Nuwiq Dosing and outcomes In the ManagEment of women/girls with haemophilia A Needing FVIII treatment for Surgery – an International, Open-label, Non-controlled study (NuDIMENSION)

The primary objective of this study is to evaluate the overall perioperative **haemostatic** efficacy of Nuwiq in women and girls with **haemophilia A** undergoing major surgery. This is clinically relevant as it addresses the critical need for effective management of bleeding in this patient population during surgical procedures, where maintaining adequate haemostasis is essential to prevent excessive blood loss and associated complications.

Secondary objectives include: - Assessing the intra- and post-operative surgical haemostatic efficacy of Nuwiq. - Evaluating perioperative coagulation factor FVIII plasma levels. - Determining the perioperative efficacy of Nuwiq as per the criteria recommended by the World Federation of Hemophilia (WFH). - Assessing the perioperative safety of Nuwiq. - Evaluating the perioperative use of allogeneic blood products, including red blood cells, platelets, and other blood products.

The clinical trial involves a total of **5 participants** diagnosed with **Haemophilia A**, specifically targeting a female-only population. The study includes women and girls aged 12 years and older, who are scheduled to undergo major elective surgery necessitating Factor VIII (FVIII) treatment. Participants were selected based on their medical history indicating FVIII activity levels between 1% and less than 40%. The trial population is characterized by a vulnerable group, as it includes individuals with a significant medical condition requiring specialized care. The selection criteria ensure that all participants have provided freely given written informed consent. The study does not include male subjects, and no specific lifestyle considerations such as diet or physical activity are highlighted in the available data.

The clinical trial is designed to evaluate the **haemostatic efficacy** of Nuwiq in women and girls with **Haemophilia A** undergoing major surgery. This is an open-label, non-controlled study, classified as a phase IV trial, which investigates the use of Nuwiq, a coagulation factor VIII product, in a real-world setting. The trial is expected to run from June 2023 to March 2025, with a maximum treatment period of 30 days for each participant. The study involves the administration of Nuwiq via **intravenous injection** in accordance with its approved use for preventing bleeding during surgery.

Participants will be women or girls aged 12 years or older with **Haemophilia A**, having a factor VIII activity between 1% and 40%, and scheduled for major elective surgery. The trial will begin with a screening visit to confirm eligibility based on medical history and informed consent. The primary endpoint is the overall haemostatic efficacy of Nuwiq, assessed at the end of surgery and the postoperative period by the surgeon and investigator, respectively. Secondary endpoints include intraoperative and postoperative haemostatic efficacy, perioperative FVIII plasma levels, and the incidence of adverse events, thrombotic events, and FVIII inhibitor formation.

Study visits will include the initial screening, followed by perioperative assessments immediately before and after Nuwiq administration, and a final end-of-study visit to evaluate wound healing and overall outcomes. Participants are expected to be involved for the duration of their surgical and recovery period, up to a maximum of 30 days. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is considered low-intervention, as it aligns with the existing marketing authorization of Nuwiq and poses minimal additional risk compared to standard clinical practice.

The clinical trial involves the administration of **Nuwiq**, a recombinant human coagulation factor VIII, known as **simoctocog alfa**. This experimental medication is provided in various dosages, including 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 2500 IU, 3000 IU, and 4000 IU. Each formulation is presented as a **powder and solvent for solution for injection**, intended for intravenous administration. The pharmaceutical form is a solution for injection, and the treatment is administered via intravenous injection. The maximum treatment period for each dosage is 30 days. The dosing schedule is determined based on the individual needs of the participants, with the aim of maintaining adequate factor VIII levels during the perioperative period. Participant compliance is monitored through regular assessments of factor VIII activity levels and clinical evaluations.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The focus is solely on evaluating the efficacy and safety of Nuwiq in managing women and girls with **hemophilia A** undergoing major surgery. The trial is designed to assess the overall perioperative hemostatic efficacy of Nuwiq, with no additional medications or interventions being tested concurrently. The study protocol ensures that all participants receive the same investigational product, with dosing tailored to their specific clinical requirements.

The efficacy of Nuwiq in the management of women and girls with **hemophilia A** undergoing major surgery will be assessed through a series of predefined endpoints. The primary endpoint involves evaluating the overall perioperative haemostatic efficacy of Nuwiq. This assessment will be conducted at the end of surgery by the surgeon and at the end of the postoperative period (POP) by the investigator. The overall haemostatic efficacy will be adjudicated by the Independent Data Monitoring Committee (IDMC) using a pre-defined algorithm. The end of the POP for a surgical event is defined as the completion of wound healing, as determined by the investigator.

Secondary endpoints include the assessment of intraoperative and postoperative haemostatic efficacy using a 4-point ordinal scale. Additionally, perioperative FVIII plasma levels will be measured immediately before (≤30 minutes) and after (15-30 minutes) Nuwiq injections. The perioperative haemostatic efficacy will also be assessed using the 4-point scale recommended by the World Federation of Hemophilia (WFH). Other secondary endpoints include the incidence of adverse events (AEs), thrombotic events, and FVIII inhibitor formation, as well as the number of allogeneic blood products transfused.