Conditions: Axial Spondyloarthritis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 64
Healthy volunteers: no

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.

Detailed description:

Arms:
arm 1: None

Interventions: intervention 1: Golimumab
Intervention descriptions: intervention 1: 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.

Protocol document:
Prot_SAP_000.pdf: 
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Protocol Go Gut trial 
version 5.0 
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Study Protocol and Statistical Analysis Plan 
 
 
 
Efficacy of golimumab in early axial spondyloarthritis 
(axSpA) in relation to gut inflammation, an early 
remission induction study (GO GUT). 
NCT03270501 
version 5.0 - 19 January 2021 


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Protocol Go Gut trial 
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PART 1: TRIAL-RELATED PART OF THE PROTOCOL       
 
1. Title of the trial 
Efficacy of golimumab in early axial spondyloarthritis (axSpA) in relation to gut inflammation, an early 
remission induction study (GO GUT).  
 
2. Trial number 
Protocol: AGO/2017/004 
EudraCT number: 2017-001728-23 
 
3. Objectives and hypothesis 
3.1 Primary objectives 
1. To describe and confirm the relationship between subclinical gut inflammation and axSpA.  
2. To evaluate whether there is a higher need of anti-tumor necrosis factor α (anti-TNFα) treatment 
in axSpA patients with (subclinical) gut inflammation compared to those without. 
 
3.2 Secondary objectives 
1. To describe the clinical response of a treat-to-target principle in early axSpA and explore the 
possibility of drug-free remission.   
2. To evaluate the relation between the presence of (subclinical) gut inflammation and the 
therapeutic response to anti-TNFα in patients with axSpA.  
3. To evaluate the relationship between (subclinical) gut inflammation on the one hand and 
remission induction and relapse on the other hand in patients with axSpA.   
 
3.3 Hypothesis 
The hypothesis of the study is that the presence of (subclinical) gut inflammation at baseline in 
patients with early active axSpA predisposes to a more severe disease defined as more need to use 
anti-TNFα therapy and a shorter time to relapse after stopping anti-TNFα therapy after obtaining 
sustained clinical remission. Overall, we hypothesize that subclinical gut inflammation is an 
important predictor in therapy response and outcome. These data could provide us better insights 
into the complex interactions between gut and joint inflammation and guide us in the therapeutic 
approach. 
 
3.4 Primary endpoint and timepoint of the endpoint. 
Clinical remission, evaluated on 2 consecutive follow-up visits (interval: 12 weeks).  


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3.5 Secondary endpoint and timepoint of the endpoint.  
Mucosal healing, evaluated by ileocolonoscopy at time of clinical remission. 
 
4. General information 
4.1 Investigators 
Ghent University Hospital (Center 01): 
Dr. Manouk de Hooge, Department of Rheumatology, Ghent University Hospital. 
 Dr. Ann-Sophie De Craemer, Department of Rheumatology, Ghent University Hospital. 
Dr. Liselotte Deroo, Department of Rheumatology, Ghent University Hospital. 
Dr. Zuzanna Lukasik, Department of Rheumatology, Ghent University Hospital. 
Prof. dr. Martine De Vos, Department of Gastroenterology, Ghent University Hospital. 
Dr. Triana Lobaton Ortega, Department of Gastroenterology, Ghent University Hospital. 
Prof. dr. Lennart Jans, Department of Radiology, Ghent University Hospital. 
Dr. Philippe Carron, Department of Rheumatology, Ghent University Hospital. 
Prof. dr. Dirk Elewaut, Department of Rheumatology, Ghent University Hospital. 
Prof. dr. Filip Van den Bosch, Department of Rheumatology, Ghent University Hospital.  
Reuma Institute Hasselt (Center 02 – clinical part of the study): 
Dr. Jan Lenaerts, Reuma Institute, Hasselt. 
Dr. Christine Langenaken, Reuma Institute, Hasselt. 
Dr. Isabelle de Wergifosse, Reuma Institute, Hasselt. 
Dr. Femke Meynen, Reuma Institute, Hasselt. 
Jessa Ziekenhuis Hasselt (Center 02 – Radiology and Gastroenterology service): 
Dr. Geert Souverijns, Department of Radiology, Jessa Ziekenhuis, Hasselt. 
Dr. Jean-Louis Coenegrachts, Department of Gastroenterology, Jessa Ziekenhuis, Hasselt. 
Imelda hospital Bonheiden (Center 03) 
Dr. Stijn Michiels, Department of Rheumatology 
Dr. Kathleen Declerck, Department of Rheumatology 
Dr. Els Van Essche, Department of Rheumatology 
Dr. Peter Bossuyt, Department of Gastroenterology 
Dr. Lieven Pouillon, Department of Gastroenterology 
Dr. Yoeri Vankan, Department of Radioloy 
Principal investigators:  
Prof. dr. Dirk Elewaut and Prof. dr. Filip Van den Bosch 
Department of Rheumatology, Ghent University Hospital 
Dirk.Elewaut@ugent.be, Filip.Vandenbosch@ugent.be 
09/332 50 74 


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4.2 Sponsor  
Ghent University. 
 
4.3 Funding 
Research grant by Merck Sharp & Dohme (MSD). 
Golimumab will be provided by MSD.  
 
4.4 Departments  
Department of Rheumatology, Ghent University Hospital.  
Department of Gastroenterology, Ghent University Hospital. 
Department of Radiology, Ghent University Hospital. 
Reuma Institute, Hasselt 
Department of Radiology, Jessa Ziekenhuis, Hasselt 
Department of Gastroenterology, Jessa Ziekenhuis, Hasselt 
Department of Rheumatology, Imelda hospital Bonheiden.  
Department of Gastroenterology, Imelda hospital Bonheiden. 
Department of Radiology, Imelda hospital Bonheiden. 
 
 
5. Introduction 
Spondyloarthritis (SpA) is an immune-mediated, inflammatory rheumatic disease concept, consisting 
of a group different diseases, sharing common genetic, clinical and radiological characteristics. 
Patients develop inflammatory back pain and/or pauci-articular peripheral arthritis/enthesitis. In the 
long term, chronic inflammation of the axial skeleton can cause osteoproliferation and ankylosis of 
sacroiliac joint and spine.  
An important feature of SpA is the frequent association with extra-articular symptoms such as 
anterior uveitis, psoriasis and inflammatory bowel disease (IBD), especially Crohn’s disease (CD) and 
to a lesser extent ulcerative colitis [1]. About 50% of SpA patients have microscopic signs of bowel 
inflammation, without gastrointestinal symptoms. These microscopic lesions can be indistinguishable 
from lesions seen in early CD, suggesting that these might represent a subclinical form of the disease. 
Even more, IBD and SpA might be two ends of the same disease spectrum. This hypothesis is further 
strengthened by the identification of common genetic susceptibility factors linking SpA and IBD 
pathogenesis [2-4]. Hence, gut involvement seems to be important for SpA pathogenesis. A clear 
clinical relationship between gut and joint inflammation with remission of the latter being associated 
with disappearance of the first and vice versa is showed in the past [5-7]. Interestingly, patients with 
chronic gut inflammation showed a higher risk of evolving to ankylosing spondylitis (AS) and were 
more likely to start anti-TNFα therapy. Furthermore, they seem to respond better to the treatment 
with biologicals. This underlines the potential clinical implications of microscopic gut inflammation in 
SpA and suggests that gut inflammation predisposes to a more extensive, persistent disease 
[unpublished data; 7,8]. In addition, results from the Ghent Inflammatory Arthritis and spondylitis 
(GIANT) cohort showed that chronic gut inflammation is linked to more extensive bone marrow 


