A study to look at how safe emicizumab treatment is and how well it works to prevent bleeds in children with haemophilia A (without factor 8 inhibitors) who started emicizumab in their first year of life

1. Why is this study needed?

Haemophilia A is a health condition where the blood doesn't clot as it should. People with haemophilia A don't have enough of a select protein, called ‘factor 8’ (sometimes written as ‘FVIII’). This makes them bleed for a longer time after they get a cut or injury. People with haemophilia can also bleed for no clear cause (spontaneous bleeding) in their joints (such as knees, elbows, ankles), muscles and other soft tissues (such as skin or fat), and have difficulties with physical activities. Preventing joint bleeds and maintaining good joint health are key goals when treating haemophilia.

Treatments for haemophilia A focus on providing the missing factor 8 protein, to help blood clot after a cut or injury and prevent or reduce the bleeds associated with the disorder. On-demand and regular factor 8 replacement therapy are used to treat and prevent bleeds. However, it needs to be given directly into a vein. Also, the body’s natural defence (immune system) can develop antibodies that stop the therapy working (these are known as ‘factor 8 inhibitors’).

This study is testing a medicine called emicizumab. It can be given as an injection under the skin and less often (weekly, every other week or every four weeks) than factor 8 replacement therapy. Emicizumab is approved by health authorities (like the U.S. Food and Drug Administration and the European Medicines Agency) for treating haemophilia A in people with or without factor 8 inhibitors, and in all ages. It is used to prevent or reduce the number of bleeding episodes. However, there is limited information available on the use of emicizumab in children when the treatment has started in the first year of life.

This study aims to test how safe and well emicizumab works and to understand how the treatment gets to different parts of the body, and how the body changes and gets rid of it in children without factor 8 inhibitors who have started emicizumab in the first year of life.

2. Who can take part in the study?

Children under 1 year of age with haemophilia A without factor 8 inhibitors can take part in the study.

Children may not be able to take part in this study if they have previously been given certain medicines within a certain time frame before the study, including emicizumab, or if they have certain other medical conditions, such as another bleeding disorder or an autoimmune disease.

3. How does this study work?

Children will be screened to check if they are able to participate in the study. The screening period will take place from 2 weeks before the start of treatment.

Everyone who joins this study will be given emicizumab, as an injection under the skin weekly for the first month. Then every 2 weeks for a year. After 1 year of treatment, participants continued to be given emicizumab every 1, 2 or 4 weeks and will be monitored for another 7 years as part of this study.

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 the first year of this study, the study doctor will see participants every week for the first 5 weeks, then every 2 or 4 weeks. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have follow-up visits every 3 months during the next 7 years. Total time of participation in the study will be about 8 years. 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 to assess if the medicine has worked are:

• The number of bleeds children have that require a treatment
• The number of all bleeds children have (whether a treatment is given or not)
• The number of bleeds requiring a treatment that do not have a clear cause
• The number of joint bleeds that require a treatment

Other key results measured in the study include:

• Joint health measured using the Hemophilia Joint Health Score (HJHS) and magnetic resonance imaging (MRI) scans during the 7-year follow-up period
• The number and seriousness of any unwanted effects
• How emicizumab gets to different parts of the body, and how the body changes and gets rid of it
• How emicizumab affects the immune system

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. The parents or carers of children 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 emicizumab
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.

Participants’ carers will be told about the known unwanted effects of emicizumab and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include pain or discomfort in the head, joint pain and a reaction on the skin where it has been pricked with a needle to give a treatment.

Emicizumab will be given as an injection under the skin. Known unwanted effects include redness, swelling or rash on the skin where it has been pricked with a needle to give a treatment.