Improving Treatment of Inflammatory Bowel Diseases Through Better Understanding Infliximab Drug and Antibody Levels

Ulcerative Colitis Clinical Trial

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Official title:

Defining and Predicting the Ideal Infliximab Pharmacokinetic Profile Associated With Treatment Efficacy in Patients With Inflammatory Bowel Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01787786
• Other study ID #: RP1207
• Status: Withdrawn
• Phase: N/A
• First received: February 6, 2013
• Last updated: December 1, 2015
• Est. completion date: September 2017

Study information

• Verified date: December 2015
• Source: University of Western Ontario, Canada
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Food and Drug AdministrationNetherlands: Dutch Health Care InspectorateSpain: Ministry of Health
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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).

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease
• Inflammatory Bowel Diseases
• Ulcerative Colitis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Western Ontario, Canada

References & Publications (5)

Gisbert JP, Panés 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. Review. — View 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. — View 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. Epub 2006 Aug 22. — View 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. — View 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. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identification of patients at baseline that would benefit from receiving higher does of infliximab due to accelerated drug clearance		24 weeks	No
Primary	Pharmacokinetic Analysis of Infliximab in patients with moderate to severely active ulcerative colitis and Crohn's Disease	The primary objective of this study is to define the PK profile of IFX in patients with CD and UC and to determine covariates influencing drug clearance.	24 weeks	No
Secondary	Quantification of relative strengths of individual determinants of infliximab pharmacokinetics	Assessment of potential interactions between these determinants.	24 weeks	No