Clinical trial NCT02758782: NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2016-05-02
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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:

  1. Elevated C reactive protein (CRP; \>5mg/l) at screening at the absence of reasons for elevated CRP other than AS;
  2. 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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: New syndesmophyte formation or progression of existing syndesmophytes
timeFrame: 2 years
measure: Improvement of disease activity (BASDAI)
timeFrame: 2 years
measure: Improvement of disease activity (ASDAS)
timeFrame: 2 years
measure: Improvement of function (BASFI)
timeFrame: 2 years
measure: Improvement of axial mobility (BASMI)
timeFrame: 2 years
measure: Improvement of quality of life measures (ASAS Health Index)
timeFrame: 2 years
measure: Change of the enteric microbiome profile at week 108 in comparison to baseline
timeFrame: 2 years
measure: Change of Berlin MRI score (SUBSTUDY)
timeFrame: 2 years
measure: Adverse events (AE), serious AE and AE of interest until end of study
timeFrame: 2 years
Other outcomes:
Locations:
city: Altenburg
country: Germany
facility: Rheumapraxis Kupka
city: Bayreuth
country: Germany
facility: Rheumapraxis Bayreuth Dr. Ochs
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin - Dpt. Rheumatology at Campus Charite Mitte
city: Berlin
country: Germany
facility: Rheumatologische Schwerpunktpraxis
city: Berlin
country: Germany
facility: Rheumatologische Praxis Dr. Karberg/Brandt
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin, Dpt. of Rheumatology at Campus Benjamin Franklin
city: Berlin
country: Germany
facility: MVZ Drs. Mielke
city: Berlin
country: Germany
facility: Rheumapraxis Dr. Zinke
city: Berlin
country: Germany
facility: Schlossparkklinik, Dpt. of Rheumatologie
city: Burghausen
country: Germany
facility: Rheumatologische Schwerpunktpraxis an den Kreiskliniken
city: Frankfurt / Main
country: Germany
facility: Centrum für innovative Diagnostik und Therapie Rheumatologie/Immunologie (CIRI)
city: Haldensleben I
country: Germany
facility: Praxis Dr Kühne
city: Hannover
country: Germany
facility: Medizinische Hochschule, Rheumatologie
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Koeln
country: Germany
facility: Universitätsklinikum Köln, Rheumatologie
city: Magdeburg
country: Germany
facility: Rheumapraxis Magdeburg
city: München
country: Germany
facility: Klinikum Rechts der ISAR (TU München)
city: Tübingen
country: Germany
facility: Rheumapraxis Dr. Jacki
city: Tübingen
country: Germany
facility: University of Tuebingen, Dpt. Rheumatology
Study officials:
affiliation: Head of Dpt. for Rheumatology at Charite, Campus Benjamin Franklin
name: Denis Poddubnyy, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Proft F, Muche B, Listing J, Rios-Rodriguez V, Sieper J, Poddubnyy D. Study protocol: COmparison of the effect of treatment with Nonsteroidal anti-inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a therapy alone on progression of StrUctural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) - an open-label randomized controlled multicenter trial. BMJ Open. 2017 Jun 10;7(6):e014591. doi: 10.1136/bmjopen-2016-014591.