Continuation Study on Efanesoctocog Alfa for Safety and Efficacy in Severe Haemophilia A Patients Post-Previous Trial Completion

The primary objective of this multinational, prospective, open-label, roll-over study is to collect safety and tolerability data of **efanesoctocog alfa** in previously treated patients with severe **haemophilia A**. This is clinically relevant as it aims to ensure the continued safety of the treatment in a real-world setting, providing essential data on adverse effects and overall patient tolerance. Additionally, the study seeks to gather further data on the efficacy of efanesoctocog alfa as a prophylaxis treatment and in the management of bleeding episodes. This is crucial for understanding the therapeutic benefits and optimizing treatment protocols for patients with severe haemophilia A.

The clinical trial involves participants diagnosed with **Haemophilia A**, focusing on both male and female subjects. The study population includes individuals across various age ranges, specifically children, adolescents, and adults. Participants are previously treated patients with severe **Haemophilia A** and are part of a vulnerable population. The trial aims to gather safety and tolerability data on efanesoctocog alfa, as well as its efficacy as a prophylaxis treatment and in managing bleeding episodes. The sponsor has not provided the total number of participants involved in the study. Selection criteria include the completion of specific parent studies and the ability to provide informed consent, with additional assent required for minors. Participants are expected to maintain compliance with study protocols, including the use of a study diary. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and efficacy of **efanesoctocog alfa** in patients with severe **haemophilia A** who have completed a previous trial with the investigational product. This is a multinational, prospective, open-label, roll-over study. The trial will provide post-trial access to treatment and aims to collect further data on the prophylactic efficacy and treatment of bleeding episodes. The study is expected to commence recruitment on March 20, 2024, and conclude by March 1, 2027, with a maximum treatment period of 156 weeks per participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of a parent study and ongoing clinical benefit from **efanesoctocog alfa**. The inclusion visit will ensure no interruption in prophylaxis dosing. Follow-up visits will be scheduled to monitor the occurrence of adverse events, including serious adverse events and adverse events of special interest, as well as to assess the continued efficacy of the treatment. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.

Participant involvement is expected to last up to 156 weeks, contingent upon continued clinical benefit and adherence to study protocols. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or withdrawal of consent. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the collected data, contributing valuable insights into the long-term management of **haemophilia A** with **efanesoctocog alfa**.

The clinical trial involves the administration of **BIVV001 - efanesoctocog alfa**, an experimental medication designed for patients with severe **haemophilia A**. The active substance, **efanesoctocog alfa**, is a recombinant human coagulation factor VIII Fc - von Willebrand factor - XTEN fusion protein. This medication is provided in the form of a **powder for solution for injection** or as a **powder and solvent for solution for injection**. The pharmaceutical form is intended for **intravenous injection**. The dosing regimen specifies a maximum daily dose of 50 IU/kg, with a total maximum dose of 7800 IU/kg over a treatment period of up to 156 weeks. The medication is not formulated for pediatric use and is designated as an orphan drug under the designation number EU/3/19/2176.

Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed regimen. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The primary objective of the trial is to collect safety and tolerability data, as well as efficacy data on the prophylactic use of efanesoctocog alfa and its effectiveness in treating bleeding episodes in previously treated patients with severe haemophilia A. The trial is conducted by Swedish Orphan Biovitrum AB, the organization responsible for the development of the investigational product.

The efficacy of **efanesoctocog alfa** in the clinical trial will be assessed through the collection of data on its use as a prophylaxis treatment and in the treatment of bleeding episodes in patients with severe hemophilia A. The primary efficacy endpoints include the evaluation of the drug's effectiveness in preventing bleeding episodes and its therapeutic impact during such episodes. Data collection will focus on the frequency and severity of bleeding episodes experienced by participants during the trial period.

Participants will be required to maintain a study patient diary to document bleeding episodes and any related treatment interventions. This diary will serve as a critical tool for capturing patient-reported outcomes, which will be analyzed to determine the efficacy of the treatment. The trial is designed to ensure continuous prophylaxis dosing with efanesoctocog alfa, with an emphasis on minimizing interruptions between the parent study and the current trial. The efficacy data will be collected and analyzed throughout the study duration, which is estimated to conclude by March 2027.