NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis

Study Overview
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Brief Summary
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To evaluate the impact of treatment with a non-steroidal anti-inflammatory drug (NSAID) - Celecoxib - when added to anti-tumour necrosis factor (TNF) therapy - Golimumab - as compared to anti-TNF therapy (Golimumab) alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS).

Detailed Description
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The aim of the proposed trial is to evaluate the efficacy of combined treatment with a non-steroidal anti-inflammatory drug (NSAID) added to anti-tumour necrosis factor (TNF) therapy as compared to anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS). The trial consists of two phases. In the phase I (run-in phase), patients with active AS despite treatment with NSAIDs and elevated C-reactive protein will be included and treated with a TNF blocker (golimumab). Patients with good clinical response to golimumab at week 12 will be eligible for the phase II (core phase) of the study and will be randomized 1:1 to 1) golimumab + celecoxib (experimental intervention) for 2 years (weeks 12-108) or 2) golimumab alone (control intervention) also for 2 years. The primary outcome parameter will be the absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) - currently a standard of structural spinal damage progression evaluation in AS - over two years of therapy (weeks 12-108).

Official Title
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COmparison of the Effect of Treatment With NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of StrUctural Damage in the Spine Over Two Years in Patients With ankyLosing Spondylitis: a Randomized Controlled Multicentre Trial

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Biological: Golimumab
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Definite diagnosis of AS according to the modified New York criteria. History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each. Active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value of ≥4 at screening. Presence of at least one of the following risk factors for radiographic spinal progression: Elevated C reactive protein (CRP; >5mg/l) at screening at the absence of reasons for elevated CRP other than AS; Presence of ≥ 1 syndesmophyte on prior X-rays of the spine. Subject is a candidate for anti-TNF therapy based on the Investigator's opinion. Subject is able and willing to give a written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial. If female: either unable to bear children (postmenopausal for at least 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception throughout the study and 6 months after Inclusion Criterion for Phase II (randomized part of the study): - adequate response to Golimumab during Phase I (referred to as decline in BASDAI) Major Exclusion Criteria: For female subjects: pregnancy or lactating subjects with chronic inflammatory articular disease other than spondyloarthritis / AS or systemic autoimmune disease, e.g. systemic lupus erythematosus, Sjögren´s syndrome, rheumatoid arthritis. history of inadequate response to anti-TNF-therapy intolerability/hypersensitivity to one of the drugs or other components of the study medication presence ot total spinal ankylosis contraindications to anti-TNF-therapy (current or remitting clinical significant infections, tuberculosis, viral hepatitis, HIV; malignancies; demyelinating disease; vaccination with live vaccine within 3 months before, during and until 6 months after study) (relative) contraindications to Celecoxib therapy (uncontrolled arterial hypertension, high cardiovascular risk / history of cardiovascular events; history of gastrointestinal ulcers or relevant bleeding; known M. Crohn or ulcerative colitis) diagnosis of fibromyalgia significant lab abnormalities

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Golimumab monotherapy<br>Treatment with 50 mg Golimumab subcutaneous once monthly | Biological: Golimumab<br> <br> * Other names: Simponi;|
| Active Comparator: Golimumab combined with Celecoxib<br>Treatment with Golimumab 50 mg subcutaneous once monthly in combination with Celecoxib 400 mg orally every day | Biological: Golimumab<br> <br> * Other names: Simponi;Drug: Celecoxib<br> <br> * Other names: Celebrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial | Absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) over two years of therapy (weeks 12-108) in the Phase II (core phase) of the trial | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New syndesmophyte formation or progression of existing syndesmophytes | New syndesmophyte formation or progression of existing syndesmophytes | 2 years | 
| Improvement of disease activity (BASDAI) | Improvement of disease activity (BASDAI) | 2 years | 
| Improvement of disease activity (ASDAS) | Improvement of disease activity (ASDAS) | 2 years | 
| Improvement of function (BASFI) | Improvement of function (BASFI) | 2 years | 
| Improvement of axial mobility (BASMI) | Improvement of axial mobility (BASMI) | 2 years | 
| Improvement of quality of life measures (ASAS Health Index) | Improvement of quality of life measures (ASAS Health Index) | 2 years | 
| Change of the enteric microbiome profile at week 108 in comparison to baseline | Change of the enteric microbiome profile at week 108 in comparison to baseline | 2 years | 
| Change of Berlin MRI score (SUBSTUDY) | Change of Berlin MRI score (SUBSTUDY) | 2 years | 
| Adverse events (AE), serious AE and AE of interest until end of study | Adverse events (AE), serious AE and AE of interest until end of study | 2 years |