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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02048618
• Other study ID #: GLPG0634-CL-211
• Secondary ID: 2013-002857-32
• Status: Completed
• Phase: Phase 2
• First received: January 27, 2014
• Last updated: February 21, 2016
• Start date: February 2014
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPCzech Republic: State Institute for Drug ControlFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: February 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• GLPG0634
100 mg oral tablet, intake once daily for 20 weeks
• Placebo
placebo oral tablets, intake once daily for 20 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Belgium,  Czech Republic,  France,  Germany,  Hungary,  Poland,  Romania,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change from Screening in histopathology biopsy score	Change from Screening in histopathology biopsy score at Week 10	Week 10	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No