In order to participate in this study, you must be able to speak and read Dutch fluently.

The target population for this trial, a phase I randomized double-blind controlled trial, are men and women aged 50-74 years diagnosed with mild-stage Alzheimer’s disease.

The research agent ISIS 814907 is a new drug that is being developed against Alzheimer’s disease. With this study, the researchers want to learn more about the safety and working mechanisms of the drug. The study drug is administered via a lumbar puncture (spinal tap).

The research is carried out in the Brain Research Center in collaboration with the Amsterdam UMC location VUmc.

The research is divided into three stages.

This study is commissioned by Ionis.

This text has been directly translated from the Dutch trial description as approved by the Ethical Committee.

During four visits over a period of up to eight weeks, it will be determined whether you meet the study criteria and whether your general health allows participation in the study. If so, you can participate in the study. The selection includes blood tests, physical examinations, memory tests, questionnaires, an MRI scan, a spinal tap, and a PET scan.

In this study, the study drug is compared with placebo. The chance that you will receive the study drug compared to placebo is 3: 1. Participants are divided into four different groups (cohorts). The first two cohorts (A and B) have already been completed.

• Cohort C: 12 research participants. In this cohort, you will receive 4 injections at a dose of 60 mg over 24 weeks. (Day 1, 29, 57, 85).
• Cohort D: 16 research participants. In this cohort, you will receive 4 injections at a dose of 70 mg over 24 weeks. (Day 1, 29, 57, 85).

Depending on interim results, the dosages may still be adjusted. The study drug will be administered in the hospital, where you will then stay for several hours or overnight for observation. Blood tests and checks of vital signs and physical and neurological examinations will be performed. Two days after each injection, you will be called by someone from the research team who will be informed about your health situation and any side effects. One week after the injection, you will visit the research center. During these visits, checks are done (inquiries about side effects and medication use) and physical and neurological examination will take place.

At 3, 7, and 11 weeks after completing the study drug intake period, visits will take place for blood tests, physical examinations, cardiac tracing, and neuropsychological tests. A spinal tap will also be performed at week 3 and week 7 after the last injection. The visit 11 weeks after the last injection also includes an MRI and PET scan. Another 12 weeks after that, a final visit will take place with questionnaires and memory tests, blood tests, physical examination, heart film, and a spinal tap, among other things.

A total of approximately 14 visits will take place during a period of 37 weeks to the research center (the MRI department or PET department) and 4 overnight stays in the hospital where you will be administered the research substance.

• You have been diagnosed with mild-stage Alzheimer’s disease
• You are a man or woman aged 50 to 74
• The use of Alzheimer’s medication is permitted if it has been stable for at least 8 weeks.
• You have someone close to you/a caregiver who can accompany you during a few visits to the research center and answer questions about your health and functioning, among other things.