Clinical trial NCT02048618: Efficacy and Safety of GLPG0634 in Subjects With Active Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: Active Crohn's Disease
GLPG0634
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2014-01-29
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of subjects achieving clinical remission at Week 10
timeFrame: Week 10
Secondary outcomes:
measure: Percentage of subjects achieving clinical remission
timeFrame: Up to Week 20
measure: Percentage of subjects achieving clinical response
timeFrame: Up to Week 20
measure: Percentage of subjects achieving endoscopic remission at Week 10
timeFrame: Week 10
measure: Percentage of subjects achieving endoscopic response at Week 10
timeFrame: Week 10
measure: Percentage of subjects achieving mucosal healing at Week 10
timeFrame: Week 10
measure: Change from Baseline in Crohn's Disease Activity Index score
timeFrame: Up to Week 20
measure: Change from Screening in endoscopic score
timeFrame: Week 10
measure: Change from Screening in histopathology biopsy score
timeFrame: Week 10
measure: Change from Baseline in Subjects' Quality of Life (based on the Inflammatory Bowel Disease Questionnaire (IBDQ) questionnaire score)
timeFrame: Up to Week 20
measure: The number of subjects with adverse events
timeFrame: From screening up to 2 weeks after last dose
measure: The number of subjects with abnormal lab tests
timeFrame: From screening up to 2 weeks after last dose
measure: The number of subjects with abnormal vital signs
timeFrame: From screening up to 2 weeks after last dose
measure: The number of subjects with abnormal ECG
timeFrame: From screening up to 2 weeks after last dose
measure: The plasma levels of GLPG0634 and its metabolite
timeFrame: Up to Week 20
measure: The change versus Baseline in levels of immune- and inflammation-related parameters in whole blood and serum
timeFrame: Up to Week 20
measure: The change versus Baseline in levels of faecal calprotectin
timeFrame: Up to Week 20
measure: The change versus Baseline in microbial communities in stool samples
timeFrame: Up to Week 10
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: St. Pierre University Hospital Center
city: Brussels
country: Belgium
facility: University Hospital Saint Luc
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Liege
country: Belgium
facility: CHR de la Citadelle
city: Liege
country: Belgium
facility: Clinic Saint Joseph
city: Hradec Kralove
country: Czech Republic
facility: Hepato-Gastroenterology HK Ltd.
city: Olomouc
country: Czech Republic
facility: University Hospital Olomouc
city: Pilsen
country: Czech Republic
facility: Outpatient Clinic of Internal Medicine and Gastroenterology
city: Prague
country: Czech Republic
facility: Institute of Clinical and Experimental Medicine
city: Usti nad Labem
country: Czech Republic
facility: Masaryk's Hospital Usti Nad Labem
city: Znojmo
country: Czech Republic
facility: Hospital Znojmo
city: Clermont-Ferrand
country: France
facility: Hospital Gabriel Montpied
city: Clichy
country: France
facility: Beaujon Hospital
city: Dijon
country: France
facility: Dijon University Hospital Center
city: Grenoble
country: France
facility: Hospital Michallon
city: Lille
country: France
facility: Lille Regional University Hospital Center
city: Marseille
country: France
facility: North Hospital
city: Nice
country: France
facility: Archet Hospital
city: Saint Etienne
country: France
facility: Saint Etienne University Hospital Center
city: Berlin
country: Germany
facility: DRK Clinics Berlin Westend
city: Frankfurt-am-Main
country: Germany
facility: Interdisciplinary Crohn Colitis Center Rhein Main
city: Hamburg
country: Germany
facility: Asklepios West Hospital Hamburg
city: Jena
country: Germany
facility: University Hospital Jena
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Magdeburg
country: Germany
facility: University Hospital Magdeburg
city: Minden
country: Germany
facility: Gastroenterology Group Practice Minden
city: Oldenburg
country: Germany
facility: Internal Medicine Group Practice Oldenburg
city: Balatonfured
country: Hungary
facility: Drug Research Center Ltd.
city: Budapest
country: Hungary
facility: Clinexpert Medical Center
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: Szent Margit Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen, Medical and Health Science Center
city: Gyula
country: Hungary
facility: Bekes County Pandy Kalman Hospital
city: Szekszard
country: Hungary
facility: Tolna County Balassa Janos Hospital
city: Bydgoszcz
country: Poland
facility: Jan Biziel University Hospital #2
city: Lodz
country: Poland
facility: Saint Family Hospital Medical Center
city: Tychy
country: Poland
facility: H-T. Medical Center
city: Warsaw
country: Poland
facility: Clinical Hospital of Ministry of Internal Affairs and Administration
city: Warsaw
country: Poland
facility: Maternal, Pediatric and Adolescent Healtcare Centre, Gastroenterology Diagnostic Facility for Adults
city: Warsaw
country: Poland
facility: Vivamed
city: Wroclaw
country: Poland
facility: Active Health Center
city: Bucharest
country: Romania
facility: Colentina Clinical Hospital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Cluj-Napoca
country: Romania
facility: Medical Center for Gastroenterology
city: Timisoara
country: Romania
facility: Center for Gastroenterology, Ltd
city: Barnaul
country: Russian Federation
facility: Territorial Clinical Hospital
city: Kazan
country: Russian Federation
facility: State Medical University
city: Krasnoyarsk
country: Russian Federation
facility: Territorial Clinical Hospital
city: Moscow
country: Russian Federation
facility: A.N. Ryzhikh State Research Center for Coloproctology
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #24
city: Moscow
country: Russian Federation
facility: Moscow Clinical Research Center
city: Moscow
country: Russian Federation
facility: Vladimirsky Regional Clinical Research Institute
city: Nizhny Novgorod
country: Russian Federation
facility: Semashko Nizhny Novgorod Regional Clinical Hospital
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital #12
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Hospital #31
city: Saint Petersburg
country: Russian Federation
facility: First Pavlov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Mechnikov North-Western State Medical University
city: Saint Petersburg
country: Russian Federation
facility: St. Elizabeth City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Harrow
country: United Kingdom
facility: St Mark's Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: Galapagos NV
name: Pille Harrison, MD
role: STUDY_DIRECTOR
References:
citation: 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.