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

Study Overview
=================
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.

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

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Drug: GLPG0634
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Active Crohn's Disease, GLPG0634