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

NCT ID: NCT02758782

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2021-01-31

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).

Conditions

Ankylosing Spondylitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Golimumab monotherapy

Treatment with 50 mg Golimumab subcutaneous once monthly

Group Type: ACTIVE_COMPARATOR

Golimumab

Intervention Type: BIOLOGICAL

Golimumab combined with Celecoxib

Treatment with Golimumab 50 mg subcutaneous once monthly in combination with Celecoxib 400 mg orally every day

Group Type: ACTIVE_COMPARATOR

Golimumab

Intervention Type: BIOLOGICAL

Celecoxib

Intervention Type: DRUG

Interventions

Golimumab

Intervention Type: BIOLOGICAL

Celecoxib

Intervention Type: DRUG

Other Intervention Names

Simponi; Celebrex

Eligibility Criteria

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Denis Poddubnyy

Prof Dr Denis Poddubnyy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Denis Poddubnyy, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Head of Dpt. for Rheumatology at Charite, Campus Benjamin Franklin

Locations

Rheumapraxis Kupka

Altenburg, , Germany

Rheumapraxis Bayreuth Dr. Ochs

Bayreuth, , Germany

Charite Universitaetsmedizin - Dpt. Rheumatology at Campus Charite Mitte

Berlin, , Germany

Rheumatologische Schwerpunktpraxis

Berlin, , Germany

Rheumatologische Praxis Dr. Karberg/Brandt

Berlin, , Germany

Charite Universitaetsmedizin, Dpt. of Rheumatology at Campus Benjamin Franklin

Berlin, , Germany

MVZ Drs. Mielke

Berlin, , Germany

Rheumapraxis Dr. Zinke

Berlin, , Germany

Schlossparkklinik, Dpt. of Rheumatologie

Berlin, , Germany

Rheumatologische Schwerpunktpraxis an den Kreiskliniken

Burghausen, , Germany

Universitätsklinikum Köln, Rheumatologie

Cologne, , Germany

Centrum für innovative Diagnostik und Therapie Rheumatologie/Immunologie (CIRI)

Frankfurt am Main, , Germany

Praxis Dr Kühne

Haldensleben I, , Germany

Medizinische Hochschule, Rheumatologie

Hanover, , Germany

Rheumazentrum Ruhrgebiet

Herne, , Germany

Rheumapraxis Magdeburg

Magdeburg, , Germany

Klinikum Rechts der ISAR (TU München)

München, , Germany

Rheumapraxis Dr. Jacki

Tübingen, , Germany

University of Tuebingen, Dpt. Rheumatology

Tübingen, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 28601821 (View on PubMed)

Other Identifiers

CONSUL2016

Identifier Type: -

Identifier Source: org_study_id