A 4-part Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of M254 in healthy volunteers and in patients with immune thrombocytopenic purpura.

M254 is a new compound that may eventually be used for the treatment of primary
immune thrombocytopenia Purpura (ITP). ITP is an autoimmune disease
characterized by decreased numbers of platelets in the blood. ITP affects both
children and adults. Symptoms of ITP include petechia (very small red or purple
spots on the skin), purpura (red or purple discolored spots on the skin caused
by bleeding under the skin), bruising, and overt bleeding. To stop or prevent
bleeding, ITP patients can be treated with intravenous antibodies, so called
immunoglobulin G (IVIg). IVIg is a therapeutic blood product prepared from
pooled blood plasma of 3,000 to 60,000 healthy donors. IVIg has been used for
treatment of a variety of acute and chronic autoimmune and systemic
inflammatory diseases for decades, including ITP.

Due to treatment with IVIg, the number of platelets in the blood will be
increased. However, high doses and long infusion times are required for
efficacy.

M254 is derived from commercially available IVIg. In M254, the level of
sialylation of the IgG subtypes present has been increased via enzymatic
reactions. Literature suggests that the anti-inflammatory properties of IVIg
may be dependent on the level of sialic acid. Therefore, due to the higher
level of sialylation of IgG antibodies in M254, it is expected that M254 has
potentially greater effectiveness when compared to IVIg.

The purpose of this study is to investigate how safe the new compound M254 is
and how well it is tolerated when it is administered to healthy volunteers and
patients with immune thrombocytopenia (ITP). M254 has not been administered to
humans before. It has been previously tested in the laboratory and on animals.

It will also be investigated how quickly and to what extent M254 is eliminated
from the body (this is called pharmacokinetics [PK]). In addition, the effect
of M254 on the body will be investigated (this is called pharmacodynamics
[PD]).

This study will be performed in approximately 25 healthy male or female
volunteers and approximately 55 patients with ITP. The study will be performed
in 4 parts, Part A, Part B, Part C and Part D.

Part A has been completed. Twenty five healthy male or female volunteers were
enrolled.

In Part A of the study, the safety, tolerability and PK of a single dose of
M254 will be compared to placebo. M254 will be tested at various dose levels. A
placebo contains no active ingredient. The safety and tolerability of M254 can
be studied better, when some subjects in the trial receive placebo in an
identical situation for comparison.

Part B of the study will consist of 4 tot 6 groups, each with 2 patients with
ITP. After completion of Part B, patients are also allowed to participate in
Part D of the study.

In Part B, the safety, tolerability, PK and PD of M254 will be compared to that
of a similar compound, IVIg. IVIg has been the standard treatment of ITP for
decades. In addition, the PK and PD of different doses of M254 will be
evaluated.

Part C of the study will consist of 2 groups, each with 10 patients with ITP.
After completion of Part C, patients are also allowed to participate in Part D
of this study.

In Part C of the study, the safety, tolerability, PK and PD of up to 2 dose
levels of M254 will be compared to that of IVIg.

Part D includes 15 to 34 patients with ITP. Patients who have participated in
Part B or Part C may be offered to participate in Part D

In Part D of the study the safety, tolerability, PK and PD of 3 to 4 doses of
M254 will be evaluated.

Part A: Participation from screening until follow-up is in total about 8 weeks.
M254 or placebo will be given as an intravenous infusion (solution of the
compound that will be administered directly in a blood vessel). The infusion
duration will depend on the dose to be administered. In general, the infusion
duration will be between approximately 6 minutes and 3.5 hours, depending on
the dose received
.
Part B: Participation from screening until follow-up is in total about 8 weeks.
All patients receive a single dose of M254 which is followed 4 weeks later by a
single dose with IVIg. No placebo will be administered in this part of the
study. M254 and IVIg will be given as an intravenous infusion (solution of the
drug administered directly into a blood vessel). The infusion duration will
depend on the amount of M254 to be administered (up to 4 hours for M254). The
infusion of IVIg may take up to 5 hours and 30 minutes depending on the body
weight.

