug administration on Day 1 up to 48 h
after drug administration on Day 3 and ambulant visit on Day 14

-Blood sampling:
for pharmacokinetics of ALX-0651: pre-dose and at end of dosing and 0.5, 2, 4,
6 and 10 h post-dose on Day 1, pre-dose and at end of dosing at Day 2, pre-dose
and at end of dosing and 0.5, 2, 4, 6, 10, 24, 30 and 48 h post-dose on Day 3
for immunogenicity (anti-ALX-0651 antibodies): pre-dose on Day 1 and 264 h
post-dose on Day 3
for flow cytometric analysis (CD34+ cell count): pre-dose and 1, 3, 6 and 10 on
Day 1 and pre-dose, 1, 3, 6 and 10 h post-dose on Day 2, pre-dose and 1, 3,
6, 10, 24, 30, 48 and 264 h post-dose on Day 3
for white blood cells count: pre-dose and 1, 2, 3 and 6 h post-dose on Day 1
and 1, 2, 3 and 6 h post-dose on Day 2, 1, 2, 3, 6, 30 and 264 h post-dose on
Day 3
peripheral blood sample for clonogenic assay (GM-CFC, BFU-E, Mix-CFC):
pre-dose, 1, 3 and 6 h post-dose on Day 2

-Safety assessments: adverse events: throughout the study; physical exam:
pre-dose on Day 2, pre-dose and 48 h post-dose on Day 3; weight: pre-dose on
Days 2 and 3; vital signs: pre-dose and at end of dosing, 2, 6, and 10 h
post-dose on Day 1 and pre-dose, at end of dosing, 2, 6 and 10 h post-dose on
Day 2, pre-dose, at end of dosing, 2, 10, 24 and 48 h post-dose on Day 3;
12-lead ECG: pre-dose on Days 1 and 2 and pre-dose and 24 and 48 h post-dose on
Day 3; clinical laboratory (haematology and chemistry): 10 h post-dose on Day 1
and pre-dose and 10 h post-dose on Day 2 and pre-dose,10, 24 and 48 h post-dose
on Day 3


Bioanalysis:
-analysis of plasma ALX-0651 samples using a validated method by sponsor
-flow cytometric analysis (CD34+ cell count) using a validated method by PRA
-clonogenic assays using a validated method by sponsor
-analysis of anti-ALX-0651 antibodies samples using a validated method by
sponsor

ALX-0651 as bolus injection for first dose level, rest by iv

procedures: pain, light bleeding, heamatoma, possibility an infection.
see E9