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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| the Flanders Institute for Biotechnology | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Golimumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| The Proportion of Patients With Healed Lesions of the Intestinal Mucosa | According to the protocol, every patient underwent ileocolonoscopy at baseline to screen for macroscopic and microscopic (histopathologic analysis of endoscopic biopsies) signs of inflammation. If baseline ileocolonoscopy was protocolled as positive, the patient would undergo a second ileocolonoscopic assessment at the timepoint of reaching sustained clinical remission (study endpoint). The outcome measure is the proportion of patients with a negative second ileocolonoscopy. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dirk Elewaut | University Ghent | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imelda Bonheiden | Bonheiden | Antwerpen | 2820 | Belgium | ||
| Ghent University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21684383 | Background | Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011 Jun 18;377(9783):2127-37. doi: 10.1016/S0140-6736(11)60071-8. | |
| 3875721 | 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. |
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Recruitment period: November 2017 - December 2022 across 3 centres:
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: NSAIDs With Possible Step-up to Golimumab | NSAIDs: All patients fulfilling the inclusion criteria will be treated according to the current recommendations for the management of axial spondyloarthritis, i.e. with 2 courses of NSAIDs. If sufficient response is acheived, the patients will continue receiving NSAIDs and after sustained remission, the therapy will be stopped. If therapy with NSAIDs provides insufficient control of disease activity, switch to therapy with Golimumab will be made. Golimumab: Patients who did not have a good treatment response to 2 NSAIDs, will be treated with golimumab sc 50mg/4 weeks. After sustained remission, the therapy will be stopped. All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients included in the trial and for whom the treatment protocol was initiated.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: NSAIDs With Possible Step-up to Golimumab | NSAIDs: All patients fulfilling the inclusion criteria will be treated according to the current recommendations for the management of axial spondyloarthritis, i.e. with 2 courses of NSAIDs. If sufficient response is acheived, the patients will continue receiving NSAIDs and after sustained remission, the therapy will be stopped. If therapy with NSAIDs provides insufficient control of disease activity, switch to therapy with Golimumab will be made. Golimumab: Patients who did not have a good treatment response to 2 NSAIDs, will be treated with golimumab sc 50mg/4 weeks. After sustained remission, the therapy will be stopped. All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Patients who completed the trial | Posted | Count of Participants | Participants | Upon end of trial for individual patient, between 28 and 52 weeks. |
|
Adverse events data was collected between the first dose administration of trial medication and the last trial related activity (through study completion, between 24 weeks and 52 weeks). Medical events that occurred between signing of the Informed Consent and the first intake of trial medication were documented as medical and surgical history section and concomitant diseases.
All adverse events and serious adverse events were recorded in the patient's file and in the Case Report Form. Adverse Events were defined as any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: NSAIDs With Possible Step-up to Golimumab | NSAIDs: All patients fulfilling the inclusion criteria will be treated according to the current recommendations for the management of axial spondyloarthritis, i.e. with 2 courses of NSAIDs. If sufficient response is acheived, the patients will continue receiving NSAIDs and after sustained remission, the therapy will be stopped. If therapy with NSAIDs provides insufficient control of disease activity, switch to therapy with Golimumab will be made. Golimumab: Patients who did not have a good treatment response to 2 NSAIDs, will be treated with golimumab sc 50mg/4 weeks. After sustained remission, the therapy will be stopped. All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (27.0) | Non-systematic Assessment | Viral or bacterial upper respiratory tract infection, including confirmed SARS-CoV-2 infections. |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Dirk Elewaut | Department of Rheumatology, Gent University Hospital | +32 9 332 22 30 | reumatologie@uzgent.be |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 19, 2021 | Jul 4, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000089183 | Axial Spondyloarthritis |
| ID | Term |
|---|---|
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
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| ID | Term |
|---|---|
| C529000 | golimumab |
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|
| At reaching primary outcome (between week 24 and week 52) |
| Ghent |
| B - Belgium |
| 9000 |
| Belgium |
| Reuma Instituut Hasselt | Hasselt | Limburg | 3500 | Belgium |
