The degradation and elimination of Infliximab

• Conditions: Inflammatory bowel disease (Ulcerative Colitis, Crohn's disease); MedDRA version: 17.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; MedDRA version: 17.0Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2011-001332-29-AT
• Lead Sponsor: niversitätsklinik für Innere Medizin III, Klinische Abteilung für Gastroenterologie und Hepatologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-07
• Last Update Posted: 27 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Patients with established diagnosis of Crohn’s disease or ulcerative colitis by standard criteria for at least 3 months between the age of 19 to 75. Males and females.
2.Able and willing to sign informed consent
3.For maintenance cohort: Patients with maintenance Infliximab therapy after having received week 0, 2 and 6 infusions. Earliest possible measurement for trough level being Week 14 (immediately prior to 4th infusion), earliest possible week 4 serum infliximab level measurement at infusion week 10.
4.For infliximab starter cohort: Patients planned for IFX induction and maintenance therapy according to current guidelines without prior exposition to IFX.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1.History of malignancy, lymphoproliferativen disorders or untreated or unsuccessfully treated cutaneous squamous cell or basal cell carcinoma or carcinoma-in-situ of the cervix.
2.Active or untreated latent tuberculosis, as diagnosed by the current screening recommendations
3.Severe infections, sepsis, abscess or opportunistic infections
4.Subjects with an oostomy or ileoanal pouch
5.Signs and symptoms of intestinal obstruction, clinically or indicated by imaging (praestenotic dilatation, significant prolongation of transition time, ileus signs)
6.Impending or planned surgery for condition under study
7.Heart failure NYHA class 3 and 4
8.Severe unstable hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, hematological or renal disease
9.Pregnacy, planning conception or currently breast feeding
10.Investigational agents within 5 halfe lives prior to entry or within the past 30 days
11.Sigificant drug or alcohol abusus, current or past, or other mental condition impairing study participation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess pharmacokinetics of Infliximab in routinely treated patients with inflammatory bowel disease (Crohn's disease, Ulcerative Colitis);Secondary Objective: not applicable;Primary end point(s): Difference of measured serum infliximab levels at week 4 during maintenance infusion interval and immediately prior to infusion (trough level) versus predicted levels, as calculated by prediction model (see Methods).;Timepoint(s) of evaluation of this end point: not applicable

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Rate of mucosal healing in patients with trough levels above 3 µg/ml during maintenance versus trough levels below 3 µg/ml<br>•Rate of steroid free clinical remission in patients with trough levels above 3 µg/ml during maintenance<br>•Fecal Calprotectin, CRP, CD64, IL-6 in patients with rapid elimination kinetics vs. slow elimination at the time points as specified below<br>•Rate of primary remission in CD patients<br>•Rate of primary response in CD patients<br>•Rate of primary remission in UC patients<br>•Rate of primary response in UC patients<br>•Comparison pharmacokinetic properties (c-max, terminal half-life, AUC, clearance) of patients with primary response vs. primary non-responders and patients in remission<br>•Rate of disease worsening<br>•Comparison of pk properties at time of disease worsening (prior infusion interval while responding versus current infusion interval)<br>;Timepoint(s) of evaluation of this end point: not applicable