Prospective Evaluation of Subcutaneous Administration of Daratumumab by the FreedomEDGE® Infusion System

This clinical investigation is designed to generate clinical evidence supporting evaluation of the performance and safety of the FreedomEDGE® Infusion System for subcutaneous (SC) administration of daratumumab. Daratumumab is a human IgG1κ monoclonal antibody directed against CD38 and approved for the treatment of multiple myeloma. The availability of a subcutaneous formulation has substantially reduced administration time compared with intravenous infusion while maintaining therapeutic effectiveness and improving treatment convenience. The approved SC formulation is administered continuously over approximately 3-5 minutes. In routine clinical practice, SC administration of daratumumab requires nurses to manually apply continuous pressure to the syringe plunger throughout the injection period in order to maintain administration conditions consistent with the approved product labelling. This manual procedure may introduce variability in injection duration and administration consistency and may contribute to patient discomfort, local injection-site reactions, and repetitive physical strain for healthcare professionals. The FreedomEDGE® Infusion System is a mechanical, non-electrical infusion device intended for controlled subcutaneous administration of medicinal products. The system combines a reusable infusion pump with sterile precision flow tubing and sterile High-Flo™ SubQ needle sets. Drug delivery is achieved through a constant-force spring mechanism associated with dedicated flow restriction tubing selected according to product viscosity and administration conditions. Although the device currently bears CE marking for selected approved subcutaneous therapies, administration of daratumumab is not currently included within its intended purpose. This clinical investigation is conducted within the framework of Regulation (EU) 2017/745 on medical devices (MDR) as a clinical investigation intended to establish conformity of a CE-marked device used outside its currently approved intended purpose, with the objective of supporting extension of CE marking. According to applicable European and national regulatory classification criteria, this investigation corresponds to regulatory category 1. This is a prospective, single-centre, non-randomized clinical investigation conducted in the Clinical Hematology Department of Lyon-Sud hospital (Pierre-Bénite, France). The primary objective is to evaluate the performance of the FreedomEDGE® Infusion System for subcutaneous administration of daratumumab. Device performance is defined as the ability to provide reliable, controlled, and complete administration of the prescribed dose under normal conditions of use and according to the device instructions for use. Eligible participants must be adults, diagnosed of multiple myeloma or light-chain amyloidosis; treated with monthly subcutaneous daratumumab. Participants are recruited among patients routinely followed in the Clinical Hematology Department and receiving daratumumab in the day hospital setting. Enrolment occurs once treatment reaches the monthly administration phase, corresponding to patients who have already received several prior manual SC injections and therefore have prior experience with standard administration. Approximately 100 evaluable administrations are planned. Based on expected routine activity and patient flow, recruitment is expected to be completed over approximately six months. At Screening and Inclusion time (T0), potential participants are identified during routine follow-up within the hematology department. Patients whose daratumumab schedule reaches monthly administration are informed about the study by a physician co-investigator. Patients receive oral and written information describing study objectives, procedures, constraints, potential risks, safety measures, and participant rights, including the right to refuse participation or withdraw consent at any time without impact on standard care. Written informed consent is obtained before any study-specific procedure. Eligibility criteria are subsequently verified in full before formal enrolment. Clinical evaluation at inclusion is limited to routine assessment and observation of the future injection site. The study intervention is performed at the participant's next scheduled monthly administration visit (M1). Subcutaneous daratumumab is administered using the FreedomEDGE® Infusion System according to the device instructions for use and following nurse training. Administration is performed using a prefilled daratumumab syringe connected to dedicated precision flow tubing (reference F1200) and a sterile High-Flo™ SubQ needle set (24G, 9 mm). After skin preparation and placement of the needle, the syringe is loaded into the device and administration is initiated. Following administration, the following data are collected: device traceability information; administration duration; total injected volume compared with prescribed volume; occurrence and description of any device malfunction; corrective actions implemented to complete administration if required; occurrence of local skin reactions; occurrence of systemic adverse events. Following administration, nurses complete a study-specific questionnaire assessing: pain associated with administration; ease of use; ease of injection; device reliability; overall satisfaction; preference between manual administration and device-assisted administration; interest in extending use of the system to other therapies. Patients complete a study-specific questionnaire assessing: injection experience; comfort; satisfaction; preference between manual administration and device-assisted administration. Questionnaires are completed shortly after administration and require approximately five minutes. The end-of-study visit corresponds to the M1 administration visit. Participant follow-up ends after completion of this visit. No biological samples are collected specifically for study purposes. No additional visits, laboratory tests, imaging procedures, or invasive assessments are required beyond standard care. Expected benefits for patients include more standardized and controlled administration, improved injection comfort, and reduction of injection-related discomfort. Expected benefits for healthcare professionals include reduced physical strain associated with repeated manual injections and improved working conditions. Risks associated with device use are expected to remain comparable to routine subcutaneous administration and include administration error, contamination, injection-site trauma, and local reactions such as redness, swelling, or pain. Appropriate monitoring and risk mitigation procedures are implemented throughout the study. In case of device malfunction, administration may be completed manually according to standard practice. Overall, considering the anticipated improvements in administration standardization and user experience together with the limited and controlled risks associated with the procedure, the expected benefit-risk profile is considered favourable.