Efficacy and Safety of GLPG0634 in Subjects With Active Crohn's Disease
- Registration Number
- NCT02048618
- Lead Sponsor
- Galapagos NV
- Brief Summary
* 180 patients suffering from active Crohn's disease with evidence of mucosal ulceration will be evaluated for improvement of disease activity (efficacy) when taking GLPG0634 or matching placebo once daily for 20 weeks in addition to their stable background treatment.
* During the course of the study, patients will also be examined for any side effects that may occur (safety and tolerability), and the amount of GLPG0634 present in the blood (Pharmacokinetics) as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood and stool (Pharmacodynamics) will be determined. Also, the effects GLPG0634 administration on subjects' quality of life will be evaluated.
- Detailed Description
* 180 patients suffering from active Crohn's disease with evidence of mucosal ulceration will be evaluated when taking GLPG0634 or matching placebo once daily in addition to their stable background treatment. The population will include 50% anti-TNF naïve patients and 50% of subjects previously exposed to anti-TNF.
* The study will consist of 2 parts, with total treatment duration of 20 weeks. Randomisation in Part 1 will be stratified according to subject's previous anti-TNF exposure, C-reactive protein (CRP) level at Screening and oral corticosteroid use at Day -1. However, at Week 10, subjects will be re-randomized automatically and stratified according to the subject's clinical response (reduction of Crohn's Disease Activity Index (CDAI) of 100 points), previous anti-TNF exposure and corticosteroid use at Day -1 to receive GLPG0634 200 mg q.d., 100 mg q.d. doses, or matching placebo q.d. in a blinded fashion. In Part 2, all will continue the study until Week 20.
* As efficacy parameters, the ability to achieve clinical response or remission, endoscopic response \& remission as well as mucosal healing with GLPG0634 given once daily compared to placebo will be evaluated after 10 weeks of treatment. In subjects who achieved clinical remission at Week 10, maintenance of the remission will be assessed during Part 2 of the study.
* During the course of the study, patients will also be examined for any side effects that may occur (safety and tolerability), and the amount of GLPG0634 present in the blood (Pharmacokinetics) as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood and stool (Pharmacodynamics) will be determined. Also, the effects of different doses and dose regimens of GLPG0634 administration on subjects' quality of life will be evaluated.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 175
- Male or female subjects between 18 and 75 years
- Documented history of ileal, colonic, or ileocolonic CD
- CDAI score ≥ 220 to ≤ 450
- Evidence of active inflammation as demonstrated by endoscopic confirmation of active disease
- Subjects previously not exposed to anti-TNF treatment (TNF-naïve) or subjects previously exposed to anti-TNF therapy at a registered dose, that has been discontinued at least 8 weeks prior to Screening and deemed by the treating physician as a primary or secondary non-responder or intolerant (TNF-experienced)
- Continuation of concurrent treatment with oral steroids (≤30 mg prednisolone eq/day), mesalazine, olsalazine, CD-related antibiotics and probiotics at stable dose is allowed
- Previous exposure to immunomodulators is permitted, but must be discontinued
- Haematology and biochemistry lab parameters within predefined ranges as stated in the protocol
- Diagnosis of indeterminate colitis, ulcerative colitis (UC), or clinical findings suggestive of UC
- Stoma, gastric or ileoanal pouch, procto- or total colectomy, symptomatic stenosis or obstructive strictures, history of bowel perforation, (suspected) abscess; actively draining fistulae
- Subject who has had surgical bowel resections within the past 6 months, short bowel syndrome or is receiving tube feeding, defined formula diets, or parenteral alimentation
- Subject with positive Clostridium difficile toxin stool assay or evidence of any other gastrointestinal infection
- Subject who has received non-permitted IBD therapies within specified timeframes, depending on the medication, as stated in the protocol
- Subject with a (previous history of) dysplasia of the gastrointestinal tract
- Concurrent gastro-intestinal malignancy or a history of cancer elsewhere
- History of lymphoproliferative disease
- Known active infection of any kind, current therapy for chronic infection or history of specific infections as stated in the protocol
- Subject who is pregnant, lactating or not willing to maintain highly effective birth control methods during the course of the study and 12 weeks thereafter
