Single center, randomized, double-blind, 3-period, 3 treatments, 3 way crossover pharmacokinetics (PK)/pharmacodynamics (PD) trial to assess PK, PD, safety and tolerability of MYL-1401H after single subcutaneous injection at one dose level (2 mg) comparing to an EU and US marketed drug product (NEULASTA®) in healthy volunteers.

Neulasta® is a drug registered for treatment of a shortage of white blood cells
in order to prevent infections. It is used mostly for cancer patients to treat
the side effects of chemotherapy. Neulasta® is the brand name; the active
ingredient is called pegfilgrastim. This is a protein which is very similar to
the human version *granulocyte colony stimulating factor* (also known as GCSF
or filgrastim). GCSF is present in the human body by nature. Therefore,
Neulasta® is called a *biological*. The difference between naturally occurring
GCSF and pegfilgrastim is the attachment of a large chain of molecules (a
polymer) to the protein. This makes the protein stay longer in the body so
patients need to receive drug less often to achieve the same effect. MYL-1401H
is a new pegfilgrastim strongly resembling Neulasta®. Both Neulasta® and
MYL-1401H are produced with the help of bacteria which have received a human
gene which makes them able to produce this protein. This is the first time that
the MYL-1401H compound is being given to humans.

In this study the volunteers will receive MYL-1401H, Neulasta® EU (EU-licensed
product) and Neulasta® US (US licensed product) on three separate occasions.

The purpose of the study is to investigate how quickly and to what extent
MYL-1401H is absorbed and eliminated from the body (this is called
pharmacokinetics) as compared to Neulasta® EU and US. It will also be
investigated what the effect is of MYL-1401H on blood cells as compared to the
two Neulasta® versions. Finally, it will be investigated to what extent
MYL-1401H is tolerated.

This study is a single center, randomized, double-blind, 3-period, 3
treatments, 3 way crossover pharmacokinetics (PK)/pharmacodynamics (PD) trial
to assess PK, PD, safety and tolerability of MYL-1401H after single
subcutaneous injection at one dose level (2 mg) comparing to an EU and US
marketed drug product (NEULASTA®) in healthy volunteers.

The actual study will consist of 3 periods. In each period the volunteer will
stay in the clinical research center in Groningen for 7 days (6 nights)
followed by a period of 17 days during which they will visit the clinical
research center in Groningen on 7 occasions (on Day 6, Day 7, Day 8, Day 9, Day
12, Day 15 and Day 22 of each period). After the 3rd and last period, the
post-study screening will take place on Day 29. The duration of the different
periods is at least 4 weeks.

At the beginning of each period (Day 1) the volunteer will receive MYL-1401H,
Neulasta® EU or Neulasta® US after breakfast in the morning. They will receive
one injection of 0.2 mL under the skin of the abdomen. After drug
administration they will be required to remain in a lying position for at least
4 hours. During this period, lying on the stomach is not allowed.

Repeated single dose of 2 mg study drug delivered by 0.2 ml subcutaneous (SC)
injections.

During the investigation, various assessments will be done that can be
experienced as more or less stressfull.

Blood draw, SC injections and the ECG can be experienced as stressfull in this
respect.