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edema of the sacroiliac joints on magnetic resonance imaging (MRI) [9]. It has also been suggested 
that inducing mucosal healing is an important factor for long-term remission [10].  
In 2017 the Assessment of Spondyloarthritis international Society (ASAS) and the European League 
Against Rheumatism (EULAR) published an update of the axSpA treatment guidelines.  In this update 
ASAS and EULAR stress on the importance of installing a treat-to-target principle. However, they do 
not suggest a preferred target, but leave the decision to the clinician and his patient. All patients 
should be treated with 2 different non-steroidal anti-inflammatory drugs (NSAIDs) during 4 weeks in 
total, before switching to an anti-TNFα agent. This period is significantly shorter than the previous 
recommendation of 3 months treatment with NSAIDs [11].  
Golimumab is a fully human monoclonal antibody that binds and inhibits TNFα [12,13]. In Europe it is 
used, among others, in AS and non-radiographic axSpA who do not respond to NSAIDs. The 
effectiveness of golimumab is also shown in IBD [14]. Two randomized clinical trials (RCTs) have 
examined the therapeutic effects of golimumab in patients with SpA: the GO-RAISE and GO-AHEAD 
trial. Both trials showed a better ASAS 20 response at week 14 and 16, respectively, in the 
golimumab group compared to placebo. Clinical improvement was already seen 4 weeks after first 
subcutaneous administration of the medication. The treatment response was higher in patients with 
overt signs of inflammation, i.e. sacroiliitis on MRI and/or higher C-reactive protein (CRP) levels, than 
in patients without detectable inflammation. Thus, objective signs of inflammation could be a good 
predictor of treatment response. In terms of effect on imaging it showed that both sacroiliac joint 
and spine inflammation is reduced when treated with golimumab [15,16]. The safety profile of 
golimumab is comparable with that of other TNFα-inhibitors and is generally well-tolerated by 
patients.  
 
 
 
 
6. The present study 
6.1 Participants 
6.1.1 Number of participants 
The total number of patients needed is estimated to be 147 (cfr. infra: 10.1 Calculation of the sample 
size). The subjects will be recruited through the department Rheumatology of the Ghent University 
Hospital, at the Reuma Institute in Hasselt, and at the Imelda hospital in Bonheiden.  
 
6.1.2 Inclusion criteria 
In this trial we will include 147 subjects for which all of the following criteria must be met: 
- 
Subject must have a diagnosis of axSpA and classified according to ASAS criteria. 
- 
Subject is between 18 and 46 years at the screening visit. 
- 
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). 
 


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6.1.3 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. 
 
 
6.1.4 Replacement of participants 
 
Screen failures will be replaced by individuals that meet the inclusion criteria in order to reach the 
proposed target population of 147 patients. 
Drop-outs will not be replaced.  
 
6.1.5 Limitations for the participants 
There are no specific limitations for the participants other than the ones listed at section 6.1.3 
Exclusion criteria, with the exception that there is an obligation for female subjects to use 
contraceptives.  


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6.1.6 Advantages and disadvantages for the participants  
In Belgium anti-TNFα treatment for axSpA is only reimbursed for patients with sacroiliitis on MRI 
according to ASAS and an elevated CRP. In this trial the European guidelines are used, so participants 
qualify for treatment with anti-TNFα if they have sacroiliitis on MRI (according to ASAS definition) or 
an elevated CRP (they do not have to meet both criteria) [11]. Up until now Golimumab is not 
reimbursed in Belgium for the treatment of axSpA. Thus, this means an advantage for the 
participants.  
As all the investigations and treatments in this trial are considered routine clinical care, there are no 
specific disadvantages for the participants.  
 
 
General risks concerning the procedures included in the study protocol: 
- 
Risk of blood sampling: hematoma at the puncture site, residual bleeding at the puncture 
site. Some patients may feel dizzy or faint during blood sampling. The qualified nurse who 
performs the blood sampling will act professionally in order to minimize these risks. 
- 
Risk of ileocolonoscopy: this examination is generally safe. There is minimal risk of 
perforation of the intestinal mucosa. 
- 
Risk of NMR: some patients may feel anxious because subjects are asked to lay flat in a small 
tunnel (claustrophobia). No risk for allergic reactions since no contrast agents are being used. 
   
6.2 Study design and procedures  
Cfr. infra: 6.3 Flowchart. 
 
6.2.1 Screening visit 
At the screening visit the informed consent form (ICF) will be signed and inclusion/exclusion criteria 
will be checked. Subsequently routine blood tests (complete blood count, electrolytes, liver function, 
kidney function, CRP and Erythrocyte Sedimentation Rate - ESR) and additional study samples for 
inflammatory and genetic markers will be taken (4x5mL serum and 3x4mL EDTA). These additional 
samples will be stocked pseudonymized in a prospective research biobank (“Biobank van menselijk 
lichaamsmateriaal van patiënten met reumatische en/of musculoskeletale aandoeningen en gezonde 
controles”, EC 2019/0314, medical administrator: prof. dr. Dirk Elewaut). Also, HIV and hepatitis 
serology will be checked as part of the routine blood analyses and a Mantoux tuberculin skin test and 
a chest X-ray will be executed to exclude latent tuberculosis.   
 
6.2.2 Baseline and follow-up 
All subjects will undergo a baseline (pre-treatment) ileocolonoscopy to detect whether there is 
(subclinical) gut inflammation; this procedure is part of standard of care. Subjects must prepare for 
the ileocolonoscopy by avoiding consumption of high-fiber food or food rich in kernels from 3 days in 
advance. 
Further preparation procedure for UZ Gent and the Reuma Institute Hasselt: 


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The day before the ileocolonoscopy, only liquid food is allowed. The evening before the examination, 
the subject needs to drink 1 portion of Plenvu in 500cc water and an extra 500cc of clear water. This 
needs to be repeated on the morning of the examination.  
Further preparation procedure for Imelda hospital Bonheiden: 
The day before the ileocolonoscopy at 12h a light meal is allowed, no fruit, no vegetables and no 
brown bread is allowed. Afterwards no food is allowed anymore, only drinking is allowed. And at 18h 
the subject needs to drink 2 portions of colofort in 2 liters water over 2 hours. On the morning at 7h 
the subject again needs to drink 2 portions of colofort in 2 liters water over 2 hours. 
 
