Evaluation of Rituximab for Relapse Prevention in Adult Minimal Change Nephrotic Syndrome: A Randomized Controlled Trial

The primary objective of this study is to demonstrate the efficacy of **Rituximab** in preventing relapse in adult patients with Minimal Change Nephrotic Syndrome (MCNS) following the initial episode and complete remission. This is achieved through two injections of Rituximab, each separated by one week, with a dosage of 375 mg/m², and the definitive withdrawal of steroids after nine weeks of treatment. The clinical relevance of this objective lies in its potential to reduce the risk of relapse after 12 months of follow-up, thereby improving long-term patient outcomes and reducing the burden of disease management.

Secondary objectives include: - Evaluating the relapse rate, defined as the number of relapses per person-year, at 18 months post-randomization. - Assessing the type, frequency, and severity of adverse events and serious adverse events within 18 months of follow-up. - Measuring the treatment burden at Week-4 before randomization, and at one week and 16 weeks post-randomization. - Identifying demographics, clinical, and/or biological risk factors for relapse at 12 and 18 months of follow-up.

The clinical trial focuses on adult participants diagnosed with **Minimal Change Nephrotic Syndrome** (MCNS). The study population includes both male and female subjects aged 18 years and older. Participants are required to have experienced their first episode of MCNS, characterized by specific laboratory findings such as an albumin level of less than 30 g/L and a urine protein/creatinine ratio of 300 mg/mmol or higher, or a biopsy-proven diagnosis. The trial does not involve a vulnerable population. Participants must be affiliated with the French healthcare system and have provided informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified as part of the study criteria.

The clinical trial is designed to evaluate the efficacy of **rituximab** in preventing relapse in adult patients experiencing their first episode of Minimal Change Nephrotic Syndrome (MCNS). This study is a randomized, double-blind, controlled trial with a primary objective to assess the incidence of MCNS relapse over a 12-month follow-up period. The trial is expected to run from July 29, 2020, to July 29, 2028, with participant involvement lasting approximately 18 months, including follow-up assessments.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), albumin levels, and renal biopsy results. Following randomization, participants will receive two intravenous infusions of rituximab, spaced one week apart, with a subsequent withdrawal of steroids after nine weeks. The primary endpoint is the incidence of MCNS relapse, defined by specific laboratory criteria, within 12 months post-randomization. Secondary endpoints include the relapse rate at 18 months, the frequency and severity of adverse events, and the assessment of treatment burden.

Study visits will include regular follow-up assessments to monitor the participants' health status, treatment adherence, and any adverse events. The end-of-study visit will occur at the conclusion of the 18-month follow-up period. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial aims to provide valuable insights into the long-term management of MCNS and the potential role of rituximab in reducing relapse risk.

The clinical trial involves the administration of **Rituximab**, marketed under the name MabThera, which is provided in two formulations: a 100 mg and a 500 mg concentrate for solution for infusion. Rituximab is a biological agent classified under the ATC code L01FA01. It is administered via **intravenous use**. The dosing regimen consists of two injections, each at a dose of 375 mg/m², separated by one week. The maximum daily and total dose is 750 mg, with a treatment period of one week. Rituximab is utilized as the test product in this study.

**Prednisolone** is used as a comparator treatment in the trial. It is administered orally in a pharmaceutical form denoted as PHF00059MIG. The active substance, **betamethasone sodium phosphate**, is a chemical compound. The maximum daily dose is 80 mg, with a total dose not exceeding 1904 mg over a treatment period of 24 weeks. Prednisolone is employed to facilitate the withdrawal of steroids after 9 weeks of treatment.

Another comparator treatment in the study is **Prednisone**, which is also administered orally. The pharmaceutical form is identified as PHF00245MIG, and the active substance is **prednisolone**, a chemical compound. The dosing schedule mirrors that of Prednisolone, with a maximum daily dose of 80 mg and a total dose of 1904 mg over 24 weeks. Prednisone serves as a standard-of-care therapy in the trial.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial aims to evaluate the efficacy of Rituximab in preventing relapse in adult patients with Minimal Change Nephrotic Syndrome following complete remission.

The efficacy of Rituximab in preventing relapse in adult patients with Minimal Change Nephrotic Syndrome (MCNS) will be assessed through a clinical trial. The primary endpoint for evaluating efficacy is the incidence of MCNS relapse during the 12 months following randomization. This is defined by the recurrence of nephrotic syndrome, indicated by a urine protein/creatinine ratio (UPCR) of ≥ 300 mg/mmol and a decreased albumin level of < 30 g/L in patients who were previously in complete remission.

Secondary endpoints include the relapse rate at 18 months of follow-up, the type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs), and the treatment burden assessed with the Treatment Burden Questionnaire. Additionally, potential risk factors for relapse will be evaluated by recording explanatory variables such as demographics, clinical characteristics, biological variables, and renal pathologic findings.

Rituximab will be administered as two injections separated by one week at a dose of 375 mg/m², with definitive steroid withdrawal after 9 weeks of treatment. The trial will follow participants for 12 months to monitor the primary endpoint and for 18 months to assess secondary endpoints. The study aims to demonstrate the efficacy of Rituximab in preventing relapse in MCNS patients once complete remission is achieved.