Efficacy of Golimumab in Early Axial Spondyloarthritis in Relation to Gut Inflammation

NCT03270501 | Completed Phase 3 Results

• 1 other identifier: GO-GUT trial
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

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.

Conditions

Axial Spondyloarthritis

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Achieving Sustained Clinical Remission

  The proportion of patients who completed the trial and achieved Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) \< 1.3 recorded on 2 consecutive visits with at least 12 weeks interval. ASDAS-CRP was measured at every study visit, i.e. baseline, week 2, week 4, week 16, week 28, week 40 and week 52. The study endpoint could earliest be achieved at visit week 28.

  Upon end of trial for individual patient, between 28 and 52 weeks.

Secondary Outcomes (1)

• The Proportion of Patients With Healed Lesions of the Intestinal Mucosa

  At reaching primary outcome (between week 24 and week 52)

Study Arms (1)

Arm 1: Golimumab

EXPERIMENTAL

Drug: Golimumab

Interventions

Golimumab DRUG

Axial spondyloarthritis patients who don't have a good treatment response on 2 NSAIDs, will be treated with golimumab. After remission, the therapy will be stopped. All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission.

Also known as: ileocoloscopy

Arm 1: Golimumab

Eligibility Criteria

• Age: 18 Years - 46 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Ghent: lead
• Merck Sharp & Dohme LLC: collaborator
• the Flanders Institute for Biotechnology: collaborator

Study Sites (3)

Imelda Bonheiden

Bonheiden, Antwerpen, 2820, Belgium

Location

Ghent University Hospital

Ghent, B - Belgium, 9000, Belgium

Location

Reuma Instituut Hasselt

Hasselt, Limburg, 3500, Belgium

Location

Related Publications (3)

• Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011 Jun 18;377(9783):2127-37. doi: 10.1016/S0140-6736(11)60071-8.

  PMID: 21684383 BACKGROUND

• 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.

  PMID: 3875721 BACKGROUND

• 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.

  PMID: 23139267 BACKGROUND

MeSH Terms

Conditions

Axial Spondyloarthritis

Interventions

golimumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Limitations and Caveats

The trial included 64 of initially anticipated 147 patients, which impacts downstream analyses which were powered for a larger group. The baseline prevalence of gut inflammation in the studied patient population was lower than anticipated. Therefore primary objective of the study (to evaluate whether there is a higher need of anti-TNFα treatment in patients with gut inflammation compared to those without) could not be adressed.

Results Point of Contact

• Title: Professor Dirk Elewaut
• Organization: Department of Rheumatology, Gent University Hospital

reumatologie@uzgent.be

+32 9 332 22 30

Study Officials

• Dirk Elewaut

  University Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: September 1, 2017
• Study Start: November 8, 2017
• Primary Completion: December 14, 2023
• Study Completion: December 14, 2023
• Last Updated: February 11, 2025
• Results First Posted: February 11, 2025

Record last verified: 2024-07

Locations

BE (3)