Clinical Trial of NXT007 for the Prophylactic Treatment of Hemophilia A in Infants and Children

1. Why is this study needed?

Hemophilia A (HA) is a health condition where the blood doesn’t clot as it should. People with HA don’t have enough of a specific blood clotting protein, called factor 8. This makes them bleed for a longer time after they get a cut or injury. It can cause spontaneous bleeding inside joints (e.g. knees, elbows, ankles) and muscles, resulting in pain and difficulty with physical activities. It can also lead to abnormally long menstruation in females, and other pregnancy-related complications. Bleeding in affected joints can lead to arthritis, starting as young as school age. Sometimes, bleeding in the brain or other parts of the body (such as the gut) can happen requiring immediate medical attention. Preventing bleeds and keeping joints healthy are key goals in the treatment of hemophilia.

Current treatments to reduce risk of bleeds (prophylaxis) include regular infusions of factor 8 replacement into a vein that need to be given every few days. This treatment can stop working in some people who develop ‘inhibitors’ against it. A ‘non-factor’ medicine such as emicizumab can also be used, which copies the way factor 8 works and is given as injections under the skin every 1 to 4 weeks. However, whichever current treatment is used, bleeds can still sometimes happen, and extra treatment is needed if they are injured or need surgery. Better treatments are needed to help people with HA live more freely, without the risk, worry, and effects of bleeding.

This study is testing a medicine called NXT007. It is being developed to treat HA.

NXT007 is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved NXT007 for the treatment of HA. This study aims to test how safe NXT007 is and how well it helps protect against bleeding.

2. Who can take part in the study?

Children under 12 years of age, or teenagers aged 12 to 17 years with a body weight under 40 kg, can take part in the study if they have severe or moderate HA with or without inhibitors against factor 8. They can also join if they have mild HA with inhibitors against factor 8 and a reduction in their own factor 8 levels (less than 5% of what is normal) for a year or longer.

Children and teenagers may not join the study if they are allergic to any of the drugs, medical tests, or ingredients being used. They also may not be able to join if they have planned complex surgery, certain medical conditions including the risk of blood clotting (thrombosis), or if they are taking certain medicines that affect the immune system. The study doctor will check which participants can join the study.

3. How does this study work?

Children and teenagers will be screened to check if they can participate in the study. The screening period will take place up to 4 weeks before the start of treatment.

Everyone who joins this study will be given NXT007 as an injection under the skin (subcutaneous injection) every 2 weeks for the first month, and then monthly after that for at least 7 months.

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 twice in the first month, and then once a month up to the Month 8 visit. They will see how well the treatment is working and any unwanted effects participants may have. After being trained by the study doctor or nurse, caregivers or older participants can learn to give the treatment themselves. After at least 7 months of receiving treatment at the clinic, participants may have the option to manage the treatment at home every other month.

After the main treatment period, participants can choose to stay in the study for a long-term follow-up period. During this time, participants can continue to receive NXT007 once a month for at least 1 year. The study doctor will see participants during the first and the third months, and then once every 3 months after that. Participants will have 3 follow-up visits 1, 6, and 12 months after their last dose of NXT007, during which the study doctor will check on the participant’s well-being. Total time of participation in the study will be about 4 years or longer. 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 bleeding episodes participants may have in a year that need treatment. These will be counted from Month 2 to the end of the main study at Month 8, and used to estimate how many bleeds a participant might have over a full year. Other key results measured during this same time in the study include:

• The number of ‘all’ bleeds participants have (whether a treatment is given or not) The number of bleeds with no clear cause that need treatment
• The number of bleeds in the joints over time that need treatment
• The number of bleeds in a joint that has a history of frequent bleeds (target joint) that need treatment
• The number of participants with no bleeds that need treatment
• The number of injections and the amount of extra medicine used to stop bleeds over a year
• Changes in the time, effort, and daily focus caregivers spend managing the treatment
• The number and seriousness of unwanted effects
• How easy or difficult it is to give the injection
• The amount of NXT007 in the blood at specific times and how it 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 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.

NXT007: NXT007 has had limited testing in humans. Therefore, the unwanted effects of this medicine are not fully known now. Participants will be told about the possible unwanted effects of NXT007 based on laboratory studies or knowledge of similar medicines. Known unwanted effects include loss of bleed protection due to antibodies against NXT007 and also a possible increase in liver enzymes.

NXT007 will be given as an injection under the skin. Known unwanted effects of injection include a reaction on the skin where it has been pricked with a needle to give a treatment.

The study medicine may be harmful to an unborn baby. Female participants who can get pregnant must take precautions to avoid exposing an unborn baby to the study treatment.