A study to look at how well emicizumab works when given every 1, 2, or 4 weeks to prevent bleeds in people with mild or moderate haemophilia A without factor 8 inhibitors

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. People with severe haemophilia A have less factor 8 protein than people with mild or moderate haemophilia A. 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 is used to prevent or reduce the number of bleeding episodes. 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 factor 8 inhibitors, or severe or moderate haemophilia A in people without factor 8 inhibitors. When this study started, emicizumab was not approved in many countries for treating mild or moderate haemophilia A in people without factor 8 inhibitors, so it is an experimental medicine in this study.

This study aims to see how well emicizumab works when given every 1, 2, or 4 weeks to prevent bleeds in people with mild or moderate haemophilia A.

2. Who can take part in the study?

People who weigh at least 3kg with mild or moderate haemophilia A without factor 8 inhibitors can take part in the study.

People may not be able to take part in this study if they have another bleeding disorder, or another medical condition that increases the risk of bleeding. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place from 1 month 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, participants or their caregivers can choose with the study doctor whether to have:

• A low dose (1.5mg for every kg of body weight) of emicizumab once every week, OR
• A medium dose (3mg for every kg of body weight) of emicizumab once every 2 weeks, OR
• A high dose (6mg for every kg of body weight) of emicizumab once every 4 weeks

Injections can be given in the home by participants or their caregivers after training is given, or by a nurse. After 1 year of treatment, participants are invited to continue emicizumab treatment for 2 more years in the study extension. 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 weekly for the first month, then once a month for the first year of treatment. They will see how well the treatment is working and any unwanted effects participants may have. In the study extension, participants will be seen every 6 months. Participants who decide to stop treatment will have a follow-up visit 6 months after their last dose of study treatment, during which the study doctor will check on the participant’s wellbeing. Total time of participation in the study could be up to 4 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 result measured in the study to assess if the medicine has worked is the number of bleeds per year participants have that require a treatment.

Other key results measured in the study include:

• The number of all bleeds participants have (whether a treatment is given or not)
• The number of joint bleeds over time
• The number of bleeds over time with no clear cause
• Joint health during the study, measured using the Hemophilia Joint Health Score (HJHS)
• How a person's health and haemophilia A symptoms impact their daily life and their ability to function and enjoy life. This includes how active participants are, and how women and girls who are able to become pregnant feel during their period
• Whether participants prefer their previous factor 8 treatment or emicizumab
• 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. 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 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 or their caregivers 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 treatment was given.

The study medicine may be harmful to an unborn baby. Women and girls who can become pregnant must take precautions to avoid exposing an unborn baby to the study treatment.