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo QD Placebo 2 placebo tablets in the morning GLPG0634 200 mg QD GLPG0634 2 tablets of 100 mg GLPG0634 in the morning GLPG0634 100 mg QD GLPG0634 1 tablet of 100 mg GLPG0634 and 1 placebo tablet in the morning GLPG0634 100 mg QD Placebo 1 tablet of 100 mg GLPG0634 and 1 placebo tablet in the morning
- Primary Outcome Measures
Name Time Method Percentage of subjects achieving clinical remission at Week 10 Week 10 Percentage of subjects achieving clinical remission as defined by a Crohn's Disease Activity Index score \< 150 points
- Secondary Outcome Measures
Name Time Method Percentage of subjects achieving mucosal healing at Week 10 Week 10 Percentage of subjects achieving mucosal healing as defined by a Simplified Endoscopy Score for Crohn's Disease (SES-CD) score equal to 0 at Week 10
Change from Screening in endoscopic score Week 10 Change from Screening in endoscopic Simplified Endoscopy Score for Crohn's Disease (SES-CD) score at Week 10
Change from Baseline in Subjects' Quality of Life (based on the Inflammatory Bowel Disease Questionnaire (IBDQ) questionnaire score) Up to Week 20 Change from Baseline in Subjects' Quality of Life based on the IBDQ questionnaire score at Week 10 and Week 20
Percentage of subjects achieving endoscopic remission at Week 10 Week 10 Percentage of subjects achieving endoscopic remission as defined by a reduction of Simplified Endoscopy Score for Crohn's Disease (SES-CD) score ≤ 4, with ulcerated surface subscore no greater than 1 in any segment at Week 10
The number of subjects with abnormal lab tests From screening up to 2 weeks after last dose To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms laboratory test abnormalities
The number of subjects with abnormal vital signs From screening up to 2 weeks after last dose To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of abnormalities in vital signs
The change versus Baseline in levels of immune- and inflammation-related parameters in whole blood and serum Up to Week 20 To characterize the pharmacodynamics (PD) of GLPG0634 and its metabolite by measuring the levels of immune- and inflammation-related parameters in whole blood and serum
Change from Screening in histopathology biopsy score Week 10 Change from Screening in histopathology biopsy score at Week 10
The number of subjects with adverse events From screening up to 2 weeks after last dose To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs)
Percentage of subjects achieving clinical response Up to Week 20 Percentage of subjects achieving clinical response as defined by a decrease in Crohn's Disease Activity Index score of at least 100 points, assessed at every visit
The number of subjects with abnormal ECG From screening up to 2 weeks after last dose To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of abnormalities in electrocardiogram (ECG)
Percentage of subjects achieving clinical remission Up to Week 20 Percentage of subjects achieving clinical remission as defined by a Crohn's Disease Activity Index score \< 150 points, assessed at every visit
Percentage of subjects achieving endoscopic response at Week 10 Week 10 Percentage of subjects achieving endoscopic response as defined by a reduction of Simplified Endoscopy Score for Crohn's Disease (SES-CD) score by at least 50% from Screening at Week 10
Change from Baseline in Crohn's Disease Activity Index score Up to Week 20 Change from Baseline in Crohn's Disease Activity Index score, assessed at every visit
The change versus Baseline in microbial communities in stool samples Up to Week 10 To characterize the effects of GLPG0634 and its metabolite on the microbial communities by measuring the levels of predominant microbiota in stool samples
The change versus Baseline in levels of faecal calprotectin Up to Week 20 To characterize the pharmacodynamics (PD) of GLPG0634 and its metabolite by measuring the levels of faecal calprotectin
The plasma levels of GLPG0634 and its metabolite Up to Week 20 To characterize the pharmacokinetics (PK) of GLPG0634 and its metabolite by measuring the amount in plasma from Week 2 up to Week 20 at every visit
Trial Locations
- Locations (62)
Szent Margit Hospital
🇭🇺Budapest, Hungary
Hospital Gabriel Montpied
🇫🇷Clermont-Ferrand, France
University Hospital Jena
🇩🇪Jena, Germany
University Hospital Magdeburg
🇩🇪Magdeburg, Germany
Beaujon Hospital
🇫🇷Clichy, France
University Hospital Schleswig-Holstein
🇩🇪Kiel, Germany
Asklepios West Hospital Hamburg
🇩🇪Hamburg, Germany
Interdisciplinary Crohn Colitis Center Rhein Main
🇩🇪Frankfurt-am-Main, Germany
DRK Clinics Berlin Westend
🇩🇪Berlin, Germany
Archet Hospital
🇫🇷Nice, France
Saint Etienne University Hospital Center
🇫🇷Saint Etienne, France
St Mark's Hospital
🇬🇧Harrow, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Dijon University Hospital Center
🇫🇷Dijon, France
Hospital Michallon
🇫🇷Grenoble, France
Lille Regional University Hospital Center
🇫🇷Lille, France
University Hospital Ghent
🇧🇪Ghent, Belgium
Clinic Saint Joseph
🇧🇪Liege, Belgium
Hepato-Gastroenterology HK Ltd.