These preparations ensure an adequate cleaning of the intestines in order to optimize the 
endoscopists’ view.  
During the ileocolonoscopy, for all sites routine biopsies for pathological examination (4 biopsies in 
ileum, 8 biopsies in colon) and extra biopsies for RNA sequencing (2 biopsies in ileum, 2 biopsies in 
colon) will be taken. Additional for functional analyses, site specific (only in Ghent University 
Hospital), also 6 biopsies in ileum and 6 biopsies in colon will be taken. The investigators and the 
patient will be blinded for the results of this ileocolonoscopy until the subject is switched to 
golimumab. Only in case of major abnormalities necessitating medical intervention, the investigator 
will be made aware of the results of the ileocolonoscopy earlier. The central reader will make sure 
that 50% of the included patients will have subclinical gut inflammation and 50% of the patients will 
not have any subclinical gut inflammation. Additional blood samples will be drawn for functional 
analyses (site specific: only sampling of 4x10mL heparin blood in Ghent University Hospital) and 1 
stool sample will be collected and stored pseudonymized in the prospective research biobank. After 
the trial has ended, all stool samples will be subject to biochemical and microbiome analyses (in one 
batch), performed by the laboratory attached to the department of Rheumatology of Ghent 
University Hospital.  
 
At baseline, a treat-to-target principle will be installed. All subjects will receive a full anti-
inflammatory dose NSAID for 2 weeks according to the routine clinical practice.  
Visits are scheduled on week 0, 2, 4, 16, 28, 40 and 52 (± 2 weeks). If subjects have a clinically 
important improvement, defined as an ASDAS score < 1.3 or a decrease of at least 1.1 in ASDAS score 
resulting in a maximum of 2.1, subjects will continue with the same treatment. If subjects do not 
meet this disease activity state after a treatment with the first NSAID, a different NSAID will be 
installed at full anti-inflammatory dose during 2 weeks. Again, if subjects have a clinically important 
improvement (compared to the baseline situation before initiating the first NSAID therapy) after 2 
weeks treatment with the second NSAID, subjects continue with this treatment. If this disease 
activity state is not reached at week 4, the NSAID treatment will be stopped and subjects will start 
treatment with golimumab (anti-TNFα therapy, 50mg every 4 weeks, subcutaneous injection) in 
monotherapy. At every trial visit routine blood tests (inflammatory markers at week 0, 2, 4 and a 
complete blood count, electrolytes, liver function, kidney function, inflammatory markers at 
screening, week 16, 28, 40 and 52) will be performed. Additional study samples for inflammatory 
markers (2x5mL serum) will be taken at every trial visit (except for the baseline visit at week 0, no 
additional serum samples) and stored in the prospective research biobank. After 4 weeks NSAID 
treatment, after 6 months golimumab treatment and at time of relapse stool samples (1 sample at 
each time point) and additional blood samples (site specific: only sampling of 3x10mL heparin blood 
in Ghent University Hospital) will be collected. The additional heparin blood samples are used 
immediately for functional analysis; the stool samples are stored pseudonymized in the prospective 
research biobank. After the trial has ended, all stool samples will be subject to biochemical and 
microbiome analyses (in one batch), performed by the laboratory attached to the department of 
Rheumatology of Ghent University Hospital.   


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Maximal study duration for a subject is 12 months.  
 
6.2.3 Start of anti-TNFα 
If a subject starts on anti-TNFα treatment, the timing of the study visits will be recalculated: part B 
+12 weeks, +24, +36, etc.  
 
6.2.4 Remission 
If subjects are in remission (ASDAS < 1.3) during the follow-up period on 2 consecutive study visits 
(with an interval of 12 weeks), subjects are considered to be in sustained clinical remission and 
golimumab or NSAID therapy will be stopped and a second ileocolonoscopy will be performed in 
those patients from whom the first colonoscopy showed (subclinical) gut inflammation. During the 
ileocolonoscopy, for all sites routine biopsies for pathological examination (4 biopsies in ileum, 8 
biopsies in colon) and extra biopsies for RNA sequencing (2 biopsies in ileum, 2 biopsies in colon) will 
be taken. Additional for functional analyses, site specific (only in Ghent University Hospital), also 6 
biopsies in ileum and 6 biopsies in colon will be taken. Additional blood samples (3x10mL heparin) 
will be taken prior to the ileocolonoscopy for simultaneous functional analysis (site specific: only 
sampling of heparin blood in Ghent University Hospital). A new MRI of the sacroiliac joints will be 
performed in all patients in which treatment was withdrawn because of sustained clinical remission 
on 2 consecutive clinical visits. For all those patients the study ends and follow-up and treatment will 
be foreseen every 6 months in our local Be-Giant register according to the routine clinical practice.  
 
 
6.2.5 Relapse 
- Relapse is defined as: 
• 
∆ ASDAS ≥ 0,6 (compared to ASDAS at time of sustained clinical remission) and ASDAS ≥ 1,3 
(17) 
AND 
• 
PASS (= patient acceptable symptom state) for the upcoming 6 months is NO (meaning: 
would the patient be satisfied if current clinical situation would continue for the next 6 
months) 
AND 
• 
Expert opinion: the assessing physician believes that ∆ ASDAS reported by the patient is most 
probably related to a relapse of spondyloarthritis. If not, an alternative hypothesis/probable 
diagnosis must be provided. 
  
- In case of relapse, the time point will be registered in the study, extra blood samples will be drawn 
(2x5mL serum; site specific: 3x10mL heparin blood only in Ghent University Hospital) and the 


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subjects will be treated according to the routine clinical practice. In reality, this will most likely match 
the last remission-inducing treatment of the subject.  
 
 
6.2.6 No remission achieved 
When the subject is still not in sustained remission after 48 weeks of golimumab treatment, defined 
as ASDAS < 1.3 on 2 consecutive study visits, the patient will stop participating in this study and will 
be followed in the routine clinical practice.  
 
