Study Evaluating Etanercept in Subjects With Ankylosing Spondylitis in Spain

Study Overview
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Brief Summary
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The purpose of this study was to evaluate efficacy and safety of etanercept 100 mg (50 mg twice a week) compared with 50 mg once a week in adult subjects with ankylosing spondylitis (AS) and previous failure to usual practice therapies in Spain.

Official Title
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A 12-week Randomized, Double-blind, Multicenter Pilot Study to Evaluate the Effect of Etanercept 100 mg and 50 mg Weekly in Subjects With Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: etanercept
* Drug: etanercept/placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of ankylosing spondylitis, as defined by Modified New York Criteria for Ankylosing Spondylitis. Maintained inflammatory activity for more than 12 weeks defined by:·Axial forms: BASDAI higher than or equal to 4 (0-10) and at least one of the following parameters:. Global assessment of the disease by the patient higher than or equal to 4 (On a scale 0-10). Spinal pain higher than or equal to 4 on a visual analogue scale (VAS). Increase in erythrocyte sedimentation rate (ESR) and/or CRP above the normality parameters established by the laboratory.·Peripheral forms: Arthritis or enthesitis higher than or equal to 1 site and at least one of the following:. Global assessment of the disease by the patient higher than or equal to 4 (on a scale 0-10). Increase in erythrocyte sedimentation rate (ESR) and/or CRP above the normality parameters established by the laboratory Failure to treatment: Failure to at least 2 NSAIDs at maximum recommended dose during at least 3 months (or a shorter time in case of intolerance, toxicity or contraindication).·In cases of ankylosing spondylitis with peripheral joint involvement, salazopyrine should have been used at a dose of 2-3 g per day and/or methotrexate (15 mg/week) for 4 months (or a shorter time in case of intolerance, toxicity or contraindication). In case of oligoarticular or localized involvement in enthesis: lack of response, at the discretion of the investigator, to local infiltrations and/or synoviorthesis. Be between 18-70 years of age Negative result of a pregnancy test in serum in screening visit and in urine in baseline visit, done in all women, except those surgically sterilized and those who have at least one year of menopause. Sexually active women of childbearing potential must use medically acceptable contraceptive methods, including oral, injectable or implantable contraceptive methods, intrauterine devices or properly used barrier contraception. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Men who are not surgically sterile should agree to use reliable contraceptive methods during the study. Ability to reconstitute the drug and self-inject it or have a person who can do so. Capability to understand and voluntarily give written informed consent that is signed and dated, before any specific procedure of the protocol is performed. Ability to store injectable test article at 2º to 8º C. Exclusion criteria: Contraindications for treatment with anti-TNF Complete ankylosis of spine Onset of treatment with DMARDs in the 4 weeks prior to baseline (SSZ, MTX and HCQ are permitted if the administrated dose has been maintained stable in the 4 weeks prior to baseline). Furthermore, patients with a dose of prednisone >10 mg/d or equivalent or modified in the 2 weeks prior to the baseline visit, those in whose infiltration has been performed with intraarticular corticosteroids has been performed in the 4 weeks prior to the screening visit and those who follow treatment with more than one NSAID in the 2 weeks prior to the baseline visit are excluded. Previous treatment with other TNF inhibitors and other biological drugs Abnormalities in hematology profiles defined by: leukocytes lower than or equal to 3.5 x 10 exponent 9 /L hemoglobin lower than or equal to 8.5 g/L or 5.3 mmol/L hematocrit lower than or equal to 27% platelets lower than or equal to 125 x 10 exponent 9 /L serum creatinine higher than or equal to 175 mmol/L aspartate aminotransferase and alanine aminotransferase higher than or equal to 2 times the upper limit of normality Important concomitant medical conditions, such as:-Class III or IV congestive heart failure according to New York Heart Association classification-Uncontrolled arterial hypertension (defined as screening systolic blood pressure > 160 mm Hg or screening diastolic blood pressure > 100 mm Hg)-Myocardial infarction within 12 months of the screening visit or unstable angina-Severe pulmonary disease requiring hospitalization or oxygen therapy-Diagnosis of multiple sclerosis or other central nervous system demyelinating disease -Presence or history of confirmed blood dyscrasias-Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma)-Serious