🇨🇿Hradec Kralove, Czech Republic
North Hospital
🇫🇷Marseille, France
Clinexpert Medical Center
🇭🇺Budapest, Hungary
Semmelweis University
🇭🇺Budapest, Hungary
Saint Family Hospital Medical Center
🇵🇱Lodz, Poland
Territorial Clinical Hospital
🇷🇺Krasnoyarsk, Russian Federation
State Medical University
🇷🇺Kazan, Russian Federation
Active Health Center
🇵🇱Wroclaw, Poland
University Hospital Saint Luc
🇧🇪Brussels, Belgium
St. Pierre University Hospital Center
🇧🇪Brussels, Belgium
Institute of Clinical and Experimental Medicine
🇨🇿Prague, Czech Republic
Drug Research Center Ltd.
🇭🇺Balatonfured, Hungary
University Hospitals Leuven
🇧🇪Leuven, Belgium
CHR de la Citadelle
🇧🇪Liege, Belgium
University Hospital Olomouc
🇨🇿Olomouc, Czech Republic
Masaryk's Hospital Usti Nad Labem
🇨🇿Usti nad Labem, Czech Republic
Colentina Clinical Hospital
🇷🇴Bucharest, Romania
Outpatient Clinic of Internal Medicine and Gastroenterology
🇨🇿Pilsen, Czech Republic
H-T. Medical Center
🇵🇱Tychy, Poland
Maternal, Pediatric and Adolescent Healtcare Centre, Gastroenterology Diagnostic Facility for Adults
🇵🇱Warsaw, Poland
Hospital Znojmo
🇨🇿Znojmo, Czech Republic
University of Debrecen, Medical and Health Science Center
🇭🇺Debrecen, Hungary
Bekes County Pandy Kalman Hospital
🇭🇺Gyula, Hungary
Clinical Hospital of Ministry of Internal Affairs and Administration
🇵🇱Warsaw, Poland
Tolna County Balassa Janos Hospital
🇭🇺Szekszard, Hungary
Jan Biziel University Hospital #2
🇵🇱Bydgoszcz, Poland
Vivamed
🇵🇱Warsaw, Poland
A.N. Ryzhikh State Research Center for Coloproctology
🇷🇺Moscow, Russian Federation
Vladimirsky Regional Clinical Research Institute
🇷🇺Moscow, Russian Federation
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Center for Gastroenterology, Ltd
🇷🇴Timisoara, Romania
Mechnikov North-Western State Medical University
🇷🇺Saint Petersburg, Russian Federation
St. Elizabeth City Hospital
🇷🇺Saint Petersburg, Russian Federation
Medical Center for Gastroenterology
🇷🇴Cluj-Napoca, Romania
Moscow Clinical Research Center
🇷🇺Moscow, Russian Federation
Semashko Nizhny Novgorod Regional Clinical Hospital
🇷🇺Nizhny Novgorod, Russian Federation
City Clinical Hospital #12
🇷🇺Novosibirsk, Russian Federation
City Clinical Hospital #31
🇷🇺Saint Petersburg, Russian Federation
First Pavlov State Medical University
🇷🇺Saint Petersburg, Russian Federation
Gastroenterology Group Practice Minden
🇩🇪Minden, Germany
Internal Medicine Group Practice Oldenburg
🇩🇪Oldenburg, Germany
City Clinical Hospital #24
🇷🇺Moscow, Russian Federation
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom