Efficacy and Safety Evaluation of Etanercept Versus Placebo in SAPHO Syndrome Patients Undergoing Standard NSAID and DMARD Therapy

The primary objective of this multicenter, randomized, double-blind clinical trial is to evaluate the **efficacy** and **safety** of **etanercept** therapy compared to placebo in patients with SAPHO syndrome who continue to receive standard treatment with NSAIDs and/or conventional disease-modifying antirheumatic drugs. This is clinically relevant as SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis, significantly reduces the quality of life due to chronic pain and limited daily activity. The trial aims to determine if etanercept can provide a more effective treatment option, potentially improving patient outcomes and quality of life.

Secondary objectives include increasing the access of patients with SAPHO syndrome to modern forms of treatment, specifically through the use of the biological drug etanercept, which has been previously unavailable to them. This objective addresses the need for more accessible and advanced therapeutic options for this rare and debilitating condition.

The clinical trial involves participants diagnosed with **SAPHO syndrome**, a rare condition characterized by arthritis, osteitis, and skin lesions such as pustular psoriasis or acne. The study population includes both male and female subjects over the age of 18, with no specific upper age limit mentioned. Participants are required to have a patient overall disease and pain assessment on the Visual Analogue Scale (VAS) of 4 cm or greater. The trial does not specify the total number of participants, as the sponsor has not provided this information. The selection criteria include a diagnosis according to the modified Kahn criteria from 2003 and the ability to provide informed consent. The trial population is inclusive of a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed. The study aims to evaluate the efficacy and safety of etanercept therapy compared to placebo in patients who continue to receive standard treatment with NSAIDs and/or conventional disease-modifying antirheumatic drugs.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of **etanercept** compared to placebo in patients diagnosed with SAPHO syndrome. The trial will involve participants who continue to receive standard treatment with NSAIDs and/or conventional disease-modifying antirheumatic drugs. The study is expected to run until July 31, 2028, with recruitment having commenced on May 4, 2023. The trial will include several key phases, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of SAPHO syndrome according to modified Kahn criteria from 2003, age over 18, and a patient overall disease and pain assessment on VAS both ≥ 4 cm. Participants must also provide informed consent to participate in the study.

Following the screening, eligible participants will be randomly assigned to receive either etanercept or placebo, administered via **subcutaneous use**. The maximum daily dose of etanercept is 50 mg, with a treatment period of up to 36 months for some formulations. The primary endpoint of the study is to observe an improvement in disease activity, specifically a decrease in overall disease activity and pain as assessed by the patient on the VAS scale by a minimum of 50% after 12 weeks. Participants will attend regular follow-up visits to monitor their response to treatment and any adverse effects. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the long-term efficacy and safety of the treatment.

The expected length of participant involvement varies depending on the formulation of etanercept administered, with some participants involved for up to 36 months. Conditions that may lead to early termination from the study include significant adverse reactions, withdrawal of consent, or non-compliance with study protocols. The trial aims to provide valuable insights into the potential benefits of etanercept for patients with SAPHO syndrome, contributing to the understanding and management of this rare condition.

The clinical trial involves the administration of **etanercept**, a biologic medication, in various formulations. The primary experimental treatment is "Enbrel 25 mg powder and solvent for solution for injection," which is reconstituted to form a **solution for injection**. This formulation is administered via **subcutaneous use**. The maximum daily dose is 50 mg, with a total dose not exceeding 50 mg per day. The treatment period for this formulation is up to 12 weeks. The active substance, etanercept, is a protein derived from a non-chemical origin, specifically classified as "Protein - Other." The pharmaceutical form is a powder and solvent combination, requiring preparation before administration.

Another formulation used in the trial is "Enbrel 50 mg solution for injection in pre-filled syringe." This formulation is also administered via **subcutaneous use**. The maximum daily dose is 50 mg, with a total dose not exceeding 50 mg per day. The treatment period for this formulation extends up to 36 weeks. The active substance remains etanercept, with the same protein origin classification. This formulation is provided as a ready-to-use solution in a pre-filled syringe, facilitating ease of administration.

The trial also includes a placebo control, "WATER FOR INJECTIONS," which serves as a comparator treatment. This placebo is administered as a **solution for injection or infusion** via **subcutaneous use**. The maximum daily dose is 2 ml, with a total dose not exceeding 2 ml per day. The treatment period for the placebo is up to 12 weeks. The active substance in the placebo is chemically derived water, ensuring no therapeutic effect, thus serving as a control to evaluate the efficacy of etanercept.

Throughout the trial, participant compliance is monitored through regular assessments and documentation of dosing schedules. The trial aims to evaluate the efficacy and safety of etanercept in patients with SAPHO syndrome, who continue to receive standard treatment with NSAIDs and/or conventional disease-modifying antirheumatic drugs. The trial is conducted under a double-blind, randomized, multicenter design to ensure the reliability and validity of the results.

The efficacy of the clinical trial will be assessed by evaluating the improvement in disease activity in patients with SAPHO syndrome. The primary endpoint for efficacy is defined as a decrease in overall disease activity and pain, as assessed by the patient using the Visual Analogue Scale (VAS). Specifically, a minimum 50% reduction in both overall disease activity and pain on the VAS scale after 12 weeks of treatment will be considered indicative of efficacy. The VAS is a validated tool commonly used for patient-reported outcomes in clinical trials, providing a quantitative measure of symptom severity.