 
6.2.7 Procedures 
6.2.7.1 Screening visit 
- 
ICF 
- 
Check fulfillment of the inclusion and exclusion criteria 
- 
Anamnesis 
- 
Medical and family history 
- 
Demographic data 
- 
Symptom duration 
- 
Current and past medication (NSAID): dosage and duration 
- 
Clinical examination: 
o  weight, length, vital symptoms (blood pressure, heart frequency) 
o BASMI 
o Total tender and swollen joint count (TJC/SJC) (78) 
o Dactylitis assessment 
o MASES + plantar fascia + quadriceps and patellar tendon 
- 
Assessment of work participation (site-specific: only in Ghent University Hospital). 
- 
Questionnaires: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing 
Spondylitis Functional Index (BASFI), Patient global assessment of disease activity, patient 
global pain assessment. Site-specific (only in Ghent University Hospital): Work Productivity 
and Activity Impairment (WPAI), health care consumption, EQ5D.  
- 
Laboratory investigation (incl. 4x5mL serum + 3x4mL EDTA for additional research) 
- 
Imaging: MRI SI joints (if not already done), chest X-ray 
- 
Mantoux tuberculin test 
- 
Pregnancy test for female subjects (on blood sample) 
 
6.2.7.2 Baseline 
 
- 
Laboratory investigation (site-specific: only in Ghent University Hospital 4x10mL heparin 
blood for additional research) 
- 
Stool sample  
- 
Ileocolonoscopy including for all sites routine biopsies for pathological examination (4 
biopsies in ileum, 8 biopsies in colon) and extra biopsies for RNA sequencing (2 biopsies in 
ileum, 2 biopsies in colon) will be taken. Additional for functional analyses, site specific (only 
in Ghent University Hospital), also 6 biopsies in ileum and 6 biopsies in colon will be taken. 
- 
Start treat-to-target approach 


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- 
AND if baseline visit is performed more than 4 weeks after the screening visit: 
o Anamnesis 
o Current and past medication (NSAID): dosage and duration 
o Clinical examination: 
▪ 
 weight, length, vital symptoms (blood pressure, heart frequency) 
▪ 
BASMI 
▪ 
Total tender and swollen joint count (TJC/SJC) (78) 
▪ 
Dactylitis assessment 
▪ 
MASES + plantar fascia + quadriceps and patellar tendon 
o Questionnaires: cfr. 6.2.7.1 (excl. WPAI, health care consumption and EQ5D 
 
6.2.7.3 Follow-up visits 
 
- 
Anamnesis 
- 
Current and past medication: dosage and duration 
- 
Clinical examination: 
o  weight, length, vital symptoms (blood pressure, heart frequency) 
o BASMI 
o Total tender and swollen joint count (TJC/SJC) (78) 
o Dactylitis assessment 
o MASES + plantar fascia + quadriceps and patellar tendon 
- 
Questionnaires: cfr. 6.2.7.1 (WPAI, health care consumption and EQ5D are site-specific (only 
in Ghent University Hospital) and only at time of switch from NSAID to anti-TNF and at time 
of sustained remission). 
- 
Assessment of work participation (site-specific: only in Ghent University Hospital) only at 
time of switch from NSAID to anti-TNF and at time of sustained remission. 
- 
Laboratory investigation (incl. 2x5mL serum at every follow-up visit for additional research; 
site-specific: only at Ghent University Hospital 3x10mL heparin after 4 weeks of NSAIDs, 6 
months of golimumab, at time of sustained clinical remission (if and on the same day as the 
second ileocolonoscopy incl. biopsies cfr. 6.2.7.2) and at time of relapse)) 
- 
Stool sample (after 4 weeks NSAID, 6 months golimumab and at time of relapse) 
 
 
 


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6.3 Flowchart 
 
Screening period:  
 
 
  
Baseline/week 0: 
 
 
 
 
Week 2:  
 
 
 
 
 
Week 4: 
 
 
 
 
 
Week 16: 
 
 
 
 
 
 
 
 
- Check inclusion and exclusion criteria 
- Blood samples 
- Chest X-ray and Mantoux test 
- Pregnancy test (for women) 
- MRI SI joints (if not already done) 
- 
Stool sample 
- 
Perform ileocolonoscopy 
- 
Start first NSAID treatment 
Start second NSAID treatment 
Continue with first NSAID 
treatment  
Patient has no clinically 
important improvement. 
Patient has clinically important 
improvement  
Start golimumab 50mg SC 
monthly in monotherapy if on 
second NSAID; start second 
NSAID if on first NSAID 
Continue with NSAID 
treatment  
Patient has no clinically 
important 
improvement 
Patient has clinically important 
improvement 
Calculation of the ASDAS to determine 
whether patient is in remission 
Relapse  
No relapse 
Relapse  
No relapse 


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Week 28: 
 
 
 
 
 
Week 40: 
 
 
 
 
 
Week 52: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Calculation of the ASDAS to determine 
whether patient is in remission 
Calculation of the ASDAS to determine 
whether patient is in remission 
Patient is not in remission on 2 
consecutive visits 
Stop study, perform 
second colonoscopy 
(if the first one was 
positive) and second 
MRI and follow-up 
in routine clinical 
practice, report 
time to relapse. 
Calculation of the ASDAS to determine 
whether patient is in remission 
Patient is not in remission on 2 
consecutive visits 
Patient is in remission on 2 consecutive 
visits 
Patient is not in remission on 2 
consecutive visits 
Stop study and 
follow-up in routine
clinical practice. 


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6.4 Study table 
† Site-specific: only in Ghent University Hospital (Center 01); * MRI SIG at screening if not already done in the context of diagnosis; ° Ileocolonoscopy including for all sites biopsies for 
pathological examination (4 in ileum, 8 in colon) and RNA sequencing (2 in ileum, 2 in colon). Additional for functional analyses (site specific: only in Ghent University Hospital: 6 in ileum, 6 in 
colon). 
 
Clinical  
examination 
(incl. BASMI) 
Patient 
questionnaires 
Blood: 
4x5mL 
serum + 
3x4mL 
EDTA 
Blood: 
2x5mL 
serum 
Blood: 
4x10mL 
heparin † 
Pregnancy 
test (for 
female 
subjects) 
Screening 
tuberculosis: 
chest X-ray 
and Mantoux 
Stool sample 
Ileocolon
oscopy° 
ASDAS MRI SIG 
Medication 
(golimumab) 
(starts after 
treatment 
failure on 
NSAIDs) 
Screening 
X 
X 
X 
 
 
X 
X 
 
 
X 
X * 
 
Baseline 
X 
X 
 
 
X 
 
 
X 
X 
X 
 
 
Follow-up 
visits  
X 
X 
 
X 
 
 
 
 
 
X 
 
X (every 4 
weeks) 
Extra after 
4 weeks 
NSAIDs 
 
 
 
 
X  
(only 3 
tubes) 
 
 
X 
 
 
 
 
Extra after 
6 months 
anti-TNF 
 
 
 
 
X 
(only 3 
tubes) 
 
 
X 
 
 
 
 
Extra at 
remission 
 
 
 
 
X 
(only 3 
tubes, if 
and on 
same day 
as colono-
scopy) 
 
 
 
If first 
ileocolono
scopy was 
positive 
 
X 
 
Extra at 
relapse 
X 
X 
 
X 
X 
(only 3 
tubes) 
 
 
X 
 
X 
 
 


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6.5 Medication 
- 
NSAID therapy will be given orally in full anti-inflammatory dose according to the routine 
clinical practice. 
- 
Golimumab, provided by MSD, will be given subcutaneous at the dose of 50 mg every 4 
weeks. 
 