Part C: Participation from screening until follow-up is in total about 12 to 20
weeks.
All patients receive a single dose of M254 and a single dose of IVIg. There is
approximately 4 weeks between the administration of M254 and IVIg. The group
in which the patients participate and thus in which order they receive M254 or
IVIg is determined by chance. No placebo will be administered in this part of
the study. M254 and IVIg will be given as an intravenous infusion (solution of
the drug administered directly into a blood vessel). The infusion duration will
depend on the amount of M254 to be administered (up to 4 hours for M254). The
infusion of IVIg may take up to 5 hours and 30 minutes depending on the body
weight.

Part D: Participation from screening until follow-up is in total about 12 to 14
weeks.

If one has not participated in Part B or C, the volunteer receives 4 times a
dose of M254 (Group 1). If one has already participated in Part B or C, one
receives 3 times a dose of M254 (Group 2). There is approximately 2 weeks
between each dose with M254. No placebo will be administered in this part of
the study. M254 will be given as an intravenous infusion (solution of the drug
administered directly into a blood vessel). The infusion duration will depend
on the amount of M254 to be administered. (up to 4 hours).

Part A:
Group 1; Day 1; M254 3 mg / kg or placebo; once; Intravenous infusion
Group 2; Day 1; M254 10 mg / kg or placebo, once, intravenous infusion
Group 3; Day 1; M254 30 mg / kg or placebo, once, intravenous infusion
Group 4; Day 1; M254 60 mg / kg or placebo, once, intravenous infusion
Group 5; Day 1; M254 120 mg / kg or placebo, once; intravenous infusion
Group 6; Day 1; M254 250 mg / kg or placebo, once; intravenous infusion
Group 7c; Day 1; M254 NTB mg / kg or placebo, once; intravenous infusion
Group 8c; Day 1; M254 NTB mg / kg or placebo, once; Intravenous infusion

Part B:
Group 1; Day 1; M254 60 mg / kgb; once; intravenous infusion
Group 1; Day 29; Privigen 1000 mg / kg; once, intravenous infusion
Group 2; Day 1; M254 120 mg / kg; once; intravenous infusion
Group 2; Day 29; Privigen 1000 mg / kg; once; intravenous infusion
Group 3; Day 1 M254 250 mg / kg; once; intravenous infusion
Group 3; Day 29; Privigen 1000 mg / kg; once; intravenous infusion
Group 4; Day 1; M254 500 mg / kg; once; intravenous infusion
Group 4; Day 29; Privigen 1000 mg / kg; once; intravenous infusion
Group 5; Day 1; M254 TBD mg / kg; once; intravenous infusion
Group 5; Day 29; Privigen 1000 mg / kg; once; intravenous infusion
Group 6; Day 1; M254 TBD mg / kg; once; intravenous infusion
Group 6; Day 29; Privigen 1000 mg / kg; once; intravenous infusion


Part C:
Two different amounts of M254 will be used based on the results of Parts A and
B of this study and will not exceed 500 mg/kg. Patients will receive either the
low amount or the high amount of M254 depending on which amount is being tested
when entering the study.

Part D:
Group 1 Day 1; M254 (NTB mg/kgb); once, Intravenous Infusion
Group 1 Day 15; M254 (NTB mg/kg); once, Intravenous Infusion
Group 1 Day 29; M254 (NTB mg/kg); once, Intravenous Infusion
Group 1 Day 43; M254 (NTB mg/kg); once, Intravenous Infusion

Group 2 Day 1; M254 (NTB mg/kg); once, Intravenous Infusion
Group 2 Day 15; M254 (NTB mg/kg); once, Intravenous Infusion
Group 2 Day 29; M254 (NTB mg/kg); once, Intravenous Infusion

Pain, minor bleedings, bruises and possibly an infection.