Soon a clinical trial will start at ICON with an investigational compound that may potentially be used for the treatment of neurodegenerative diseases. Neurodegenerative diseases are diseases where brain cells (neurons) stop working or die. Examples of this type of diseases are Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and ALS (Amyotrophic Lateral Sclerosis). There is currently no cure for these diseases and they get worse over time. Inflammation in the brain could be a contributing factor. The study compound is a compound that can reduce inflammation in the brain and could benefit people with neurodegenerative diseases.

In this trial, we investigate how safe the study compound is and how well it is tolerated when it is administered to healthy participants.

Furthermore, we investigate how quickly and to what extent the compound is absorbed, transported, and eliminated from the body.

During this study cerebrospinal fluid (CSF) samples will be collected via lumbar puncture twice: once before administration of the study compound and once afterwards. We will measure the amount of study compound and other compounds in the CSF. CSF is the liquid surrounding the brain and the spinal cord. It is produced continuously and in large quantities, which makes it safe to take small amounts of CSF. To collect CSF from the spinal cord, a very fine needle is inserted between two vertebrae in your lower back. The procedure will be carried out by trained medical personnel using a technique that minimizes risks and you will be monitored closely. Before the CSF collection, you will undergo tests to check if it is safe to carry out the CSF collection (for example blood test and neurological examination).

We compare the effects of the compound with the effects of a placebo. A placebo is a compound without any active ingredient. Whether you receive the study compound or placebo will be determined by chance. Please note that when the term ‘study compound’ is used in this document, we mean the new compound, placebo, or both.

The study compound has been tested in the laboratory and on animals. The first part of this study in humans has been completed and we are currently recruiting for the second part.

This trial is not intended to improve your health but is necessary for the further development of this compound. The trial has been approved by the Independent Ethics Committee (METC).

This trial will be executed in healthy male and female participants. You can participate only once in this trial.

To check if you are eligible to participate a medical screening will take place before the start of the trial. Depending on availability, this can be performed in Groningen or Utrecht. This screening will take place within 4 weeks before the start of the clinical trial.

For group B7 to B9, the trial consists of 4 periods and 7 short visits. In total you will visit the research center 12 times:

* once for the screening;
* once for a stay in the research center of 6 days (5 nights);
* once for a stay in the research center of 4 days (3 nights);
* once for a stay in the research center of 5 days (4 nights);
* once for a stay in the research center of 2 days (1 night);
* 7 visits to the research center, of which the last one is the final follow-up visit.

You will receive the study compound or placebo three times in total. You will be given the study compound or placebo as intravenous infusion (solution of the compound that will be administered directly in a blood vessel), which will take around 60 minutes.

During the trial, blood will regularly be drawn and urine will be collected. Prior to screening, (each) admission, and the follow-up, you have to stay fasted for 4 hours. You can only drink water prior to your visit. This means that we will ask you to fast prior to any participation in the trial. Before any study related procedures, you will sign the informed consent form. After the screening it will be announced whether you can participate.

On the days you will receive the compound you will receive standardized meals (a standard composition and amount). This is less standardized on the other days.

Consumption of medication, alcohol, and tobacco- / nicotine-containing products are not allowed during the your stay in the research facility. Also, before the start of the trial and when you are not staying in the research facility, there could be restrictions for these products (poppy seeds, alcohol, and tobacco- / nicotine-containing products). We will explain more about this during a phone conversation. Use of decaffeinated coffee and (herbal) teas without caffeine (also called theine) is allowed.

All potential medicines can cause side effects.

The compound has been studied in the laboratory and in animals. Based on the way this study compound works, the following side effects could occur:

• Infections of the skin that may require medical intervention such as the use of an antibiotic or antifungal.
• Infection of the central nervous system, such as:
  • Meningitis is an infection associated with inflammation of the fluid and membranes that cover the brain and spinal cord.
  • Encephalitis, an inflammatory reaction in the brain that could be triggered by infection from a virus or bacteria.
• Temporary change to your mood, memory and learning ability.
• Allergic reaction.
• Skin symptoms, such as itching or a rash.

In Part A, healthy subjects received the study compound as single infusion. Preliminary findings are written in the informed consent form, which you will receive before your screening visit.

You should take into account that side effects may occur that are still unknown. In addition to unknown side effects, there is a (small) chance that an allergic reaction will occur. This can be caused by the study compound or other ingredients that are used to prepare the formulation. During the study, you will be under strict medical supervision. The doctors and investigators of ICON are always well-informed about the compound being studied. With this knowledge they can estimate the effects and side effects reasonably well.

The lumbar puncture procedure could cause pain, nausea (feeling sick), headache, discomfort, bruising, stiffness, bleeding, and, rarely, an infection. Occasionally, during needle insertion, a 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 spinal canal nerve damage. Headache after lumbar puncture can be accompanied by dizziness, nausea and ringing in the ears (tinnitus). If you develop a headache, you will be encouraged to lie down in a comfortable position. In most cases headache can be alleviated with bed rest, drinking enough water, and simple painkillers if needed. Most headaches last for several hours to two days; in extremely rare cases, headaches persisting for a full week have been reported. If the headache does not go away, a second procedure called a blood patch may be necessary to treat it. This involves taking a sample of your blood and injecting it in your back.