Efficacy and Safety of GLPG0634 in Subjects With Active Crohn's Disease

Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Study to Investigate the Efficacy and Safety of GLPG0634 in Subjects With Active Crohn's Disease With Evidence of Mucosal Ulceration

• 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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: GLPG0634; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • St. Pierre University Hospital Center
  • Brussels, Belgium
    • University Hospital Saint Luc
  • Ghent, Belgium
    • University Hospital Ghent
  • Leuven, Belgium
    • University Hospitals Leuven
  • Liege, Belgium
    • Chr de La Citadelle
  • Liege, Belgium
    • Clinic Saint Joseph
• Czech Republic
  • Hradec Kralove, Czech Republic
    • Hepato-Gastroenterology HK Ltd.
  • Olomouc, Czech Republic
    • University Hospital Olomouc
  • Pilsen, Czech Republic
    • Outpatient Clinic of Internal Medicine and Gastroenterology
  • Prague, Czech Republic
    • Institute of Clinical and Experimental Medicine
  • Usti nad Labem, Czech Republic
    • Masaryk's Hospital Usti Nad Labem
  • Znojmo, Czech Republic
    • Hospital Znojmo
• France
  • Clermont-Ferrand, France
    • Hospital Gabriel Montpied
  • Clichy, France
    • Beaujon Hospital
  • Dijon, France
    • Dijon University Hospital Center
  • Grenoble, France
    • Hospital Michallon
  • Lille, France
    • Lille Regional University Hospital Center
  • Marseille, France
    • North Hospital
  • Nice, France
    • Archet Hospital
  • Saint Etienne, France
    • Saint Etienne University Hospital Center
• Germany
  • Berlin, Germany
    • DRK Clinics Berlin Westend
  • Frankfurt-am-Main, Germany
    • Interdisciplinary Crohn Colitis Center Rhein Main
  • Hamburg, Germany
    • Asklepios West Hospital Hamburg
  • Jena, Germany
    • University Hospital Jena
  • Kiel, Germany
    • University Hospital Schleswig-Holstein
  • Magdeburg, Germany
    • University Hospital Magdeburg
  • Minden, Germany
    • Gastroenterology Group Practice Minden
  • Oldenburg, Germany
    • Internal Medicine Group Practice Oldenburg
• Hungary
  • Balatonfured, Hungary
    • Drug Research Center Ltd.
  • Budapest, Hungary
    • Semmelweis University
  • Budapest, Hungary
    • ClinExpert Medical Center
  • Budapest, Hungary
    • Szent Margit Hospital
  • Debrecen, Hungary
    • University of Debrecen, Medical and Health Science Center
  • Gyula, Hungary
    • Bekes County Pandy Kalman Hospital
  • Szekszard, Hungary
    • Tolna County Balassa János Hospital
• Poland
  • Bydgoszcz, Poland
    • Jan Biziel University Hospital #2
  • Lodz, Poland
    • Saint Family Hospital Medical Center
  • Tychy, Poland
    • H-T. Medical Center
  • Warsaw, Poland
    • Maternal, Pediatric and Adolescent Healtcare Centre, Gastroenterology Diagnostic Facility for Adults
  • Warsaw, Poland
    • Vivamed
  • Warsaw, Poland
    • Clinical Hospital of Ministry of Internal Affairs and Administration
  • Wroclaw, Poland
    • Active Health Center
• Romania
  • Bucharest, Romania
    • Colentina Clinical Hospital
  • Bucharest, Romania
    • Fundeni Clinical Institute
  • Cluj-Napoca, Romania
    • Medical Center for Gastroenterology
  • Timisoara, Romania
    • Center for Gastroenterology, Ltd
• Russian Federation
  • Barnaul, Russian Federation
    • Territorial Clinical Hospital
  • Kazan, Russian Federation
    • State Medical University
  • Krasnoyarsk, Russian Federation
    • Territorial Clinical Hospital
  • Moscow, Russian Federation
    • City Clinical Hospital #24
  • Moscow, Russian Federation
    • A.N. Ryzhikh State Research Center for Coloproctology
  • Moscow, Russian Federation
    • Moscow Clinical Research Center
  • Moscow, Russian Federation
    • Vladimirsky Regional Clinical Research Institute
  • Nizhny Novgorod, Russian Federation
    • Semashko Nizhny Novgorod Regional Clinical Hospital
  • Novosibirsk, Russian Federation
    • City Clinical Hospital #12
  • Saint Petersburg, Russian Federation
    • City Clinical Hospital #31
  • Saint Petersburg, Russian Federation
    • First Pavlov State Medical University
  • Saint Petersburg, Russian Federation
    • Mechnikov North-Western State Medical University
  • Saint Petersburg, Russian Federation
    • St. Elizabeth City Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Harrow, United Kingdom
    • St Mark's Hospital
  • Manchester, United Kingdom