| 23139267 | 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP | ASDAS is a composite index to assess disease activity in axSpA. ASDAS parameters: 1) Total back pain 2) Patient global 3) Peripheral pain/swelling 4) Duration of morning stiffness 5) CRP in mg/L: ASDAS calculation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(max(CRP,2)+1). Parameters 1-4 are reported by patients on a visual analogue score ranging from 0 to 10. Data from five variables combine to yield a score (minimum 0.636 to no defined upper limit), higher scores indicate higher disease activity. | Mean | Standard Deviation | units on a scale |
|
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | BASDAI is a measure of disease activity which was calculated based on 6 separate questionnaire items that were answered by the patients using visual analogue scale scales with range 0-10. A weighted average was performed, where items 5 and 6 had a weight of 0.5 whereas items 1, 2, 3 and 4 had a weight of 1. Range is from 0 to 10, with 10 indicating more severe disease activity. | Mean | Standard Deviation | units on a scale |
|
| Bath Ankylosing Spondylitis Functional index (BASFI) | BASFI is a measure of physical function which was calculated based on 10 separate questionnaire items that were answered by the patients using visual analogue scales with range 0-10, an average across 10 items was calculated. The range is 0-10 with 10 indicating that the level of physical functioning is more severely affected. | Mean | Standard Deviation | units on a scale |
|
| Positive for HLA-B27 (%) | Count of Participants | Participants |
|
| Body mass index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Time from diagnosis | Time from the first diagnosis of axial spondyloarthritis to enrollment in the trial | Median | Standard Deviation | days |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Inflammatory Back Pain | IBP according to experts: four out of five of the following parameters present: (1) age at onset less than 40 years, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, (5) pain at night (with improvement upon getting up). (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Arthritis | Documented past or present active synovitis diagnosed by a doctor. | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Good response to NSAIDs | Patient-reported effect of treatment with over-the-counter administered NSAIDs taken against axial spondyloarthritis symptoms. | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Heel enthesitis | Heel enthesitis: past or present spontaneous pain or tenderness at examination at the site of the insertion of the Achilles tendon or plantar fascia at the calcaneus. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Psoriasis | Documented past or present psoriatic skin or nail lesions diagnosed by a doctor. | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Uveitis | Documented past or present anterior uveitis, diagnosed by an ophthalmologist. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Dactylitis | Documented past or present dactylitis diagnosed by a doctor. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Inflammatory bowel disease | Documented past or present inflammatory bowel disease diagnosed by a doctor. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society criteria: Elevated C-reactive protein | Measured within 3 months priort to study inclusoon or at baseline and temporally associated with patient's complaints emergence of CRP above upper normal limit in the presence of back pain, after exclusion of other causes for elevated CRP concentration. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| Assessment of SpondyloArthritis international Society criteria: Family history of spondyloarthritis | Patient reported presence in first-degree or second-degree relatives of any of the following: (a) ankylosing spondylitis, (b) psoriasis, (c) uveitis, (d) reactive arthritis, (e) inflammatory bowel disease. (Reference: Ann Rheum Dis 2009;68:777-83) | Count of Participants | Participants |
|
| CRP (mg/mL) | Mean | Standard Deviation | mg/mL |
|
|
|
| Secondary | The Proportion of Patients With Healed Lesions of the Intestinal Mucosa | According to the protocol, every patient underwent ileocolonoscopy at baseline to screen for macroscopic and microscopic (histopathologic analysis of endoscopic biopsies) signs of inflammation. If baseline ileocolonoscopy was protocolled as positive, the patient would undergo a second ileocolonoscopic assessment at the timepoint of reaching sustained clinical remission (study endpoint). The outcome measure is the proportion of patients with a negative second ileocolonoscopy. | At baseline ileocolonoscopy, macroscopic lesions justifying a repeated ileocolonoscopy at a later timepoint were found in only 1 patient. For this patient, pathologic findings present at baseline assessment were also found during the second assessment. | Posted | Count of Participants | Participants | At reaching primary outcome (between week 24 and week 52) |
|
|
|
| 0 |
| 58 |
| 0 |
| 58 |
| 19 |
| 58 |
|
| Gastroenteritis | Infections and infestations | MedDRA (27.0) | Non-systematic Assessment | Gastroenteritis |
|
| Otitis | Infections and infestations | MedDRA (27.0) | Non-systematic Assessment | External (otitis externa) or middle (otitis media) ear infection |
|
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| D001847 |
| Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D000844 | Ankylosis |
| D007592 | Joint Diseases |
| D001168 | Arthritis |