A two-part, single dose, randomized, single-blinded, placebo controlled, phase I study to assess the safety and pharmacokinetics of oral MT1980 in healthy volunteers when dosed in the fasted state

MT1980 is being developed as a treatment for neuroinflammation (an inflammatory
response in the brain and/or spinal cord). Much research has focused on the
central role of neuroinflammation in the pathogenesis of many conditions
relating to the CNS, including eg, traumatic brain injury, stroke, Alzheimer's
disease, post-operative cognitive decline (POCD)/perioperative neurocognitive
disorder, and now even long-term cognitive side effects from severe acute
respiratory syndrome corona virus 2 (SARS-CoV-2). Current anti-inflammatories
do not easily cross the blood-brain barrier from the systemic circulation to
the brain, making neuroinflammation a difficult condition to treat.

In this study we will investigate how safe the new compound MT1980 is and how
well it is tolerated when it is used by healthy participants.

We also investigate how quickly and to what extent MT1980 is absorbed,
transported, and eliminated from the body. In addition, we look at the amount
of drug in cerebrospinal fluid (CSF, the liquid surrounding the brain and the
spinal cord) and in blood plasma after MT1980 intake.

We compare the effects and safety of MT1980 with the effects of a placebo.

The study will take a maximum of about 4.5 weeks from the screening until the
follow-up visit.

Screening -> Between Day -21 and Day -1

Treatment Part 1 and 2 - Arrival -> Day -1
Treatment Part 1 and 2 - In-house stay -> Day -1 up to Day 4
Treatment Part 1 and 2 - Departure -> Day 4

Follow-up call -> Between Day 7 and Day 9

Either MT1980 or placebo as oral capsules with 240 milliliters (mL) of (tap)
water.

Part 1: once 140 mg MT1980 or placebo

Part 2: once between 25 mg and 250 mg MT1980 based on the results from Part 1
or placebo

Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) can sometimes lead to inflammation,
swelling, hardening of the vein, blood clotting, and bleeding in the
environment (bruising) of the puncture site. In some individuals, a blood draw
can sometimes cause pallor, nausea, sweating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take about 82 milliliters (mL) of blood from screening to
follow-up. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken each time. If the
investigator thinks it is necessary for the safety of a participant, extra
samples might be taken for possible additional testing. If this happens, the
total amount of blood drawn may be more than the amount indicated above.

Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation (rash and itching).

Collection of CSF via lumbar puncture

Procedure
The collection of up to 2 mL CSF is done via lumbar puncture by placing a
needle into the lower back, where there is the CSF. CSF will be collected at 2
timepoints (Part 1) or 1 timepoint (Part 2), after administration of the study
compound. The anesthesiologist will apply numbing medication to minimize any
pain or discomfort from the needle. If needed, a syringe may be used to gently
aspirate CSF.

Risks during the procedure
CSF collection via lumbar puncture may cause pain (particularly in the back),
nausea (feeling sick), headache, discomfort, bruising, stiffness, fainting,
allergic reactions, and, rarely, an infection at the site of the needle
insertion. Occasionally, during needle insertion, a nerve in the spinal cord
(spinal nerve) might be touched, causing pain to spread to the buttock or leg.
This usually lasts only a short time. Rarely, participants may experience
bleeding into the spinal canal, or a spinal canal nerve damage.

Meningitis (an acute inflammation of the protective membranes covering the
brain and spinal cord, known collectively as the meninges) is a rare potential
side effect of CSF collection. This could cause headache, photophobia (abnormal
intolerance to light), neck stiffness, and pyrexia (increase in body
temperature). If this happens, routine standard of care for the management of
suspected bacterial meningitis must be implemented (for example, antibiotic
treatment).

What is allowed during the procedure
Subjects will be asked to lie down on their back with limited movement for
approximately 1 hour after the lumbar puncture. If they develop a headache,
they will be encouraged to lie in a comfortable position.

Risks after the procedure
Headache after lumbar puncture often occurs, especially in younger people, and
can be accompanied by dizziness, nausea, and ringing in the ears (tinnitus).
The symptoms can persist for several days up to 2 weeks after removal of the
needle. The cause of the headache is probably the leakage of CSF. The headache
is usually in the front and back of the head and is less when one lies down.
The headache usually goes away on its own within 7 days and can be reduced with
rehydration, paracetamol, and caffeine. In severe cases, it may be decided to
close the hole with an injection of their own blood at the site where the
needle was inserted in the back. This treatment is called *blood patch*.

Coronavirus test
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause them to gag. When the sample is taken from the back of the
nose, they may experience a stinging sensation and the eyes may become watery.