6.5.1 Composition and dosing 
 
Golimumab is a human monoclonal antibody (mab) with an IgG1 heavy chain isotype and a kappa 
light chain isotype that binds TNFα with high affinity and specificity. The molecule is produced by a 
stable, recombinant murine cell line transfected with DNA coding for the heavy and light chains of 
the mab. Golimumab is supplied as a liquid in a prefilled syringe (PFS) for subcutaneous 
administration. Each prefilled syringe contains 50mg (0.5mL fill of liquid) golimumab, histidine, 
sorbitol and polysorbate 80 at pH 5.5. No preservatives are present. The prefilled syringe with 
golimumab will be administrated subcutaneously every 4 weeks. This is the same dose/regimen used 
as in the previously performed Phase III golimumab studies. 
 
6.5.2 Producer 
Golimumab (Simponi): Janssen Biologics B.V. 
6.5.3 Distributor 
Golimumab: Janssen Biologics B.V. 
6.5.4 Packaging 
Golimumab will be supplied as a sterile liquid in a 0.5mL single-use prefilled syringe for subcutaneous 
administration. 
6.5.5 Administration way 
Golimumab will be administrated subcutaneously every 4 weeks. 
6.5.6 Labelling 
The following particulars will be added to the original packaging, but will not obscure the original 
labelling: 
 
I) Studie/Etude Go-Gut EUDRACT nr: 2017-001728-23 
II) Naam/nom SPONSOR: Prof. dr. Dirk Elewaut – UGent 
III) Naam/nom Dr.: 
IV) Centrum/centre:  
V) Patient Nr./N° patient: 
VI) Bezoek Nr./N° de visite: 
Alleen voor klinisch onderzoek/Uniquement récherche biomédicale 
 
6.5.7 Storage conditions 
Golimumab will be stored in a locked refrigerator, which will be temperature-controlled by using a 
continuous temperature logger (2 °C to 8 °C) in original carton until time of use. It will be protected 
from light. It will be not frozen or shaken. 
6.5.8 Known side effects of the medication 
For the known side effects of golimumab we refer to those described in the latest update of the 
SmPC available on the EMA website. 


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Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in the 
controlled Phase III rheumatoid arthritis (RA), psoriatic arthritis (PsA), and AS studies through week 
16, occurring in 7.2% of golimumab treated patients as compared with 5.8% of control patients. The 
most serious ADRs that have been reported for Simponi include serious infections (including sepsis, 
pneumonia, TB, invasive fungal and opportunistic infections), demyelinating disorders, lymphoma, 
HBV reactivation, CHF, autoimmune processes (lupus-like syndrome) and haematologic reactions. 
ADRs observed in clinical studies and reported from world-wide post-marketing use of golimumab 
are listed in Table 1. Within the designated system organ classes, the adverse drug reactions are 
listed under headings of frequency and using the following convention: Very common (≥ 1/10); 
Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very 
rare (< 1/10,000); Not known (cannot be estimated from the available data). 
 
Table 1 
Tabulated list of ADRs 
 
Infections and infestations 
Very common: Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis and rhinitis) 
Common: Bacterial infections (such as cellulitis), viral infections (such as influenza and herpes), 
bronchitis, sinusitis, superficial fungal infections 
Uncommon: Septic shock, sepsis, tuberculosis, lower respiratory tract infection (such as pneumonia), 
opportunistic infections (such as invasive fungal infections [histoplasmosis, coccidioidomycosis, 
pneumocytosis], bacterial, atypical mycobacterial infection and protozoal), pyelonephritis, abscess, 
bacterial arthritis, infective bursitis 
Rare: Hepatitis B reactivation 
 
Neoplasms, benign, malignant and unspecified 
Uncommon: Neoplasms (such as skin cancer, squamous cell carcinoma and melanocytic naevus) 
Rare:  Lymphoma, leukaemia, melanoma 
Not known: Merckel cell carcinoma *  
 
Blood and lymphatic system disorders 
Common: Anaemia 
Uncommon: Leucopaenia, thrombocytopenia 
Rare: Pancytopaenia 
Not known: Aplastic anaemia * 
 


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Immune system disorders 
Common: Allergic reactions (bronchospasm, hypersensitivity, urticaria), autoantibody positive 
Rare: Serious systemic hypersensitivity reactions (including anaphylactic reaction) , vasculitis 
(systemic), sarcoidosis 
 
Endocrine disorders 
Uncommon: Thyroid disorder (such as hypothyroidism, hyperthyroidism and goitre) 
 
Metabolism and nutrition disorders 
Uncommon: Blood glucose increased, lipids increased 
 
Psychiatric disorders 
Common: Depression, insomnia 
 
Nervous system disorders 
Common: Dizziness, paraesthesia, headache 
Uncommon: Demyelinating disorders (central and peripheral), balance disorders, dysguesia 
 
Eye disorders 
Uncommon: Visual disorders (such as blurred vision and decreased visual acuity), conjunctivitis, eye 
allergy (such as pruritis and irritation) 
 
 
 
Cardiac disorders 
Uncommon: Congestive heart failure (new onset or worsening), arrhythmia, ischemic coronary artery 
disorders  
 
Vascular disorders 
Common: Hypertension 
Uncommon: Thrombosis (such as deep venous and aortic), Raynaud’s phenomenon, flushing 
 


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Respiratory, thoracic and mediastinal disorders 
Uncommon: Asthma and related symptoms (such as wheezing and bronchial hyperactivity) 
Rare: Interstitial lung disease 
 
Gastrointestinal disorders 
Common: Constipation, dyspepsia, gastrointestinal and abdominal pain, nausea 
Uncommon: Gastrointestinal inflammatory disorders (such as gastritis and colitis), gastro-
oesophageal reflux disease, stomatitis 
 
Hepatobiliary disorders 
Common: Alanine aminotransferase increased, aspartate aminotransferase increased 
Uncommon: Cholelithiasis, hepatic disorders 
 
Skin and subcutaneous tissue disorders 
Common: Alopecia, dermatitis, pruritus, rash 
Uncommon: Psoriasis (new onset or worsening of pre-existing psoriasis, palmar/plantar and 
pustular), urticaria, vasculitis (cutaneous) 
Rare: skin exfoliation 
 
Musculoskeletal and connective tissue disorders 
Rare: Lupus-like syndrome 
 
Renal and urinary disorders 
Uncommon: Bladder disorders 
Rare: Renal disorders 
 
Reproductive system and breast disorders 
Uncommon: Breast disorders, menstrual disorders 
 
General disorders and administration site conditions 
Common: Pyrexia, asthenia, injection site reaction (such as injection site erythema, urticaria, 
induration, pain, bruising, pruritus, irritation and paraesthesia), impaired healing, chest discomfort 


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Injury, poisoning and procedural complications 
Uncommon: Bone fractures 
*: Observed with other TNF-blocking agents, but not observed in clinical studies with golimumab. 
 