infection (infection requiring hospitalization and/or intravenous antibiotics) within 1 month of administration of test article administration or active infection at screening or history of recurrent or chronic infection-Open cutaneous ulcers-Patients with known chronic infections as positivity to HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) -Active tuberculosis infection (local guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF therapy must be followed)- Any condition that, in the investigator's judgment, might cause this study to be detrimental to the subject Pregnant or breast-feeding women Past or current psychiatric illness that would interfere with the subject's ability to comply with protocol requirements or give informed consent. Treatment with any live (attenuated) vaccine within 4 weeks prior to baseline. History of alcohol or drug abuse that would interfere with the subject's ability to comply with protocol requirements. Treatment with any investigational drug within 3 months of screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: etanercept<br>* Etanercept 50 mg twice a week (BIW) for 12 weeks<br>|
| Active Comparator: 2<br> | Drug: etanercept/placebo<br>* Etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 20. | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute change ≥ 10 units on a 0-100 scale (0=no disease activity; 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 40. | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain. | 12 weeks | 
| Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 50. | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain. | 12 weeks | 
| Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 70. | ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain. | 12 weeks | 
| Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6. | ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (patient global assessment of disease activity, pain, function, inflammation measured on a 0-100 scale, where 0=no disease activity, 100=high disease activity) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains and no worsening in the remaining domain. | 12 weeks | 
| Number of Patients Achieving Partial Remission. | Partial remission defined as a score of less than 20 units (on a scale of 0-100, where 0=no disease activity, 100=high disease activity) in each of the 4 Assessment in Ankylosing Spondylitis (ASAS) domains: patient global assessment of disease activity, pain, function, and inflammation. For scale, 100=high disease activity. | 12 weeks | 
| Change in Nocturnal Back and Overall Spinal Pain From Baseline to Week 12. | Nocturnal back and overall spinal pain assessed by patients using a Visual Analog Scale (VAS) of 0 - 10 (0 = no pain and 10 = most severe pain). | Baseline and 12 weeks | 
| Change in Physician and Patient Global Assessment (PGA) of Pain From Baseline to Week 12. | Patient pain assessed by physician and patient using a Visual Analog Scale (VAS) of 0 - 10 (0 = none and 10 = severe). | Baseline and 12 weeks | 
| Change in Bath Ankylosing Spondylitis Functional Index (BASFI) From Baseline to Week 12. | BASFI is a validated self assessment tool that determines the degree of functional limitation in AS patients. Utilizing a VAS of 0-10 (0=easy, 10=impossible), patients answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions. | Baseline and 12 weeks | 
| Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) From Baseline to Week 12. | BASDAI is a validated self assessment tool used to determine disease activity in patients with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments. | Baseline and 12 weeks | 
| Change in Bath Ankylosing Spondylitis Metrology Index (BASMI) From Baseline to Week 12. | BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. | Baseline and 12 weeks | 
| Change in Erythrocyte Sedimentation Rate (ESR) From Baseline to Week 12. | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube and is measured in mm/hour. Normal range is 0-30mm/h. A higher rate is consistent with inflammation. | Baseline and 12 weeks | 
| Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire | EuroQol questionnaire is intended to measure the quality of life by means of questions about mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Answers to every question were grouped in two main categories: with problems (having some problems or absolutely unable) or without problems. | 12 weeks | 
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). | Baseline and 12 weeks | 
| Improvement of Ocular Inflammatory Disease in Patients With Baseline Symptoms |  | 12 weeks | 
| Change in C-reactive Protein (CRP) From Baseline to Week 12. | CRP is a marker of inflammation and measured in mg/l. A higher level is consistent with inflammation. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect of etanercept in subjects with ankylosing spondylitis