HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome

To be considered for this study, individuals must have a confirmed diagnosis of Angelman syndrome due to a specific gene change (called a 'UBE3A deletion' or 'UBE3A mutation'). The study is open to both males and females between birth and 50 years of age. For those under 18, a parent or legal guardian would need to agree to their participation.

It's important that any other treatments for Angelman syndrome, such as seizure medications, sleep aids, or special diets, have been stable for at least three months before joining. This helps the researchers understand the effects of the new study medicine more clearly. One unique request is that participants (or their guardians) agree not to share personal or study information on social media until the study is officially finished.

However, some people would not be able to take part. This includes those whose Angelman syndrome is caused by a different genetic change (called 'paternal uniparental disomy' or 'imprinting defect'). Also, if someone has other serious medical conditions that the doctor thinks would make taking part unsafe, or if they have poorly controlled seizures, they would not be eligible. People who have certain bone or bleeding problems, or have had gene therapy in the past, also cannot join. If you've been vaccinated against COVID-19, that's absolutely fine, you can still participate.

If you join the HALOS study, you would first go through a screening period to check if you meet all the requirements. The study medicine, ION582, is given directly into the fluid around the spinal cord (this is called an 'intrathecal' injection). This is similar to how some pain medications are given.

The study is divided into several parts. Part 1 involves receiving increasing doses of the medicine over 13 weeks, followed by at least 12 weeks of monitoring. If you complete Part 1, you might then move to Part 2, which involves receiving the medicine for 49 weeks, again followed by a monitoring period. For those who complete Part 2, there’s an option to continue receiving the medicine for up to another three years, followed by a final monitoring period. This means participating could involve regular hospital visits over several years, with check-ups, assessments, and the medicine being given. The full duration of the study for an individual could extend for several years.