Study of the Efficacy and Safety of Etanercept Treatment in Patients With SAPHO Syndrome

Study Overview
=================
Brief Summary
-----------------
The study includes adult patients with SAPHO syndrome (ORPHA: 793), meeting the modified classification criteria according to Kahn (2003), with the ineffectiveness of standard treatment (patient's global assessment of the disease on the VAS scale greater than or equal to 4 cm with accompanying pain on the VAS scale greater than or equal to 4 cm) treated with non-steroidal anti-inflammatory drugs in a stable dose for at least 4 weeks and/or classical disease-modifying antirheumatic drugs in stable doses for at least 12 weeks.

Official Title
-----------------
A Multicenter, Randomized, Double-blind Clinical Trial Evaluating the Efficacy and Safety of Etanercept Versus Placebo in the Treatment of Patients With SAPHO Syndrome

Conditions
-----------------
SAPHO Syndrome

Intervention / Treatment
-----------------
* Drug: Etanercept
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of SAPHO syndrome according to modified Kahn criteria from 2003. Age over 18. Patient overall disease and pain assessment on VAS both ≥ 4 cm. Expressing informed consent to participate in the study. Exclusion Criteria: According to the Summary of Product Characteristics (SmPC) for Enbrel. Pregnancy, breastfeeding, inability to use effective contraception during the examination. Change in the dose of NSAIDs treatment in the last 4 weeks. Dose modification of disease-modifying antirheumatic drugs (DMARDs) over the past 12 weeks. Use of biological drugs / synthetic targeted drugs in the last 12 weeks. Use of corticosteroids (orally or local injections), bisphosphonates and/or antibiotics in the last 4 weeks. Any medical condition that the investigator judges to contraindicate etanercept treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept<br>treatment with etanercept in addition to NSAID treatment and/or classic Disease Modifying Antirheumatic Drugs | Drug: Etanercept<br>* treatment with etanercept in addition to NSAID treatment and/or classic Disease Modifying Antirheumatic Drugs<br>|
| Placebo Comparator: Placebo<br>treatment with placeboin addition to NSAID treatment and/or classic Disease Modifying Antirheumatic Drugs | Drug: Placebo<br>* treatment with placebo in addition to NSAID treatment and/or classic Disease Modifying Antirheumatic Drugs<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the scope of disease activity as assessed by the patient- a decrease in the overall disease activity on the Visual Analogue Scale by min. 50 percent and a decrease in pain assessed by the patient on the Visual Analogue Scale by min. 50 percent | Change in the scope of disease activity as assessed by the patient - a decrease in the overall disease activity as assessed by the patient on the Visual Analogue Scale by min. 50 percent after 12 weeks from randomization day and a decrease in pain assessed by the patient on the Visual Analogue Scale by min. 50 percent after 12 weeks from randomization day. The minimum value is - 0, and the maximum value is - 100 mm. The higher scores mean a worse outcome. A decrease by a minimum of 50 percent means a better outcome. | 12 weeks (day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient-assessed disease activity | Change in patient-assessed disease activity - a minimum 50 percent decrease in patient-assessed Visual Analogue Scale overall disease activity from the randomization score at weeks 4 and 8 and a minimum 50 percent decrease in patient-assessed Visual Analogue Scale pain from the score on daily basis randomization after 4 and 8 weeks. The minimum value is - 0, and the maximum is - 100 mm. The higher scores mean a worse outcome. A decrease by a minimum of 50 percent means a better outcome. | after 4 and 8 weeks | 
| Occurrence of remission | Occurrence of remission - complete resolution of osteoarticular and skin complaints in the patient's assessment - after 4, 8 and 12 weeks from randomization day | after 4, 8 and 12 weeks | 
| Occurrence of partial remission | Occurrence of partial remission - complete resolution of osteoarticular or skin symptoms in the patient's assessment - after 4, 8 and 12 weeks from randomization day | after 4, 8 and 12 weeks | 
| Occurrence of the patient acceptable symptom state (PASS score) | Occurrence of the patient acceptable symptom state (PASS score) after 4, 8 and 12 weeks from randomization day. Possible answer- yes or no, with yes means a better outcome. | after 4, 8 and 12 weeks | 
