Prospective Multicenter Study on Early Discontinuation of Prednisolone in FDG-PET/CT Negative Patients with Idiopathic Retroperitoneal Fibrosis

The primary objective of this study is to compare the cumulative relapse rate of **idiopathic retroperitoneal fibrosis** (IRF) 12 months after the discontinuation of steroid treatment. This is clinically relevant as it aims to evaluate the potential for reducing long-term steroid use, which can have significant side effects, in patients who show negative results on FDG-PET/CT scans.

Secondary objectives include:

• Analyzing the characteristics of hypermetabolism of IRF in FDG-PET/CT and their evolution at diagnosis, remission (M9), M21, and relapse.
• Assessing the performance of hypermetabolism of IRF in FDG-PET/CT for diagnosing disease activity.
• Comparing at M21 the corticosteroid therapy-related adverse events between patients who continue or discontinue the treatment at M9.

The clinical trial focuses on patients diagnosed with **idiopathic retroperitoneal fibrosis** (IRF). The study population includes both male and female participants, all of whom are over the age of 18. The trial does not involve a vulnerable population. Participants were selected based on the presence of new onset or untreated relapsing active IRF, characterized by related-disease symptoms or an elevated C-reactive protein (CRP) level greater than 20 mg/l, in conjunction with a retroperitoneal peri-aortic mass surrounding the abdominal vessels as observed on a CT scan. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The trial aims to compare the cumulative IRF relapse rate 12 months after the discontinuation of steroids.

The clinical trial is designed to evaluate the **cumulative relapse rate** of idiopathic retroperitoneal fibrosis (IRF) 12 months after the discontinuation of steroid treatment. This study is a prospective, multicentric, randomized, double-blind, controlled trial. The trial is expected to run from November 2022 to September 2027, with a total duration of approximately five years. Participants will be involved for a maximum of 21 months, with the treatment period lasting up to 9 months. The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit.

The screening visit will determine eligibility based on criteria such as age (over 18 years) and the presence of new onset or untreated relapsing active IRF, characterized by related symptoms or elevated CRP levels and a retroperitoneal peri-aortic mass on CT-scan. Follow-up visits will occur at specified intervals to monitor the primary endpoint, which is the cumulative IRF relapse rate at the end of the study (M21). Secondary endpoints include the assessment of visual grades of retroperitoneal fibrosis FDG uptake, diagnostic performance of SUVmax and MAV, and the frequency of diabetes, severe infection, osteoporotic fracture, and major cardiovascular events 12 months after remission.

Participants will be administered **prednisolone** orally, with a maximum daily dose of 80 mg and a total dose not exceeding 7644 mg. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial aims to provide valuable insights into the management of IRF and the potential for early discontinuation of steroid treatment in patients with negative FDG-PET/CT results.

The clinical trial involves the administration of **PREDNISONE**, a synthetic glucocorticoid, as the experimental medication. The active substance in this formulation is **prednisolone**, a chemical compound known for its anti-inflammatory and immunosuppressive properties. The pharmaceutical form of the medication is designated as PHF00245MIG, and it is administered orally. The maximum daily dose is 80 mg, with a total maximum dose of 7644 mg over the course of the treatment. The treatment period is limited to a maximum of 9 months. The medication is not formulated specifically for pediatric use, and it is not classified as an orphan drug. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The primary objective of the trial is to evaluate the cumulative relapse rate of idiopathic retroperitoneal fibrosis (IRF) 12 months after the discontinuation of steroid treatment in patients who test negative on FDG-PET/CT scans. The trial is designed to assess the efficacy of early steroid discontinuation in this patient population. Compliance with the dosing schedule is critical, and participants are monitored throughout the study to ensure accurate data collection and analysis.

Efficacy in this clinical trial will be assessed primarily through the cumulative relapse rate of **idiopathic retroperitoneal fibrosis (IRF)**, measured at the end of the study period, which is 21 months (M21). The diagnosis of IRF relapse will be based on a composite criterion that includes both clinical or biological indicators and radiological evidence. Secondary endpoints will include several parameters: visual grades of retroperitoneal fibrosis FDG uptake compared to liver FDG uptake, with scores ranging from 0 to III, and the maximal standardized uptake value (SUVmax) within the retroperitoneal fibrosis regions of interest (ROI) at various timepoints—diagnosis (M0), remission (M9), M21, and relapse. Additionally, the metabolic volume, defined as the ratio of metabolically active volume (MAV) to global lesion volume, will be evaluated at the same timepoints.

The diagnostic performance of SUVmax and MAV will be analyzed using the area under the curve (AUC) and performance values for the Youden index to assess disease activity. Furthermore, the frequency of diabetes, severe infection, osteoporotic fracture, and major cardiovascular events will be monitored 12 months after remission (M21). Serious cardiovascular adverse events, defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death, will be assessed at M12, M15, and M21. These efficacy parameters will be collected and analyzed using validated scales and laboratory tests at specified intervals throughout the trial.