Clinical trial NCT01787786: Improving Treatment of Inflammatory Bowel Diseases Through Better Understanding Infliximab Drug and Antibody Levels
Official title: Defining and Predicting the Ideal Infliximab Pharmacokinetic Profile Associated With Treatment Efficacy in Patients With Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Crohn's Disease
Ulcerative Colitis
Keywords: Crohn's Disease
Ulcerative Colitis
Optimal Use of infliximab
Lead sponsor: University of Western Ontario, Canada
Sponsor class: OTHER
First posted: 2013-02-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 50 patients with Crohn's Disease and 50 patients with Ulcerative Colitis from 10 centres (Canada, United States, Netherlands and Spain).

Brief summary: The purpose of this study is to develop a predictive model that will allow optimized dosing of infliximab for individual patients

Detailed description: The use of pharmacokinetic analyses incorporating relevant determinants of the infliximab serum concentration can be used to develop a predictive model that will allow optimized dosing for individual patients.

Eligibility criteria: Inclusion Criteria:

* a diagnosis of CD or UC by usual criteria,
* moderate to severely active CD defined by a CDAI ≥ 220, with confirmed endoscopic activity (CDEIS ≥ 6) or moderate to severely active UC, defined by a Mayo Score ≥ 6, with a Mayo endoscopic subscore ≥ 2,
* a need for treatment with IFX for induction of remission as clinically indicated
* patients previously exposed to adalimumab and/or certolizumab who are naïve to infliximab will be allowed to participate.

Exclusion Criteria:

* perianal CD exclusively
* disease limited to the rectum in patients with UC (i.e., disease must extend ≥ 15 cm from the anal verge)
* patients with known antibodies to IFX (ADAs) at baseline
* a contraindication to infliximab therapy
* a contraindication to endoscopy
* an ostomy
* planned surgery
* evidence of severe or unstable hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, hematological or renal disease at the discretion of the investigator,
* Pregnancy or breastfeeding,
* treatment with any investigational drug in the past 30 days, or 5 half lives (whichever is longer).

Primary outcomes:
measure: Pharmacokinetic Analysis of Infliximab in patients with moderate to severely active ulcerative colitis and Crohn's Disease
timeFrame: 24 weeks
Secondary outcomes:
measure: Quantification of relative strengths of individual determinants of infliximab pharmacokinetics
timeFrame: 24 weeks
Other outcomes:
measure: Identification of patients at baseline that would benefit from receiving higher does of infliximab due to accelerated drug clearance
timeFrame: 24 weeks
Locations:
Study officials:
affiliation: Robarts Clinical Trials - Western University
name: Brian Feagan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
citation: Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9. doi: 10.1016/S0140-6736(02)08512-4.
citation: Reinisch W, Sandborn WJ, Rutgeerts P, Feagan BG, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Blank M, Lang Y, Johanns J, Colombel JF, Present D, Sands BE. Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies. Inflamm Bowel Dis. 2012 Feb;18(2):201-11. doi: 10.1002/ibd.21697. Epub 2011 Apr 11.
citation: Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am J Gastroenterol. 2009 Mar;104(3):760-7. doi: 10.1038/ajg.2008.88. Epub 2009 Jan 27.
citation: Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease. Clin Gastroenterol Hepatol. 2006 Oct;4(10):1248-54. doi: 10.1016/j.cgh.2006.06.025. Epub 2006 Aug 22.