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Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143)

14 septembre 2018 mis à jour par: Merck Sharp & Dohme LLC

An Open Label Study to Discover Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (CD)

This study will evaluate biomarkers that reflect changes in gut mucosal status during therapy with infliximab and determine whether changes in the levels of the selected biomarkers can be used to predict endoscopically assessed gut mucosal status changes.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Observationnel

Inscription (Réel)

15

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 60 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

Approximately 20 participants aged 18 to 60 years with Crohn's Disease will be enrolled from gastrointestinal specialist clinics.

La description

Inclusion Criteria:

  • Clinical diagnosis of Crohn's Disease (CD) of at least 6 weeks duration, or acute diagnosis of sufficiently severe CD warranting initiation of infliximab sooner than allowed by fecal calprotectin turnaround time
  • History of colonic involvement verified by prior endoscopy or radiography
  • Indicated for treatment with infliximab according to current best medical practice
  • Body Mass Index (BMI) between 15 kg/m^2 and 35 kg/m^2
  • Women of childbearing potential and non-vasectomized men agree to use medically-acceptable contraception
  • Negative pregnancy test
  • No signs or symptoms of active tuberculosis (TB) and has a negative TB test within 6 weeks of first study drug administration

Exclusion Criteria:

  • Pregnancy, intention to become pregnant, or breastfeeding
  • Evidence of a colon unaffected by CD
  • Indication for surgery
  • Perianal disease likely to interfere with study participation
  • Presence of a stoma or history of colectomy
  • Symptomatic diarrhea unrelated to CD
  • Strictures or evidence of bowel obstruction
  • Presence of abscess unless completed definitive treatment can be documented one week prior to screening
  • Presence of fistulas
  • Contraindication to infliximab
  • Intolerance to sedatives or other medications required for endoscopy
  • Any prior use of anti-inflammatory biologic therapy
  • Moderate or severe congestive heart failure
  • History of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
  • Major surgery or donation/loss of at least one unit of blood within 4 weeks of screening
  • Positive for hepatitis B surface antigen, hepatitis C antibodies, or Human Immunodeficiency Virus (HIV)
  • History of any tumor except adequately treated basal cell carcinoma or carcinoma in situ of the cervix
  • History of systemic granulomatous infection
  • History of nontuberculous mycobacterial disease, or any opportunistic infection within 12 months of study entry
  • Transplanted organ including bone marrow or hematopoietic stem cell-derived marrow

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

  • Modèles d'observation: Cohorte
  • Perspectives temporelles: Éventuel

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
Infliximab 5 mg/kg
Infliximab treatment and endoscopy.
Médicament: Infliximab
Infliximab administered intravenously at a dose of 5 mg/kg at study Weeks 0, 2, 6, 14, and 22.
Autres noms:
  • Rémicade
  • SCH 215596
  • MK-2155

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6
Délai: Baseline and Week 6
CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 6 minus baseline CDEIS scores, with a negative change from baseline indicating improvement.
Baseline and Week 6
Change From Baseline in CDEIS Blinded Score at Week 22
Délai: Baseline and Week 22
CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 22 minus baseline CDEIS scores, with a negative change from baseline indicating improvement.
Baseline and Week 22
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6
Délai: Baseline and Week 6
Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.
Baseline and Week 6
Change From Baseline in Serum hsCRP at Week 22
Délai: Baseline and Week 22
Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.
Baseline and Week 22
Change From Baseline in Stool Calprotectin at Week 6
Délai: Baseline and Week 6
Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.
Baseline and Week 6
Change From Baseline in Stool Calprotectin at Week 22
Délai: Baseline and Week 22
Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.
Baseline and Week 22
Change From Baseline in Serum Lipocalin-2 at Week 6
Délai: Baseline and Week 6
Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.
Baseline and Week 6
Change From Baseline in Serum Lipocalin-2 at Week 22
Délai: Baseline and Week 22
Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.
Baseline and Week 22
Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6
Délai: Baseline and Week 6
Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.
Baseline and Week 6
Change From Baseline in REG3-A at Week 22
Délai: Baseline and Week 22
Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.
Baseline and Week 22
Coefficient of Determination (R^2) For Predicting The Change From Baseline In Blinded CDEIS Score From The Changes From Baseline In Four Biomarkers At Weeks 6 and 22
Délai: Baseline and Week 6 or 22
To determine R^2 a multiple linear regression analysis was conducted with the change from baseline in CDEIS score as the response variable and the baseline CDEIS score, changes from baseline in the four biomarkers serum hsCRP, serum lipocalin-2, serum Reg3-A, and stool calprotectin (their concentrations were log-transformed to make the mean function of the response more linear) at Weeks 6 and 22 as the predictor variables. CDEIS scores were provided by a blinded observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy. The R^2 can range from 0 to 1; with higher values indicating greater predictability of the model. The primary hypothesis is that the true R^2 at weeks 6 and 22 is approximately 0.7.
Baseline and Week 6 or 22

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers
Délai: Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)
Based on two measurements at baseline, the concordance correlation coefficient (CCC) was computed for each of four biomarkers, using a mixed effects model with a fixed factor for repeat measurements and a random factor for participant. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements.
Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)
Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation
Délai: Baseline, Week 6, Week 22
The CCC of blinded (central) versus unblinded (site) scores from either CDEIS or the Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined at Baseline, Week 6 and Week 22. SES-CD sums the following scores: presence and size of ulcers in five visualized bowel segments; extent of ulcerated surface in five visualized bowel segments; extent of affected surface in five visualized bowel segments; presence and type of narrowings in five visualized bowel segments; and can range from 0-56, with a higher sum indicating greater severity of mucosal inflammation. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements.
Baseline, Week 6, Week 22

Collaborateurs et enquêteurs

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

Parrainer

Merck Sharp & Dohme LLC

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 (Réel)

28 novembre 2012

Achèvement primaire (Réel)

28 septembre 2015

Achèvement de l'étude (Réel)

28 septembre 2015

Dates d'inscription aux études

Première soumission

5 mai 2011

Première soumission répondant aux critères de contrôle qualité

6 mai 2011

Première publication (Estimation)

9 mai 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

15 octobre 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

14 septembre 2018

Dernière vérification

1 septembre 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • P08143
  • 2011-000517-40 (Numéro EudraCT)
  • MK-2155-195

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

Oui

Description du régime IPD

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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