    • Manchester Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLPG0634 200 mg QD; 2 tablets of 100 mg GLPG0634 in the morning	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 20 weeks; Other Names: GLPG0634 tablets
Experimental: GLPG0634 100 mg QD; 1 tablet of 100 mg GLPG0634 and 1 placebo tablet in the morning	Drug: GLPG0634; 100 mg oral tablet, intake once daily for 20 weeks; Other Names: GLPG0634 tablets; Drug: Placebo; placebo oral tablets, intake once daily for 20 weeks; Other Names: Placebo tablets
Placebo Comparator: Placebo QD; 2 placebo tablets in the morning	Drug: Placebo; placebo oral tablets, intake once daily for 20 weeks; Other Names: Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects achieving clinical remission at Week 10	Percentage of subjects achieving clinical remission as defined by a Crohn's Disease Activity Index score < 150 points	Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects achieving clinical remission	Percentage of subjects achieving clinical remission as defined by a Crohn's Disease Activity Index score < 150 points, assessed at every visit	Up to Week 20
Percentage of subjects achieving clinical response	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	Up to Week 20
Percentage of subjects achieving endoscopic remission at 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	Week 10
Percentage of subjects achieving endoscopic response at 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	Week 10
Percentage of subjects achieving mucosal healing at 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	Week 10
Change from Baseline in Crohn's Disease Activity Index score	Change from Baseline in Crohn's Disease Activity Index score, assessed at every visit	Up to Week 20
Change from Screening in endoscopic score	Change from Screening in endoscopic Simplified Endoscopy Score for Crohn's Disease (SES-CD) score at Week 10	Week 10
Change from Screening in histopathology biopsy score	Change from Screening in histopathology biopsy score at Week 10	Week 10
Change from Baseline in Subjects' Quality of Life (based on the Inflammatory Bowel Disease Questionnaire (IBDQ) questionnaire score)	Change from Baseline in Subjects' Quality of Life based on the IBDQ questionnaire score at Week 10 and Week 20	Up to Week 20
The number of subjects with adverse events	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs)	From screening up to 2 weeks after last dose
The number of subjects with abnormal lab tests	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms laboratory test abnormalities	From screening up to 2 weeks after last dose
The number of subjects with abnormal vital signs	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of abnormalities in vital signs	From screening up to 2 weeks after last dose
The number of subjects with abnormal ECG	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of abnormalities in electrocardiogram (ECG)	From screening up to 2 weeks after last dose
The plasma levels of GLPG0634 and its metabolite	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	Up to Week 20
The change versus Baseline in levels of immune- and inflammation-related parameters in whole blood and serum	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	Up to Week 20
The change versus Baseline in levels of faecal calprotectin	To characterize the pharmacodynamics (PD) of GLPG0634 and its metabolite by measuring the levels of faecal calprotectin	Up to Week 20
The change versus Baseline in microbial communities in stool samples	To characterize the effects of GLPG0634 and its metabolite on the microbial communities by measuring the levels of predominant microbiota in stool samples	Up to Week 10

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Pille Harrison, MD, Galapagos NV

Publications and helpful links

General Publications

• Vermeire S, Schreiber S, Petryka R, Kuehbacher T, Hebuterne X, Roblin X, Klopocka M, Goldis A, Wisniewska-Jarosinska M, Baranovsky A, Sike R, Stoyanova K, Tasset C, Van der Aa A, Harrison P. Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet. 2017 Jan 21;389(10066):266-275. doi: 10.1016/S0140-6736(16)32537-5. Epub 2016 Dec 15.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 27, 2014
• First Posted (Estimate): January 29, 2014

Study Record Updates

• Last Update Posted (Estimate): February 23, 2016
• Last Update Submitted That Met QC Criteria: February 21, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Active Crohn's Disease; GLPG0634
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GLPG0634-CL-211; 2013-002857-32 (EudraCT Number)