6.5.9 Fertility, pregnancy and lactation 
Data on fertility, pregnancy and lactation is described in the latest update of the SmPC available on 
the EMA website. 
Pregnancy 
There are no adequate data on the use of golimumab in pregnant women. Due to its inhibition of 
TNF, golimumab administered during pregnancy could affect normal immune responses in the 
newborn. Studies in animals do not indicate direct or indirect harmful effects with respect to 
pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3 of 
SmPC). 
Golimumab crosses the placenta. The use of golimumab in pregnant women is not recommended; 
golimumab should be given to a pregnant woman only if clearly needed. Following treatment with a 
TNF-blocking monoclonal antibody during pregnancy, the antibody has been detected for up to 6 
months in the serum of the infant born by the treated woman. Consequently, these infants may be at 
increased risk of infection. Administration of live vaccines to infants exposed to golimumab in utero 
is not recommended for 6 months following the mother’s last golimumab injection during pregnancy 
(see sections 4.4 and 4.5 of SmPC). 
Breastfeeding 
It is not known whether golimumab is excreted in human milk or absorbed systemically after 
ingestion. Golimumab was shown to pass over to breast milk in monkeys, and because human 
immunoglobulins are excreted in milk, women must not breast feed during and for at least 6 months 
after golimumab treatment. 
Fertility 
No animal fertility studies have been conducted with golimumab. A fertility study in mice, using an 
analogous antibody that selectively inhibits the functional activity of mouse TNFα, showed no 
relevant effects on fertility (see section 5.3 of SmPC). 
Female participants are obliged to use contraception (oral, condom, IUD, …) during the trial and until 
6 months after the end of the trial. It’s recommended to use double contraception by both the study 
participants and his/her partner.   
 
Male participants: no risks concerning their partners’ pregnancy.   
 
6.5.10 Drug accountability 
The arrival of the study medication at the hospital pharmacy and the delivery to the study site 
(Department of Rheumatology) will be documented. 


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Drug accountability will be documented with the description of the batch number, date  of 
administration to the patient, expiration date, the amount that is administered and the route of 
administration on a separate drug accountability log in order to maintain transparency. 
 
 
6.6 Additional research 
 
We will also examine non-invasive surrogate markers for gut inflammation and therefore we will 
collect blood samples at every study visit and stool samples at baseline, after 4 weeks of NSAID 
treatment, after 6 months of golimumab treatment and at time of relapse. These are to investigate 
e.g. the serum and fecal calprotectin levels and to perform in depth immunophenotyping (flow 
cytometry) and microbiome analysis. At the screening visit we will also collect additional blood  
samples for genetic analyses (relevant single nucleotide polymorphisms for overlap SpA and IBD). All 
analyses will be performed within a context relevant to the SpA concept.  
All biological samples (blood, stool, gut biopsies and its derivatives) will be collected and stored 
pseudonymized  during 20 years in the prospective research biobank of the department of 
rheumatology of the Ghent University Hospital (“Biobank van menselijk lichaamsmateriaal van 
patiënten met reumatische en/of musculoskeletale aandoeningen en gezonde controles”, EC 
2019/0314, medical administrator: prof. dr. Dirk Elewaut). For the Imelda Hospital in Bonheiden 
(Center 03) these biological samples will first be stored on site as part of the prospective research 
biobank of the department of rheumatology of the Ghent University Hospital and shipped regularly 
(cooled transport at -80°C) in batch to the Gent University Hospital.  The only exception concerns the 
gut biopsies from patients recruited at the Reuma Institute Hasselt (Center 02): these samples will be 
collected in Jessa Hospital, will be locally registered and stored (temporarily) in the Jessa Biobank 
(medical administrator: dr. Jean-Luc Rummens – no processing required except for immediate 
freezing) and will be transferred at once (cooled transport at -80°C) to the prospective research 
biobank of the department of Rheumatology of Ghent University Hospital after the study has ended. 
All analysis on additional study samples will be performed by the laboratory attached to the 
department of Rheumatology of the Ghent University Hospital (Medical Research Building, MRB). 
Some analyses will be conducted by the Flemish institute for biotechnology (VIB – Vlaams Instituut 
voor Biotechnologie).   
 
7. Randomisation/blinding  
- Randomisation: not applicable. 
- Blinding: the investigator and his team as well as the patient will be blinded for the results of the 
ileocolonoscopy until the patient is switched to golimumab. Only in case of major abnormalities 
necessitating medical intervention, the investigator will be made aware of the results of the 
ileocolonoscopy earlier.  
 
8. Prior and concomitant medication 
The subject will be excluded if he/she had/used: 
- 
Full anti-inflammatory dose of NSAIDs for more than 4 weeks for the duration of the axSpA 
symptoms. 


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- 
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. 
 
During the trial there are no specific limitations for concomitant therapy, with exception of the use of 
DMARDS or other biologicals, while on therapy with golimumab.  
 
 
9. Reporting adverse events  
List of abbreviations 
AE: Adverse Event 
CA: Competent Authority 
EC: Ethics Committee 
SAE: Serious Adverse Event 
SSAR: Suspected Serious Adverse Reaction 
SUSAR: Suspected Unexpected Serious Adverse Reaction 
 
Adverse events (AE) 
The following information will be recorded: 
• 
nature of adverse event; 
• 
date and time of occurrence and disappearance; 
• 
intensity: mild, moderate or severe; 
• 
frequency: once, continuous or intermittent; 
• 
decision regarding study: continuation or withdrawal; 
• 
relation to the study medication (see below). 
AE’s will be recorded from the first drug administration until the end of the trial. 
Special attention will be given to those subjects who have discontinued the trial for an AE, or who 
experienced a severe or a serious AE. 
 
Definitions of Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including 


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an abnormal finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
Serious Adverse Avent (SAE) 
Any untoward medical occurrence that at any dose: 
- results in death; 
- is life-threatening; 
- requires inpatient hospitalization or prolongation of existing hospitalization; 
- results in persistent or significant disability/incapacity; 
or 
- is a congenital anomaly/birth defect. 
Note: Medical and scientific judgement should be exercised in deciding whether expedited reporting 
is appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the outcomes listed in the definition above. 
Unexpected adverse event 
An adverse event, the nature or severity of which is not consistent with the applicable product 
information (e.g., Investigator's Brochure for an unapproved investigational product or package 
insert/summary of product characteristics for an approved product). 
Life-threatening 
Any event in which the subject was at risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it were more severe. 
Associated with the use of the drug 
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable or definitive. 
 
Attribution definitions 
Not related 
An adverse event which is not related to the use of the drug. 
Unlikely 
An adverse event for which an alternative explanation is more likely - e.g. concomitant drug(s), 
concomitant disease(s), and/or the relationship in time suggests that a causal relationship is unlikely. 
Possible 
An adverse event which might be due to the use of the drug. An alternative explanation - e.g. 
concomitant drug(s), concomitant disease(s), - is inconclusive. The relationship in time is reasonable; 
therefore the causal relationship cannot be excluded. 


