A randomized, parallel-group clinical pharmacology study to assess the pharmacokinetics and pharmacodynamics of Tysabri® in healthy volunteers

The Sponsor is developing a compound (PB006) similar to Tysabri. In preparation
for medical-scientific studies to confirm the similarity of the two compounds,
the Sponsor wants to study the effect of different doses of Tysabri on the
body.

Tysabri is a drug approved in Europe and the USA for the treatment of Multiple
Sclerosis (MS) and in the USA also for the treatment of Crohn*s Disease. MS
causes inflammation in the brain that damages the nerve cells. Symptoms of MS
can include: walking problems, numbness in the face, arms or legs, problems
seeing things, tiredness, feeling off-balance or light headed, bladder and
bowel problems, difficulty in thinking and concentrating, depression, acute or
chronic pain, sexual problems, and stiffness and muscle spasms.

The active ingredient of Tysabri is natalizumab which is a monoclonal antibody.
These antibodies work by binding to proteins in the body so that the harmful
effect of that protein is removed. Tysabri stops the cells that cause
inflammation from going into the brain. This reduces nerve damage caused by MS.

The study will be performed in up to 36 volunteers who will participate in 16
visits, of which one will be a confinement of 4 days.

The purpose of this study is to investigate how quickly and to what extent
different doses of EU­approved Tysabri® are absorbed and eliminated from the
body (this is called pharmacokinetics) and how the body responds to different
doses of Tysabri (this is called pharmacodynamics) and. In addition, the study
will assess the safety profile of Tysabri at different doses.

The actual study will consist of 1 period during in which the volunteer will
stay in the research center in Groningen location UMCG for 4 days (3 nights).
Day 1 is the day of administration of the study compound. The volunteer is
expected at the research center at 14:00 h in the afternoon prior to the day of
administration of the study compound. The volunteer will leave the research
center on Day 3 of the study.This will be followed by 11 days during which the
volunteer will visit the research center for a short visit. These short visits
will take place on Day 5, 8, 15, 22, 29, 36, 43, 57, 71, 78, and 85.

During the volunteers last short visit (Day 85) their health will be checked
for the last time. An additional follow-up visit is planned between Day 162 and
176 to monitor for any signs or symptoms that may indicate progressive
multifocal leukoencephalopathy (PML).

Tysabri will be given as an intravenous infusion (solution of the compound that
will be administered directly in a blood vessel) over 60 minutes. The volunteer
will receive one of 3 doses of Tysabri (1, 3, or 6 mg/kg body weight).

The following side effects have been reported in medical-­research studies:
urinary tract infection, sore throat and runny or blocked up nose, shivering,
itchy rash (hives), headache, dizziness, feeling sick (nausea), being sick
(vomiting), joint pain, fever, tiredness.

Drawing blood and insertion of the indwelling cannula may be painful or cause
some bruising.A small amount of blood will be drawn during the screening.

To monitor your heart rate, electrodes (small, plastic patches) will be pasted
at specific locations on the chest and abdomen. Prolonged use of these
electrodes can cause skin irritation (rash and itching).