| Change in physician-assessed disease activity | Improvement in physician-assessed disease activity - a minimum 50 percent decrease in physician-assessed overall disease activity on the Visual Analogue Scale from the randomization score at 4, 8 and 12 weeks. The minimum value is - 0, and the maximum is - 100 mm. The higher scores mean a worse outcome. A decrease by a minimum of 50 percent means a better outcome. | at 4, 8 and 12 week | 
| Change in the C-reactive Protein from Randomization Day Score | Change in C-reactive Protein from Randomization Day Score at Weeks 4, 8 and 12. A decrease in C-reactive Protein means improvement. | at Weeks 4, 8 and 12 | 
| Change in the Erythrocyte Sedimentation Rate from Randomization Day Score | Change in the Erythrocyte Sedimentation Rate Score from Randomization Day Score at Weeks 4, 8 and 12. A decrease in the Erythrocyte Sedimentation Rate Score means improvement. | at Weeks 4, 8 and 12 | 
| Change in quality of life on the Short Form-36 health survey | Change in quality of life on the Short Form -36 (SF-36) health survey from the score on the day of randomization at 4, 8 and 12 weeks. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. | at 4, 8 and 12 weeks | 
| Change in the Work Productivity and Activity Impairments (WPAI) from the Randomization Day Score | Change in the Work Productivity and Activity Impairments (WPAI) from the Randomization Day Score after 4, 8 and 12 weeks. WPAI contains four domains. For each domain, the minimum value is 0 percent, and the maximum is 100 percent. Decreased Work Productivity and Activity Impairments (WPAI) Score means improvement. | after 4, 8 and 12 weeks | 
| decrease in Ankylosing Spondylitis Disease Activity Score (ASDAS- C-reactive protein) ≥1.1 | In patients with axial involvement, a decrease in Ankylosing Spondylitis Disease Activity Score (ASDAS- C-reactive protein) ≥1.1 from the Randomization Day Score at weeks 4, 8, and 12. The minimum value is 0, the maximum value is infinity. A decrease means a better outcome. | after 4, 8 and 12 weeks | 
| a decrease in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score of at least 50 percent | a decrease in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score of at least 50 percent from the Randomization Day Score at weeks 4, 8, and 12 was achieved (applies to patients with axial involvement). The minimum value is 0, the maximum value is 10. A decrease by a minimum of 50 percent means a better outcome. | after 4, 8 and 12 weeks | 
| status of remission- Ankylosing Spondylitis Disease Activity Score (ASDAS- C-reactive protein) below 1.3 | status of remission - Ankylosing Spondylitis Disease Activity Score (ASDAS- C-reactive protein) below 1.3 - after 4, 8 and 12 weeks from randomization day (applies to patients with axial involvement). A score below 1.3 means a better outcome. | after 4, 8 and 12 weeks | 
| decrease in the Bath Ankylosing Spondylitis Functional Index (BASFI) by a minimum of 50 percent | a decrease in the Bath Ankylosing Spondylitis Functional Index (BASFI) by a minimum of 50 percent compared to the result on the day of randomization after 4, 8 and 12 weeks (applies to patients with axial involvement). The minimum value is 0, the maximum value is 10. A decrease by a minimum of 50 percent means a better outcome. | after 4, 8 and 12 weeks | 
| decrease in the Dermatology Life Quality Index (DLQI) by at least 50 percent from the result on the day of randomization | In patients with severe acne - a decrease in the Dermatology Life Quality Index (DLQI) by at least 50 percent from the result on the day of randomization after 4, 8 and 12 weeks. The minimum value is 0, the maximum value is 30. The decrease by a minimum of 50 percent means a better outcome. | after 4, 8 and 12 weeks | 
| decrease in Body Surface Area (BSA) index by a minimum of 50 percent from the score on the day of randomization after 4, 8 and 12 weeks | For patients with psoriasis: decrease in Body Surface Area (BSA) index by a minimum of 50 percent from the score on the day of randomization after 4, 8 and 12 weeks. The minimum value is 0 percent, and the maximum value is 100 percent. The decrease by a minimum of 50 percent means a better outcome. | after 4, 8 and 12 weeks | 
| decrease in the Dermatology Life Quality Index (DLQI) by a minimum of 50 percent | For patients with psoriasis: decrease in the Dermatology Life Quality Index (DLQI) by a minimum of 50 percent from the score on the day of randomization after 4, 8 and 12 weeks. The minimum value is 0, the maximum value is 30. The decrease by a minimum of 50 percent means a better outcome. | after 4, 8 and 12 weeks |