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Probable 
An adverse event which might be due to the use of the drug. The relationship in time is suggestive 
(e.g. confirmed by dechallenge). An alternative explanation is less likely - e.g. concomitant drug(s), 
concomitant disease(s). 
Definitely 
An adverse event which is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation - e.g. concomitant drug(s), concomitant disease(s). The relationship in 
time is very suggestive (e.g. it is confirmed by dechallenge and rechallenge). 
 
Reporting of adverse events 
Adverse events will be reported between the first dose administration of trial medication and the last 
trial related activity. 
All AEs and SAE’s will be recorded in the patient’s file and in the CRF. All SAE’s will be reported as 
described below.   
Medical events that occur between signing of the Informed Consent and the first intake of trial 
medication will be documented on the medical and surgical history section and concomitant diseases 
page of the CRF. 
SAE’s occurring within a period of 30 days following the last intake of trial medication will also be 
handled as such if spontaneously reported to the investigator. 
All serious adverse events (SAE) and pregnancies occurring during clinical trials must be reported by 
the local Principal Investigator within 24 hours after becoming aware of the SAE to: 
• 
The local EC; 
• 
HIRUZ Clinical Trial Unit (CTU) of the University Hospital Ghent; 
• 
The National Coordinating Investigator (in case of multicenter trials); 
This reporting is done by using the appropriate SAE form. For the contact details, see below. 
It is the responsibility of the local Principal Investigator to report the local SAE’s to the local EC. 
In case the National Coordinating investigator decides the SAE is a SUSAR (Suspected Unexpected 
Serious Adverse Reaction), HIRUZ CTU will report the SUSAR to the Central EC and the CA within the 
timelines as defined in national legislation. The National Coordinating Investigator reports the SUSAR 
to all local Principal Investigators and to MSD. 
In case of a life-threatening SUSAR the entire reporting process must be completed within 7 calendar 
days.  In case of a non life-threatening SUSAR the reporting process must  completed within 15 
calendar days. 
The first report of a serious adverse event may be made by telephone, e-mail or facsimile (FAX).  
Contact details of HIRUZ CTU: 
e-mail:  hiruz.ctu@uzgent.be  
tel.: 09/332 05 00 


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Protocol Go Gut trial 
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fax: 09/332 05 20 
Contact details of the Principal/National Coordinating Investigator: 
e-mail: dirk.elewaut@ugent.be, filip.vandenbosch@ugent.be  
tel.: 09/332 50 74 
fax: 09/332 47 87 
Contact details MSD: 
SAE reports and any other relevant safety information are to be forwarded by the National 
Coordinating investigator to MSD GS  
facsimile number:  +1-215-993-1220 
 
The investigator must provide the minimal information: i.e. trial number, subject's initials and date of 
birth, medication code number, period of intake, nature of the adverse event and investigator's 
attribution. 
This report of a serious adverse event by telephone must always be confirmed by a written, more 
detailed report. For this purpose the appropriate SAE form will be used. Pregnancies occurring during 
clinical trials are considered immediately reportable events. They must be reported as soon as 
possible using the same SAE form. The outcome of the pregnancy must also be reported. 
If the subjects are not under 24-hour supervision of the investigator or his/her staff (out-patients, 
volunteers), they (or their designee, if appropriate) must be provided with a "trial card" indicating 
the name of the investigational product, the trial number, the investigator's name and a 24-hour 
emergency contact number. 
 
Annual Safety Reporting 
HIRUZ CTU will ask the National Coordinating Investigator for an annual report containing an 
overview of all SSARs (Suspected Serious Adverse Reaction) and a summary regarding the safety of 
the trial subjects. HIRUZ CTU will send this report to the Central EC and the CA within the timelines as 
defined in national legislation. The National Coordinating Investigator will pass this annual report to 
all local Principal Investigators. 
 
10. Analysis of the study 
10.1 Calculation of the sample size 
This estimation is based on a pilot study evaluating Ankylosing Spondylitis Disease Activity Score 
(ASDAS) response to anti-TNFα in axSpA patients with and without gut inflammation [Cypers H, 
unpublished data]. Based on these proportions, we estimate that the sample size necessary for 
detecting a significant difference (95% confidence interval) in ASDAS category (ASDAS < 2.1 yes/no) 
after golimumab treatment between patients with versus without gut inflammation would be 55 per 
group i.e. 110 patients in the golimumab arm, for a power of 80%. 
 


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Protocol Go Gut trial 
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10.2 Analysis of the images and the samples 
Central reading will be performed by the departments Rheumatology and Radiology of the Ghent 
University Hospital ( dr. M. de Hooge and prof. dr. Lennart Jans). Radiological images of patients 
enrolled at Reuma Institute Hasselt (Center 02) and at Imelda hospital Bonheiden (center 03), will be 
pseudonymized and uploaded on an electronic device (eg. external HDD). At the end of the trial, the 
electronic device with all the pseudonymized images will be send by secured postal mail to the 
Rheumatology department of Ghent University Hospital to allow for central reading.  
The blood samples, stool samples and gut biopsies will finally all be stored in the prospective 
research biobank of the department of rheumatology of the Ghent University Hospital (“Biobank van 
menselijk lichaamsmateriaal van patiënten met reumatische en/of musculoskeletale aandoeningen 
en gezonde controles”, EC 2019/0314, medical administrator: prof. dr. Dirk Elewaut). For the Imelda 
Hospital in Bonheiden (Center 03) these biological samples will first be stored on site as part of the 
prospective research biobank of the department of rheumatology of the Ghent University Hospital 
and shipped regularly in batch to the Gent University Hospital. The gut biopsies from patients 
recruited at the Reuma Institute Hasselt (Center 02) will be collected at Jessa Hospital, will be 
registered and stored (temporarily) in the Jessa Biobank (medical administrator: dr. Jean-Luc 
Rummens – no processing required except for immediate freezing) and will be transferred at once 
(cooled transport at -80°C) to the prospective research biobank of the department of Rheumatology 
of Ghent University Hospital after the study has ended. Subsequently all samples will be analysed by 
the laboratory attached to the department of Rheumatology of the Ghent University Hospital 
(Medical Research Building, MRB) and by the VIB. These are to investigate e.g. the serum and fecal 
calprotectin levels and to perform in depth immunophenotyping (flow cytometry). Reuma Institute 
Hasselt, Jessa Ziekenhuis Hasselt nor Imelda hospital Bonheiden is expected to perform any analyses 
on any of the additionally collected study samples.  
 
10.3 Statistical analysis  
The statistical analysis will be performed by the department of Rheumatology of the Ghent 
University Hospital in collaboration with the department of Biostatistics of the Ghent University.  
 
11. Insurance 
Faultless liability Ghent University. 
 
12. Publication policy  
The results of this trial will be published in an A1-journal. The privacy of the participants will be 
respected at all times.  
 
