Hemophilia A, Prophylaxis of bleeding

Trial Purpose

Researchers are looking for a better way to treat people who have hemophilia A.
Hemophilia A is a genetic bleeding disorder that is caused by the lack of a protein in the blood called “clotting factor 8” (FVIII). FVIII is naturally found in the blood where it causes the blood to clump together to help prevent and stop bleeding. People with lower levels of FVIII or with FVIII that does not work properly may bleed for a long time from minor wounds, have painful bleeding into joints, or have internal bleeding.

The study treatment, Jivi (also called damoctocog alfa pegol), is already available for doctors to prescribe to people with hemophilia A to treat and prevent bleeding. It works by replacing the missing FVIII, or the FVIII that does not work properly.

People with hemophilia A need frequent injections of FVIII products into the vein. So called standard half-life (SHL) products need to be given 2 to 4 times a week for the prevention of bleeding. In recent years, new products like Jivi called extended half-life (EHL) products have become available. These products last longer in the body so that they require to be given less often with injections every 3-5 days. Thus, these treatments may be easier and more comfortable to stick to in daily life. There is no general plan concerning the best amount of treatment and the frequency of injections for the prevention of bleeding, since the severity may be different and individual risk factors have to be considered. Doctors often decide on a treatment plan based on their experience.

The main purpose of this study is to learn how well a new scoring approach works to select a treatment plan for the prevention of bleeding in people with hemophilia A who switch their treatment from SHL products to Jivi. Different types of information are used to calculate the risk score like bleeding history, certain biological factors, or physical activity of the participant.
All participants will receive Jivi for 6 months.
In the first four weeks, all participants will receive Jivi 2 times a week at a dose level of 40 IU per one kilogram body weight (also known as 40 IU/kg/dose). Then, based on their risk score, each participant will be assigned to one of three treatment plans:
•    participants with a high risk remain on Jivi administration 2 times a week at 40 IU/kg/dose
•    participants with a medium risk will switch to Jivi administration every 5 days at 50 IU/kg/dose
•    participants with a low risk will switch to Jivi administration every 5 days at 50 IU/kg/dose and after 4 weeks to a less frequent administration (e.g., every 7 days) at 60 IU/kg/dose
To check how well the new scoring approach works for choosing the right treatment plan, researchers will look at how many participants have a favourable outcome.
This means that the participant has either fewer bleeding events and takes Jivi less often or as often as the previous SHL treatment, or that the participant has a comparable number of bleeding events but needs to take Jivi less often than the previous treatment.

Each participant will be in the study for approximately 7.5 months. During this time, 4 visits to the study site and 3 phone calls are planned.
During the study, the doctors and their study team will:
•    do physical examinations
•    take blood samples
•    ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
In addition, participants are asked to write down the dates of Jivi treatments and bleeding events in an electronic diary and to fill in different questionnaires on their quality of life, health status, work/ school productivity, pain, and treatment satisfaction.

-  Participants must be ≥ 12 years of age inclusive, at the time of signing the informed
consent/assent.
 -  Previously treated patients (≥ 150 EDs) with congenital hemophilia A.
 -  Prophylaxis with any SHL FVIII product with a stable dose/regimen for at least 12 months (including at the time of screening) before entering the study and documented in medical records.
 -  Documented bleeding rate (ABR) for at least the 6 months prior to study entry.
 -  No current evidence (≥ 0.6 BU/mL) of FVIII inhibitors.
   - If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL) but has been tolerized for at least 3 years since the last positive titer with at least 3 subsequent negative inhibitor assay tests during that period, they can be enrolled.
   - If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL) but did not require tolerization and has had at least 3 subsequent negative inhibitor assay tests during a minimum period of at least 3 years since the last positive titer, they can be enrolled.
 -  If they are human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4) + lymphocyte count should be > 200/mm^3 within 1 year before entering the study and documented in medical records.
 -  Participants who are willing to complete an electronic diary (eDiary).
 -  Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
-  For adolescent participants (≥ 12 to < 18 years), a legal guardian must be available to
help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day according to the SoA (e.g. able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the PROs during the scheduled study visits; accurately and reliably dispense study intervention as directed.
 -  For adolescent participants, a legal guardian must be able to accurately maintain the child’s take-home record, including items of general health.

-  Any other inherited or acquired bleeding disorder in addition to hemophilia A. Note: von Willebrand disease should be diagnosed per local clinical practice. Participants with a diagnosis of von Willebrand disease in medical records or diagnosed at the time of screening will be excluded.
 -  Platelet count < 100,000/mm^3
 - Evidence of inhibitor to FVIII (≥ 0.6 BU/mL) within the last 3 years
 -  The participant is currently participating in another investigational drug study or has participated in a clinical study involving an investigational drug or device within 30 days of signing informed consent.
 -  The participant has a planned major surgery.
 -  Documentation of missing risk score parameters
. -  Known hypersensitivity to the drug substance, excipients, or mouse or hamster protein.
 -   Any other significant medical condition that the investigator feels would be a risk to the participant or would impede the study.
 -  Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
 -  Otherwise vulnerable participants (e.g. participants who are in custody by order of an authority).
 -  Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures (i.e. eDiary completion), restrictions, and requirements.