A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE ASCENDING DOSE TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF LEO 158968 IN HEALTHY SUBJECTS

LEO 158968 is a new compound that may potentially be used for the treatment of
several inflammatory diseases. LEO 158968 is a monoclonal antibody and is a
*custom-made* protein that has been assembled in a laboratory. This can attach
to proteins that are on the surface of body cells or that move in the blood.
LEO 158968 has been developed to block signaling pathways of three IL-1 family
members that have important roles in several inflammatory diseases. IL-1 is a
substance in the body which is involved in normal inflammatory and immune
responses.

In this study we will investigate how safe the new compound LEO 158968 is and
how well it is tolerated when it is used by healthy subjects.

We also investigate how quickly and to what extent LEO 158968 is distributed
and eliminated from the body. In addition, we look at the effect of LEO 158968
on your immune cells and specific markers in the blood.

We compare the effects of LEO 158968 with the effects of a placebo.

LEO 158968 has not been given to humans before. It has been extensively tested
in the laboratory and on animals. LEO 158968 will be tested at various dose
levels.

Part A:
The study lasts a maximum of 4 months from the screening to the follow-up check.
For the research it is necessary to stay in the research center for 1 period of
6 days.

Day 1 is the day on which the study drug is received. We expect the volunteers
to be in the research center one day before taking the research drug. In that
case, you must report between 9:30 a.m. and 2:00 p.m. You will be informed
about the exact time. The volunteers leave the study center on Day 5 (after 5
nights) of the study. After the stay in the research center there will be 5
short visits. These short visits take place on Days 8, 15, 29, 57 and 85.

LEO 158968 or placebo is given as an intravenous infusion or a subcutaneous
injection.

Whether one receives LEO 158968 or placebo is determined by lottery. A maximum
of 6 subjects per group receive LEO 158968 and 2 subjects receive placebo.
Neither the volunteer nor the investigators know whether one is receiving LEO
158968 or placebo; We call this a double-blind study.

Part B:
The examination lasts a maximum of 5 months from the inspection to the
follow-up check.

For the research it is necessary to stay in the research center for 4 periods.
A 10-day period, 1 6-day period and 2 3-day periods.

Day 1 is the day on which the volunteer receives the research drug. We expect
the volunteers at the research center one day before taking the research drug.
You must report between 9:30 a.m. and 2:00 p.m. You will be informed about the
exact time. The entry time can be adjusted. If this happens, you will be
informed in advance. The volunteer leaves the study center on Day 9 of the
study. After the stay in the research center one will come back for 3 extra
stays. These stays take place from Day 14 to Day 16 (2 nights), from Day 21 to
Day 23 (2 nights) and from Day 28 to Day 33 (5 nights). After your stays at the
research center there will be 7 short visits to the research center. These
short visits take place on Days 36, 43, 57, 71, 85, 99 and 113.

LEO 158968 or placebo is given as a subcutaneous (subcutaneous) injection.

SAD part:
Group A1, Day 1, LEO 158968 5 mg or placebo, once, Intravenous infusion
Group A2, Day 1, LEO 158968 10 mg or less, or placebo, once, Intravenous
infusion
Group A3, Day 1, LEO 158968 15 mg or less, or placebo, once, Intravenous
infusion
Group A4, Day 1, LEO 158968 45 mg or less, or placebo, once, Intravenous
infusion
Group A5, Day 1, LEO 158968 85 mg or less, or placebo, once, Intravenous
infusion
Group A6, Day 1, LEO 158968 85 mg or less, or placebo, once, Subcutaneous
injection
Group A7, Day 1, LEO 158968 225 mg or less, or placebo, once, Intravenous
infusion
Group A8, Day 1, LEO 158968 450 mg or less, or placebo, once, Subcutaneous
injection
Group A9, Day 1, LEO 158968 900 mg or less, or placebo, once, Subcutaneous
injection
Group A10, Day 1, LEO 158968 1350 mg or less, or placebo, once, Subcutaneous
injection
Group A11, Day 1, LEO 158968 250mg or less, or placebo, once, Intravenous
infusion
Group A12, Day 1, LEO 158968 500mg or less, or placebo, once, Intravenous
infusion

MAD part:
Group B1, Day 1, 8, 15, 22 and 29, LEO 158968 150 mg or less, or placebo, once
weekly, Subcutaneous injection
Group B2, Days 1, 8, 15, 22 and 29, LEO 158968 300 mg or less, or placebo, once
weekly, Subcutaneous injection
Group B3, Day 1, 8, 15, 22 and 29, LEO 158968 600 mg or less, or placebo, once
weekly, Subcutaneous injection

Blood draw
Blood draws may hurt or cause bruising. Using an indwelling cannula can
sometimes cause inflammation, swelling, hardening of the artery, or blood
clotting and bleeding around the puncture site. In some individuals, a blood
draw can sometimes cause paleness, nausea, sweating, slow heart rate, or drop
in blood pressure with dizziness or fainting.

All in all, we take approximately 364 milliliters (ml) with an intravenous
infusion or 314 milliliters (ml) with an injection under the skin from the
volunteer from the examination to the follow-up check for the SAD part or 566
milliliters for the MAD part . This amount does not cause any problems in
adults. If the researcher considers this necessary to ensure the safety of the
subject, additional samples can be taken for any additional testing. If this
happens, the total amount of blood drawn may be more than the amount indicated
above.

ECG
To make a heart film, electrodes are placed on the arms, chest and legs.
Prolonged use of these electrodes may cause skin irritation.

Coronavirus test
Samples for the coronavirus test will be taken with cotton swabs at the back of
the nose and throat. Taking the samples only takes a few seconds, but can cause
discomfort and discomfort. Taking a sample from the back of the throat may
result in gagging. When the sample is taken at the back of the nose, one may
experience a stinging sensation and the eyes may water.