PART 2: GENERAL PART OF THE PROTOCOL 
 


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Protocol Go Gut trial 
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13. Independent Ethics Committee (IEC) / Institutional Review Board (IRB)  
This trial can only be undertaken after full approval of the protocol and addenda has been obtained 
from the IEC/IRB. This document must be dated and clearly identify the protocol, amendments (if 
any), the informed consent form and any applicable recruiting materials and subject compensation 
programs approved. During the trial, the following documents will be sent to the IEC/IRB for their 
review:  
- 
reports of adverse events that are serious, unexpected and associated with the study 
- 
all protocol amendments and revised informed consent form (if any) 
Amendments should not be implemented without prior review and documented approval/favorable 
opinion from the IEC/IRB except when necessary to eliminate an immediate hazard to trial subjects 
or when the change involves only logistical or administrative aspects of the trial. At the end of the 
trial, the investigator will notify the IEC/IRB about the trial completion.  
 
14. ICH/GCP guidelines  
This trial will be conducted in accordance with the protocol, current ICH-GCP guidelines and 
applicable law(s). Good Clinical Practice (GCP) is an international ethical and scientific quality 
standard for designing, conducting, recording and reporting trials that involve the participation of 
human subjects. Compliance with this standard provides public assurance that the rights, safety and 
well-being of trial subjects are protected, consistent with the principles that have their origin in the 
Declaration of Helsinki, and that the clinical trial data are credible.  
 
15. Subject information and informed consent  
Prior to entry in the trial, the investigator must explain the procedure of the trial and the implication 
of participation to potential subjects or their legal representatives. Subjects will be informed that 
their participation is voluntary and that they may withdraw consent to participate at any time. 
Participating subjects will be told that competent authorities and authorized persons may access 
their records without violating the confidentiality of the subject, to the extent permitted by the 
applicable law(s) and/or regulations. By signing the Informed Consent Form (ICF), the subjects or 
legally acceptable representatives are authorizing such access. After this explanation and before 
entry to the trial, written, dated and signed informed consent should be obtained from the subject or 
legally acceptable representative. The ICF should be provided in a language sufficiently understood 
by the subject. Subjects must be given the opportunity to ask questions. The subject or legally 
acceptable representative will be given sufficient time to read the ICF and to ask additional 
questions. After this explanation and before entering the trial, consent should be appropriately 
recorded by means of either the subject's or his/her legal representative's dated signature or the 
signature of an independent witness who certifies the subject's consent in writing. After having 
obtained the consent, a copy of the ICF must be given to the subject. In case the subject or legally 
acceptable representative is unable to read, an impartial witness must attest the informed consent.  
 
16. Case Report Forms  


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The source documents are to be completed at the time of the subject’s visit. The CRFs are to be 
completed within reasonable time after the subject’s visit. The investigator must verify that all data 
entries in the CRFs are accurate and correct. If certain information is Not Done, Not Available or Not 
Applicable, the investigator must enter "N.D." or "N.AV." or "N.AP", respectively in the appropriate 
space.  
 
17. Direct access to source data/documents  
The investigator will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s), providing direct access to source data/documents.  
 
18. Data handling and record keeping  
The investigator essential documents will be retained for at least 20 years. At that moment, it will be 
judged whether it is necessary to retain them for a longer period, according to applicable regulatory 
or other requirement(s). 
 
19. References  
1. Dougados M, Baeten D. Spondyloarthritis. Lancet 2011;377(9783):2127-37. 
2. Mielants H, Veys EM, Cuvelier C et al. HLA-B27 related arthritis and bowel inflammation. Part 2. 
Ileocolonoscopy and bowel histology in patients with HLA-B27 related arthritis. J Rheumatol 1985;12-
294-8. 
3. Van Praet L, Van den Bosch F, Jacques P et al. Microscopic gut inflammation in axial 
spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis 2013;72:414-417. 
4. Van Praet L, Van den Bosch F, Mielants H, Elewaut D. Mucosal inflammation in spondyloarthritides: 
past, present and future. Curr Rheumatol Rep 2011;13(5):409-15. 
5. Mielants H, Veys EM, Cuvelier C, De Vos M. Course of gut inflammation in spondyloarthropathies 
and therapeutic consequences. Baillieres Clin Rheumatol 1996;10(1):147-64. 
6. Mielants H et al. The evolution of spondyloarthropathies in relation to gut histology. III. Relation 
between gut and joint. J Rheumatol 1995;22(12):2279-84. 
7. De Vos M, Mielants H, Cuvelier C, Elewaut A, Veys E. Long-term evolution of gut-inflammation in 
patients with spondyloarthropathy. Gastroenterology 1996;110(6):1696-703. 
8. Cypers H, Van Praet L, Varkas G, Elewaut D. Relevance of the gut/joint axis for the management of 
spondyloarthritis in daily clinical practice. Curr Opin Rheumatol 2014;26(4):371-6. 
9. Van Praet L et al. Degree of bone marrow edema in sacroiliac joints of patients with axial 
spondyloarthritis is linked to gut inflammation and male sex: results from the GIANT cohort. Ann 
Rheum Dis 2014;73(6):1186-9. 
10. Baert F et al. Mucosal healing predicts sustained clinical remission in patients with early-stage 
Crohn’s disease. Gastroenterology 2010;138(2):463-8. 


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11. van der Heijde D, Sieper J, Maksymowych W, Dougados M, Burgos-Vargas R, Landewé R et al. 
2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients 
with axial spondyloarthritis. Ann Rheum Dis 2011;70:905-8. 
12. Paccou J, Flipo RM. An appraisal of golimumab in the treatment of severe, active nonradiographic 
axial spondyloarthritis. Drug Des Devel Ther 2016;10:2255-62. 
13. Toussirot E, Vauchy C, Binda D, Michel F. Golimumab in radiographic and nonradiographic axial 
spondyloarthritis: a review of clinical trials. Drug Des Devel Ther 2016;10:2087-94. 
14. Sandborn W, Feagan B, Marano C, Zhang H, Strauss R, Johanns J et al. Subcutaneous golimumab 
induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. 
Gastroenterology 2014;146:85-95. 
15. Inman RD et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results 
of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 2008;58(11):3402-
12. 
16. Sieper J et al. A randomized, double-blind, placebo-controlled, sixteen-week study of 
subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis 
Rheumatol 2015;67(10):2702-12. 
17. Gossec et al. Preliminary definitions of ‘flare’ in axial spondyloarthritis, based on pain, BASDAI 
and ASDAS-CRP: an ASAS initiative. Ann Rheum Dis 2016;75(6):991-6. 
 
 


29 
 
Protocol Go Gut trial 
version 5.0 
19 January 2021 
Signature page 
 
Investigator: 
Name:  Prof. Dr Dirk Elewaut 
 
Title: 
Head of department Reumatologie – Principal Investigator 
 
 
Signature: 
 
Date:  
________________________________________________ 
 
 
Investigator: 
 
Name: Prof. Dr. Filip Van den Bosch 
________________________________________________ 
 
Title: 
Principal Investigator 
 
 
 
Signature: 
 
Date:  
________________________________________________