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

Conditions

Crohn's Disease

Keywords

Active Crohn's Disease, GLPG0634

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.

Christopher Ma, Brian G. Feagan, Zhongya Wang, Guangyong Zou, Michelle I. Smith et al. (11 authors)

Journal of Crohn s and Colitis2024-07-203 citations

10.1093/ecco-jcc/jjae113

Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn’s Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial

Walter Reinisch, Jean‐Frédéric Colombel, Geert D’Haens, Jordi Rimola, Tomasz Masior et al. (10 authors)

Journal of Crohn s and Colitis2024-02-1622 citations

10.1093/ecco-jcc/jjae003

Mucosal p-STAT1/3 correlates with histologic disease activity in Crohn’s disease and is responsive to filgotinib

Walter Reinisch, Adrian Serone, Xavier Hébuterne, Tanja Kühbacher, Maria Kłopocka et al. (14 authors)

Tissue Barriers2022-06-283 citations

10.1080/21688370.2022.2088961

P117 Filgotinib reduces markers of JAK1 signaling in Crohn’s disease: concordance with endoscopy and histopathology

Jason Goh, Walter Reinisch, Jens Brodbeck, René Galien, Ethan Grant et al. (14 authors)

2021-01-01

10.1136/gutjnl-2020-bsgcampus.192

P535 Effects of the Janus Kinase 1 (JAK1)-selective inhibitor filgotinib on circulating cytokines and whole-blood genes/pathways of patients with moderately to severely active Crohn’s disease (CD)

Xavier Roblin, Adrian Serone, O. K. Yoon, Longcai Zhuo, Ethan Grant et al. (9 authors)

Journal of Crohn s and Colitis2020-01-012 citations

10.1093/ecco-jcc/jjz203.663

P418 Filgotinib decreases molecular markers of JAK1 signal transduction in Crohn’s disease: concordance with endoscopy and histopathology

Walter Reinisch, Jens Brodbeck, René Galien, Ethan Grant, Xavier Hébuterne et al. (13 authors)

Journal of Crohn s and Colitis2020-01-01

10.1093/ecco-jcc/jjz203.547

PTU-003 Filgotinib decreases inflammatory markers associated with endoscopic improvement in moderate to severely active crohn’s disease

Satish Keshav, Xavier Roblin, Geert D’Haens, René Galien, Lovely Goyal et al. (12 authors)

2018-06-011 citations

10.1136/gutjnl-2018-bsgabstracts.125

P643 Filgotinib decreases systemic and mucosal markers of inflammation that are associated with endoscopic improvement in moderately to severely active Crohn’s disease patients

Xavier Roblin, Geert D’Haens, René Galien, Lovely Goyal, W Li et al. (11 authors)

Journal of Crohn s and Colitis2018-01-16

10.1093/ecco-jcc/jjx180.770

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.

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.

2016-12-15325 citations

10.1016/s0140-6736(16)32537-5

Interventions

DRUGGLPG0634

100 mg oral tablet, intake once daily for 20 weeks

DRUGPlacebo

placebo oral tablets, intake once daily for 20 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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
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 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
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 Screening in histopathology biopsy score	Week 10	Change from Screening in histopathology biopsy 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 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
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 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)
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
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
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 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 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)

Countries

Belgium, Czechia, France, Germany, Hungary, Poland, Romania, Russia, United Kingdom

Outcome results

None listed