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

21 février 2016 mis à jour par: Galapagos NV

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

  • 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.

Type d'étude

Interventionnel

Inscription (Réel)

175

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Berlin, Allemagne
        • DRK Clinics Berlin Westend
      • Frankfurt-am-Main, Allemagne
        • Interdisciplinary Crohn Colitis Center Rhein Main
      • Hamburg, Allemagne
        • Asklepios West Hospital Hamburg
      • Jena, Allemagne
        • University Hospital Jena
      • Kiel, Allemagne
        • University Hospital Schleswig-Holstein
      • Magdeburg, Allemagne
        • University Hospital Magdeburg
      • Minden, Allemagne
        • Gastroenterology Group Practice Minden
      • Oldenburg, Allemagne
        • Internal Medicine Group Practice Oldenburg
  • Belgique
      • Brussels, Belgique
        • St. Pierre University Hospital Center
      • Brussels, Belgique
        • University Hospital Saint Luc
      • Ghent, Belgique
        • University Hospital Ghent
      • Leuven, Belgique
        • University Hospitals Leuven
      • Liege, Belgique
        • CHR de la Citadelle
      • Liege, Belgique
        • Clinic Saint Joseph
  • 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
  • Fédération Russe
      • Barnaul, Fédération Russe
        • Territorial Clinical Hospital
      • Kazan, Fédération Russe
        • State Medical University
      • Krasnoyarsk, Fédération Russe
        • Territorial Clinical Hospital
      • Moscow, Fédération Russe
        • City Clinical Hospital #24
      • Moscow, Fédération Russe
        • A.N. Ryzhikh State Research Center for Coloproctology
      • Moscow, Fédération Russe
        • Moscow Clinical Research Center
      • Moscow, Fédération Russe
        • Vladimirsky Regional Clinical Research Institute
      • Nizhny Novgorod, Fédération Russe
        • Semashko Nizhny Novgorod Regional Clinical Hospital
      • Novosibirsk, Fédération Russe
        • City Clinical Hospital #12
      • Saint Petersburg, Fédération Russe
        • City Clinical Hospital #31
      • Saint Petersburg, Fédération Russe
        • First Pavlov State Medical University
      • Saint Petersburg, Fédération Russe
        • Mechnikov North-Western State Medical University
      • Saint Petersburg, Fédération Russe
        • St. Elizabeth City Hospital
  • Hongrie
      • Balatonfured, Hongrie
        • Drug Research Center Ltd.
      • Budapest, Hongrie
        • Semmelweis University
      • Budapest, Hongrie
        • ClinExpert Medical Center
      • Budapest, Hongrie
        • Szent Margit Hospital
      • Debrecen, Hongrie
        • University of Debrecen, Medical and Health Science Center
      • Gyula, Hongrie
        • Bekes County Pandy Kalman Hospital
      • Szekszard, Hongrie
        • Tolna County Balassa Janos Hospital
  • Pologne
      • Bydgoszcz, Pologne
        • Jan Biziel University Hospital #2
      • Lodz, Pologne
        • Saint Family Hospital Medical Center
      • Tychy, Pologne
        • H-T. Medical Center
      • Warsaw, Pologne
        • Maternal, Pediatric and Adolescent Healtcare Centre, Gastroenterology Diagnostic Facility for Adults
      • Warsaw, Pologne
        • Vivamed
      • Warsaw, Pologne
        • Clinical Hospital of Ministry of Internal Affairs and Administration
      • Wroclaw, Pologne
        • Active Health Center
  • Roumanie
      • Bucharest, Roumanie
        • Colentina Clinical Hospital
      • Bucharest, Roumanie
        • Fundeni Clinical Institute
      • Cluj-Napoca, Roumanie
        • Medical Center for Gastroenterology
      • Timisoara, Roumanie
        • Center for Gastroenterology, Ltd
  • Royaume-Uni
      • Birmingham, Royaume-Uni
        • Queen Elizabeth Hospital
      • Bournemouth, Royaume-Uni
        • Royal Bournemouth Hospital
      • Harrow, Royaume-Uni
        • St Mark's Hospital
      • Manchester, Royaume-Uni
        • Manchester Royal Infirmary
  • République tchèque
      • Hradec Kralove, République tchèque
        • Hepato-Gastroenterology HK Ltd.
      • Olomouc, République tchèque
        • University Hospital Olomouc
      • Pilsen, République tchèque
        • Outpatient Clinic of Internal Medicine and Gastroenterology
      • Prague, République tchèque
        • Institute of clinical and experimental medicine
      • Usti nad Labem, République tchèque
        • Masaryk's Hospital Usti Nad Labem
      • Znojmo, République tchèque
        • Hospital Znojmo

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La 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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: GLPG0634 200 mg QD
2 tablets of 100 mg GLPG0634 in the morning
Médicament: GLPG0634
100 mg oral tablet, intake once daily for 20 weeks
Autres noms:
  • Comprimés GLPG0634
Expérimental: GLPG0634 100 mg QD
1 tablet of 100 mg GLPG0634 and 1 placebo tablet in the morning
Médicament: GLPG0634
100 mg oral tablet, intake once daily for 20 weeks
Autres noms:
  • Comprimés GLPG0634
Médicament: Placebo
placebo oral tablets, intake once daily for 20 weeks
Autres noms:
  • Comprimés placebos
Comparateur placebo: Placebo QD
2 placebo tablets in the morning
Médicament: Placebo
placebo oral tablets, intake once daily for 20 weeks
Autres noms:
  • Comprimés placebos

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of subjects achieving clinical remission at Week 10
Délai: Week 10
Percentage of subjects achieving clinical remission as defined by a Crohn's Disease Activity Index score < 150 points
Week 10

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of subjects achieving clinical remission
Délai: 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
Up to Week 20
Percentage of subjects achieving clinical response
Délai: 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
Up to Week 20
Percentage of subjects achieving endoscopic remission at Week 10
Délai: 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
Délai: 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
Délai: 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
Délai: Up to Week 20
Change from Baseline in Crohn's Disease Activity Index score, assessed at every visit
Up to Week 20
Change from Screening in endoscopic score
Délai: Week 10
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
Délai: Week 10
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)
Délai: Up to Week 20
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
Délai: 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)
From screening up to 2 weeks after last dose
The number of subjects with abnormal lab tests
Délai: 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
From screening up to 2 weeks after last dose
The number of subjects with abnormal vital signs
Délai: 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
From screening up to 2 weeks after last dose
The number of subjects with abnormal ECG
Délai: 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)
From screening up to 2 weeks after last dose
The plasma levels of GLPG0634 and its metabolite
Délai: 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
Up to Week 20
The change versus Baseline in levels of immune- and inflammation-related parameters in whole blood and serum
Délai: 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
Up to Week 20
The change versus Baseline in levels of faecal calprotectin
Délai: Up to Week 20
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
Délai: 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
Up to Week 10

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Galapagos NV

Les enquêteurs

  • Directeur d'études: Pille Harrison, MD, Galapagos NV

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 février 2014

Achèvement primaire (Réel)

1 novembre 2015

Achèvement de l'étude (Réel)

1 février 2016

Dates d'inscription aux études

Première soumission

27 janvier 2014

Première soumission répondant aux critères de contrôle qualité

27 janvier 2014

Première publication (Estimation)

29 janvier 2014

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

23 février 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 février 2016

Dernière vérification

1 février 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • GLPG0634-CL-211
  • 2013-002857-32 (Numéro EudraCT)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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