Evaluation of Long-Term Efficacy of Efanesoctocog Alfa Prophylaxis on Joint Health in Patients with Hemophilia A: A Low-Interventional Study

The primary objective of this study is to describe the long-term **effectiveness** of efanesoctocog alfa prophylaxis in preventing joint bleeds in patients with **Haemophilia A**. This is clinically relevant as it aims to improve joint health and reduce bleeding episodes, which are critical concerns in the management of Haemophilia A.

Secondary objectives include:

• Describing the effectiveness of efanesoctocog alfa prophylaxis on other outcomes such as annualized bleeding rate, number of injections used to control a bleeding event, change in HJHS score, and target joint development.
• Describing the real-world usage of efanesoctocog alfa treatment.
• Assessing the relative effectiveness and real-world usage of efanesoctocog alfa treatment compared to prior haemophilia treatment.
• Describing the effectiveness and usage of efanesoctocog alfa for perioperative management.
• Evaluating joint health structural outcomes under efanesoctocog alfa prophylaxis via ultrasound using Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US).
• Describing treatment preference and health-related outcomes in terms of quality of life, pain, and physical activity in patients during real-world prophylactic treatment with efanesoctocog alfa.
• Describing the long-term safety of efanesoctocog alfa prophylaxis in a real-world setting.

The clinical trial involves a total of **60 participants** diagnosed with **Haemophilia A**, aiming to evaluate the long-term effectiveness of efanesoctocog alfa prophylaxis in preventing joint bleeds. The study population includes both male and female subjects, with an age range encompassing children, adolescents, and adults. Participants were selected based on their prior prescription of efanesoctocog alfa prophylactic treatment within six months before enrollment or at the latest during the enrollment visit, in accordance with local regulations. All participants have a documented history of prophylactic treatment with any haemophilia product for at least 12 months prior to the study. The trial includes individuals who are capable of providing informed consent and are willing to adhere to the study's visit schedule and assessments. The population is considered vulnerable, and participants are required to document all bleeding episodes and treatments. Additionally, a subgroup of participants will undergo annual ultrasound assessments on specific joints. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the long-term effectiveness of **efanesoctocog alfa** prophylaxis in preventing joint bleeds in patients with **haemophilia A**. This study is categorized as a low-intervention trial and will follow a prospective observational design. The trial will be conducted over an estimated duration from May 2025 to December 2028, with the primary objective of assessing the annualized joint bleeding rate (AjBR) over the prospective period. Secondary endpoints include the annual bleeding rate, the number of injections and total dose required to control a bleeding event, changes in the Hemophilia Joint Health Score (HJHS) from enrolment to months 12, 24, and 36, and the development, resolution, and recurrence of target joints.

Participants will be required to attend several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of haemophilia A and prior prophylactic treatment history. Follow-up visits will be scheduled to monitor the effectiveness of the treatment and to collect data on bleeding episodes and joint health. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 156 weeks. Conditions that may lead to early termination from the study include non-compliance with the study protocol or withdrawal of consent.

Throughout the trial, participants will receive **efanesoctocog alfa** via intravenous injection, with the dosage tailored to individual needs. The study will ensure that all participants are capable of providing informed consent and are willing to adhere to the visit schedule and study assessments, including mandatory evaluations such as the HJHS and patient-reported outcomes (PROs). Additionally, a subgroup of participants will undergo annual ultrasound assessments of the index joints. The trial aims to provide valuable insights into the real-world application of **efanesoctocog alfa** in managing joint health in individuals with **haemophilia A**.

The clinical trial involves the administration of **efanesoctocog alfa**, a recombinant human coagulation factor VIII Fc - von Willebrand factor - XTEN fusion protein, also known by its synonyms rFVIIIFc-VWF-XTEN, BIVV001, and BIVV-001. This experimental medication is provided in various dosages, including ALTUVOCT 250 IU, 500 IU, 1,000 IU, 2,000 IU, 3,000 IU, and 4,000 IU, all formulated as a **powder and solvent for solution for injection**. The pharmaceutical form is a solution for injection, and the route of administration is **intravenous injection**. The dosing unit is expressed in international units per kilogram (IU/kg), although specific dosing schedules and maximum daily doses are not detailed in the provided data. The maximum treatment period for the trial is 156 weeks.

There are no non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, mentioned in the trial data. The trial's primary objective is to evaluate the long-term effectiveness of efanesoctocog alfa prophylaxis in preventing joint bleeds in patients with **Haemophilia A**. Participant compliance monitoring and specific dosing schedules are not explicitly detailed in the provided information. The trial is conducted under the authorization of the European Union, with the marketing authorization number EU/1/24/1824, and the product is manufactured by Swedish Orphan Biovitrum AB (Publ).

Efficacy in this clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the **Annualised Joint Bleeding Rate (AjBR)** over the prospective period. Secondary endpoints include the Annual Bleeding Rate over the prospective observation period, the number of injections and total dose required to control a bleeding event, changes in the Haemophilia Joint Health Score (HJHS) from enrolment to Months 12, 24, and 36, and the development, resolution, and recurrence of target joints on both a patient and joint level during the period on efanesoctocog alfa.

Data collection will involve mandatory study assessments, including the HJHS and patient-reported outcomes (PROs). Participants will be required to document all bleeding episodes and any treatments for those episodes. For the HEAD-US subgroup, annual ultrasound assessments on the index joints (ankles, elbows, knees) will be conducted. The trial is designed to evaluate the long-term effectiveness of efanesoctocog alfa prophylaxis in preventing joint bleeds in patients with **Haemophilia A**. The study is categorized as a low-intervention trial, with an estimated end date of December 2, 2028.