A 12-week study to investigate how the body handles alogabat once it is swallowed, how safe it is, and whether it could be effective in treating the symptoms of AS

1. WHY IS THIS STUDY NEEDED?

Angelman syndrome (AS) is a rare genetic disorder that affects all areas of a child’s development, including thinking, language and movement. The disorder commonly also affects sleep and behaviour and causes frequent seizures. Currently, there is no treatment that would address the core symptoms of AS.

This study is testing a medicine called alogabat. It is being developed to treat AS. Alogabat is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved alogabat for the treatment of AS.

The main cause of AS is a problem with a gene called UBE3A, but sometimes there can be issues with other genes too, including those coding proteins that are necessary to build the GABAA α5 receptor. This receptor plays a major role in the body e.g., in brain development, learning, sleep, and seizure control, among others. Such forms of AS are known as “deletion AS”.

Alogabat is designed to help the remaining receptors to perform their function and thus could potentially make up for their reduced number. This may improve various symptoms of AS.

The first part of the study aims to test how safe alogabat is in children at different doses, and to understand what happens to alogabat once it is in the body.

The second part of the study aims to test whether alogabat can improve abnormalities in brain activity that are typical for AS.

Both parts of the study aim to assess how safe alogabat is in children with AS.

2. WHO CAN TAKE PART IN THE STUDY?

People of 5-17 years of age with Angelman syndrome with the “deletion” subtype can take part in the study if:

• they have a genetic report confirming that they have deletion AS,
• can undergo blood draws, electrocardiograms and brain wave measurements (EEG), and
• have a stable caregiver (e.g., a parent) who accompanies them during the study.

People may not be able to take part in this study if

• they have any other type of Angelman syndrome other than deletion AS

• they need to take certain drugs that could interfere with alogabat, or if

• they have certain kinds of heart disease or a recent history of cancer.

People who are pregnant, or currently breastfeeding cannot take part in the study.

3. HOW DOES THIS STUDY WORK?

Participants will be screened to check if they are able to participate in the study. The screening period will take place from 42 to 15 days before the start of treatment.

Everyone who joins this study will be given alogabat as a tablet every day for 12 weeks.

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants every 2-4 weeks. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have two follow-up visits 2 and 6 weeks after completing the study treatment, during which study doctor will check on the participant’s well-being. Total time of participation in the study will be about 24 weeks. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. WHAT ARE THE MAIN RESULTS MEASURED IN THIS STUDY?

The main results measured in the study are: 

In Part 1: to assess the level of the drug in the blood at day 1, week 2 and week 12 of treatment.

In Part 2: to assess if the medicine has worked are the change in brain activity patterns from pre-baseline to week 2, week 4, and week 12. 

Other key results measured in the study include the number of unwanted effects measured from baseline to week 12.

5. ARE THERE ANY RISKS OR BENEFITS IN TAKING PART IN THIS STUDY?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future. 

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

RISKS ASSOCIATED WITH THE STUDY DRUG

Participants may have unwanted effects of the drug used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

ALOGABAT

Participants will be told about the known unwanted effects of Alogabat, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. 

Alogabat will be given as an oral tablet (given by mouth).

The study medicine(s) may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.