Clinical trial NCT03270501: Efficacy of Golimumab in Early Axial Spondyloarthritis in Relation to Gut Inflammation
Official title: Efficacy of Golimumab in Early Axial Spondyloarthritis in Relation to Gut Inflammation, an Early Remission Induction Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: the Flanders Institute for Biotechnology
First posted: 2017-09-01
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The hypothesis of the study is that the presence of (subclinical) gut inflammation at baseline in patients with early active axial spondyloarthritis predisposes to a more severe disease defined as more need to use anti-tumor necrosis factor α therapy and a shorter time to relapse after stopping anti-tumor necrosis factor α therapy after obtaining sustained clinical remission. Overall, the investigators hypothesize that subclinical gut inflammation is an important predictor in therapy response and outcome. These data could provide better insights into the complex interactions between gut and joint inflammation and guide the physicians in the therapeutic approach.


Eligibility criteria: Inclusion Criteria:

* Subject must have a diagnosis of axSpA and classified according to ASAS criteria.
* Subject has at least 3 months and maximum 1 year (almost) daily chronic back pain.
* Subject has an active disease defined as a positive MRI (according to ASAS definition) or elevated CRP (in patients who are HLA-B27+) and an ASDAS score \> 2.1 (at least high disease activity).

Exclusion Criteria:

* Full anti-inflammatory dose of NSAIDs for more than 4 weeks for the duration of the axSpA symptoms.
* Prior exposure to any biologic therapy with a potential therapeutic impact on SpA, including anti-TNF therapy.
* Exposure to disease-modifying drugs (DMARDSs; i.e. methotrexate and sulfasalazine) in the last 3 months before the ileocolonoscopy.
* Exposure to systemic corticosteroid treatment in the last 14 days before the ileocolonoscopy.
* Infection(s) requiring treatment with intravenous antibiotics/antivirals/antifungals within 30 days prior to the baseline visit or oral antibiotics/antivirals/antifungals within 14 days prior to the baseline visit.
* Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.
* History of central nervous system (CNS) demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease.
* History of listeriosis, histoplasmosis, chronic of active hepatitis B infection, hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis.
* Have a history of, or concurrent, chronic heart failure, including medically controlled, asymptomatic congestive heart failure.
* Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
* Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of study agent.
* Positive pregnancy test at screening.
* Female subjects who are breast-feeding or considering becoming pregnant during the study.
* Female subjects who do not use contraceptives.
* History of clinically significant drug or alcohol abuse in the last 12 months.
* Clinically significant abnormal screening laboratory results as evaluated by the investigator.
* Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of the normal.
* Subject with diagnosis and current symptoms of fibromyalgia.
* Any medical or psychological condition that, in the opinion of the investigator, could jeopardize or compromise the subject's ability to participate in this study.

Primary outcomes:
measure: Proportion of Patients Achieving Sustained Clinical Remission
timeFrame: Upon end of trial for individual patient, between 28 and 52 weeks.
Secondary outcomes:
measure: The Proportion of Patients With Healed Lesions of the Intestinal Mucosa
timeFrame: At reaching primary outcome (between week 24 and week 52)
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Bonheiden
state: Antwerpen
city: Ghent
country: Belgium
facility: Ghent University Hospital
state: B - Belgium
city: Hasselt
country: Belgium
facility: Reuma Instituut Hasselt
state: Limburg
Study officials:
affiliation: University Ghent
name: Dirk Elewaut
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011 Jun 18;377(9783):2127-37. doi: 10.1016/S0140-6736(11)60071-8.
citation: Mielants H, Veys EM, Cuvelier C, De Vos M, Botelberghe L. HLA-B27 related arthritis and bowel inflammation. Part 2. Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol. 1985 Apr;12(2):294-8.
citation: Van Praet L, Van den Bosch FE, Jacques P, Carron P, Jans L, Colman R, Glorieus E, Peeters H, Mielants H, De Vos M, Cuvelier C, Elewaut D. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis. 2013 Mar;72(3):414-7. doi: 10.1136/annrheumdis-2012-202135. Epub 2012 Nov 8.