Phase 2 Study on the Efficacy and Safety of Riliprubart in Antibody-Mediated Rejection Prevention and Treatment in Adult Kidney Transplant Recipients

The primary objective of this study is to evaluate the efficacy of **BIVV020** in the prevention and treatment of antibody-mediated rejection (AMR) in adult kidney transplant recipients. This is clinically relevant as AMR is a significant cause of transplant rejection, and effective management can improve transplant outcomes and patient survival. The study is divided into two cohorts: Cohort A focuses on the prevention of AMR, while Cohort B addresses the treatment of active AMR.

Secondary objectives include:

• Assessing the overall efficacy of BIVV020 in the prevention or treatment of AMR.
• Characterizing the safety and tolerability of BIVV020 in kidney transplant participants.
• Characterizing the pharmacokinetic profile of BIVV020 in kidney transplant participants.
• Evaluating the immunogenicity of BIVV020.

The clinical trial involves a total of **15 participants** who are being studied for the prevention and treatment of **transplant rejection**. The study population includes both male and female subjects, with an age range that spans from 18 to 65 years. Participants were selected based on their health status, specifically those with chronic kidney disease who are either awaiting a kidney transplant or have already received one and are diagnosed with active antibody-mediated rejection (AMR). The trial includes individuals with a body mass index (BMI) of 40 kg/m² or less. Participants are required to adhere to specific contraceptive measures during the treatment period and for at least 49 weeks following the last administration of the investigational medicinal product. The trial population is considered vulnerable, and the selection process was guided by the investigator's judgment and local practice standards. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **randomized**, Phase 2, open-label study to evaluate the preliminary efficacy, safety, and pharmacokinetics of BIVV020 in the prevention and treatment of antibody-mediated rejection (AMR) in adult kidney transplant recipients. The trial is structured into two cohorts: Cohort A focuses on the prevention of AMR in participants with chronic kidney disease receiving a kidney transplant, while Cohort B targets the treatment of active AMR in kidney transplant recipients. The study will utilize a **controlled** approach, with participants receiving either the investigational medicinal product (IMP) BIVV020 in combination with standard of care (SOC) or SOC alone.

The trial is expected to span approximately four years, with an estimated end date of December 3, 2026. Participant involvement will commence with an inclusion (screening) visit to assess eligibility based on criteria such as a body mass index (BMI) of ≤ 40 kg/m² and the requirement for contraceptive use during and after the treatment period. Following the screening, eligible participants will undergo a series of study visits, including baseline assessments, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to evaluate the primary and secondary endpoints.

The primary endpoints include the treatment failure rate for Cohort A and the AMR resolution rate for Cohort B. Secondary endpoints encompass changes in renal function, allograft histopathology, graft survival, adverse events, and pharmacokinetic parameters of BIVV020. Participants are expected to remain in the study for the full duration unless they meet conditions for early termination, such as withdrawal of consent, significant protocol deviations, or adverse events that necessitate discontinuation. The investigational product, **riliprubart**, will be administered as a **solution for injection** via the subcutaneous route, with a maximum daily dose of 50 mg/kg and a maximum treatment period of 49 days.

The clinical trial involves the administration of **riliprubart**, an experimental medication formulated as a **solution for injection**. The active substance, **riliprubart**, is a protein of non-specific origin, developed by Sanofi Aventis Recherche et Développement (SAR). The pharmaceutical form is a solution intended for subcutaneous administration. The dosing regimen specifies a maximum daily dose of 50 mg/kg, with the same maximum total dose amount, administered over a treatment period not exceeding 49 days. The medication is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed to assess the efficacy, safety, and pharmacokinetics of the investigational product without the inclusion of additional therapeutic agents. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial does not involve any devices or additional substances beyond the investigational product.

The efficacy of the investigational product BIVV020 in the clinical trial will be assessed through a series of primary and secondary endpoints. For Cohort A, the primary endpoint is the treatment failure rate, while for Cohort B, the primary endpoint is the **antibody-mediated rejection (AMR)** resolution rate. Secondary endpoints include changes in renal function from baseline, assessed by central laboratory measurements of estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation and the protein: creatinine ratio. Additionally, changes in allograft histopathology Banff score, graft survival as predicted by iBOX, and the assessment of adverse events (AEs) will be evaluated. The trial will also measure changes in the systemic lupus erythematosus (SLE) panel and plasma exposure of BIVV020, assessing pharmacokinetic parameters such as Cmin and AUC. The presence of anti-BIVV020 antibodies in participants will also be monitored.